@article{MTMT:30581380,
	title = {Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment},
	url = {https://m2.mtmt.hu/api/publication/30581380},
	author = {Fülöp, Gábor Áron and Tarantini, Stefano and Yabluchanskiy, Andriy and Molnár, Andrea Ágnes and Prodan, Calin and Kiss, Tamás and Csípő, Tamás and Lipécz, Ágnes and Balasubramanian, Priya and Farkas, Eszter and Tóth, Péter József and Sorond, Farzaneh and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1152/ajpheart.00776.2018},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {316},
	unique-id = {30581380},
	issn = {0363-6135},
	abstract = {There has been an increasing appreciation of role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. The low pressure, low velocity and large volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.},
	keywords = {heart failure; venous circulation; Vascular cognitive impairment; microhemorrrhage},
	year = {2019},
	eissn = {1522-1539},
	pages = {H1124-H1140},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30646506,
	title = {Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice},
	url = {https://m2.mtmt.hu/api/publication/30646506},
	author = {Tarantini, Stefano and Valcarcel-Ares, Marta Noa and Tóth, Péter József and Yabluchanskiy, Andriy and Tucsek, Zsuzsanna and Kiss, Tamás and Hertelendy, Péter and Kinter, Michael and Ballabh, Praveen and Süle, Zoltán and Farkas, Eszter and Baur, Joseph A and Sinclair, David A and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1016/j.redox.2019.101192},
	journal-iso = {REDOX BIOL},
	journal = {REDOX BIOLOGY},
	volume = {24},
	unique-id = {30646506},
	issn = {2213-2317},
	abstract = {Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI).},
	keywords = {MICROCIRCULATION; endothelial dysfunction; ROS; Functional hyperemia; Oxidative stress},
	year = {2019},
	eissn = {2213-2317},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Süle, Zoltán/0000-0003-1304-0207; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30651188,
	title = {Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline},
	url = {https://m2.mtmt.hu/api/publication/30651188},
	author = {Valcarcel-Ares, Marta Noa and Tucsek, Zsuzsanna and Kiss, Tamás and Giles, Cory B. and Tarantini, Stefano and Yabluchanskiy, Andriy and Balasubramanian, Priya and Gautam, Tripti and Galvan, Veronica and Ballabh, Praveen and Richardson, Arlan and Freeman, Willard M. and Wren, Jonathan D. and Deak, Ferenc and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1093/gerona/gly127},
	journal-iso = {J GERONTOL A-BIOL MED SCI},
	journal = {JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES},
	volume = {74},
	unique-id = {30651188},
	issn = {1079-5006},
	abstract = {There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates bloodbrain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis that synergistic effects of obesity and aging on inflammatory processes exert deleterious effects on hippocampal function, young and aged C57BL/6 mice were rendered obese by chronic feeding of a high-fat diet followed by assessment of learning and memory function, measurement of hippocampal long-term potentiation (LTP), assessment of changes in hippocampal expression of genes relevant for synaptic function and determination of synaptic density. Because there is increasing evidence that altered production of lipid mediators modulate LTP, neuroinflammation and neurovascular coupling responses, the effects of obesity on hippocampal levels of relevant eicosanoid mediators were also assessed. We found that aging exacerbates obesity-induced microglia activation, which is associated with deficits in hippocampal-dependent learning and memory tests, impaired LTP, decreased synaptic density, and dysregulation of genes involved in regulation of synaptic plasticity. Obesity in aging also resulted in an altered hippocampal eicosanoid profile, including decreases in vasodilator and pro-LTP epoxy-eicosatrienoic acids (EETs). Collectively, our results taken together with previous findings suggest that obesity in aging promotes hippocampal inflammation, which in turn may contribute to synaptic dysfunction and cognitive impairment.},
	keywords = {metabolic syndrome; MILD COGNITIVE IMPAIRMENT; VCI; Vascular cognitive impairment; inflammaging},
	year = {2019},
	eissn = {1758-535X},
	pages = {290-298},
	orcid-numbers = {Kiss, Tamás/0000-0001-5339-5227; Tarantini, Stefano/0000-0001-5627-1430; Yabluchanskiy, Andriy/0000-0002-9648-7161; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30452332,
	title = {Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation},
	url = {https://m2.mtmt.hu/api/publication/30452332},
	author = {Fülöp, Gábor Áron and Kiss, Tamás and Tarantini, Stefano and Balasubramanian, Priya and Yabluchanskiy, Andriy and Farkas, Eszter and Bari, Ferenc and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1007/s11357-018-0047-6},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {40},
	unique-id = {30452332},
	issn = {2509-2715},
	abstract = {Aging-induced pro-inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promotes inflammation; however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypothesis that advanced aging promotes cellular senescence in the cerebral vasculature. We found that in cerebral arteries of 24-month-old mice, expression of molecular markers of senescence (p16(INK4a), p21) is upregulated as compared to that in young controls. Induction of senescence programs in cerebral arteries is associated by an upregulation of a wide range of inflammatory cytokines and chemokines, which are known to contribute to the senescence-associated secretory phenotype (SASP) in vascular cells. Age-related cerebrovascular senescence and inflammation are associated with neuroinflammation, as shown by the molecular footprint of microglia activation in the hippocampus. Genetic depletion of the pro-survival/anti-aging transcriptional regulator Nrf2 exacerbated age-related induction of senescence markers and inflammatory SASP factors and resulted in a heightened inflammatory status of the hippocampus. In conclusion, our studies provide evidence that aging and Nrf2 dysfunction promote cellular senescence in cerebral vessels, which may potentially cause or exacerbate age-related pathology.},
	keywords = {ENDOTHELIAL-CELLS; ACTIVATION; endothelial dysfunction; MOUSE MODEL; COGNITIVE IMPAIRMENT; SMOOTH-MUSCLE-CELLS; senescence; Vascular aging; Vascular cognitive impairment; SECRETORY PHENOTYPE; VASCULAR OXIDATIVE STRESS; AUTOREGULATORY DYSFUNCTION; IMPAIRS ANGIOGENIC CAPACITY},
	year = {2018},
	eissn = {2509-2723},
	pages = {513-521},
	orcid-numbers = {Kiss, Tamás/0000-0001-5339-5227; Tarantini, Stefano/0000-0001-5627-1430; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30306946,
	title = {PACAP deficiency as a model of aging.},
	url = {https://m2.mtmt.hu/api/publication/30306946},
	author = {Reglődi, Dóra and Atlasz, Tamás and Szabó, Edina and Jüngling, Adél and Tamás, Andrea and Juhász, Tamás and Fülöp, Balázs Dániel and Bardosi, A},
	doi = {10.1007/s11357-018-0045-8},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {40},
	unique-id = {30306946},
	issn = {2509-2715},
	abstract = {Dysregulation of neuropeptides may play an important role in aging-induced impairments. In the long list of neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) represents a highly effective cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. PACAP has neuro- and general cytoprotective effects due to anti-apoptotic, anti-inflammatory, and antioxidant actions. As PACAP is also a part of the endogenous protective machinery, it can be hypothesized that the decreased protective effects in lack of endogenous PACAP would accelerate age-related degeneration and PACAP knockout mice would display age-related degenerative signs earlier. Recent results support this hypothesis showing that PACAP deficiency mimics aspects of age-related pathophysiological changes including increased neuronal vulnerability and systemic degeneration accompanied by increased apoptosis, oxidative stress, and inflammation. Decrease in PACAP expression has been shown in different species from invertebrates to humans. PACAP-deficient mice display numerous pathological alterations mimicking early aging, such as retinal changes, corneal keratinization and blurring, and systemic amyloidosis. In the present review, we summarize these findings and propose that PACAP deficiency could be a good model of premature aging.},
	keywords = {APOPTOSIS; DEGENERATION; PACAP; Aging; amyloidosis},
	year = {2018},
	eissn = {2509-2723},
	pages = {437-452},
	orcid-numbers = {Atlasz, Tamás/0000-0002-8112-8633}
}

@article{MTMT:3413924,
	title = {Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype},
	url = {https://m2.mtmt.hu/api/publication/3413924},
	author = {Tarantini, Stefano and Valcarcel-Ares, MN and Yabluchanskiy, A and Tucsek, Z and Hertelendy, Péter and Kiss, Tamás and Gautam, T and Zhang, XA and Sonntag, WE and de Cabo, R and Farkas, Eszter and Elliott, MH and Kinter, MT and Deak, F and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1093/gerona/glx177},
	journal-iso = {J GERONTOL A-BIOL MED SCI},
	journal = {JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES},
	volume = {73},
	unique-id = {3413924},
	issn = {1079-5006},
	abstract = {Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2(+/+) and Nrf2(-/-), mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2(-/-) mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CAI area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.},
	keywords = {ALZHEIMERS-DISEASE; LONG-TERM POTENTIATION; high-fat diet; mouse somatosensory cortex; HIGH-FAT/SUCROSE DIET; Vascular cognitive impairment; Vascular cognitive impairment; Geriatrics & Gerontology; PRIMATE MACACA-MULATTA; AUTOREGULATORY DYSFUNCTION; RESVERATROL TREATMENT; CEREBROMICROVASCULAR ENDOTHELIAL-CELLS; Vascular contributions to cognitive impairment and dementia; ANTIOXIDANT RESPONSE},
	year = {2018},
	eissn = {1758-535X},
	pages = {853-863},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:3367042,
	title = {Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice},
	url = {https://m2.mtmt.hu/api/publication/3367042},
	author = {Tarantini, Stefano and Valcarcel-Ares, NM and Yabluchanskiy, A and Fülöp, Gábor Áron and Hertelendy, Péter and Gautam, T and Farkas, Eszter and Perz, A and Rabinovitch, PS and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1111/acel.12731},
	journal-iso = {AGING CELL},
	journal = {AGING CELL},
	volume = {17},
	unique-id = {3367042},
	issn = {1474-9718},
	year = {2018},
	eissn = {1474-9726},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30306956,
	title = {Repeated Valsalva maneuvers promote symptomatic manifestations of cerebral microhemorrhages. implications for the pathogenesis of vascular cognitive impairment in older adults},
	url = {https://m2.mtmt.hu/api/publication/30306956},
	author = {Ungvári, Zoltán István and Yabluchanskiy, Andriy and Tarantini, Stefano and Tóth, Péter József and Kirkpatrick, Angelia C and Csiszar, Anna and Prodan, Calin I},
	doi = {10.1007/s11357-018-0044-9},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {40},
	unique-id = {30306956},
	issn = {2509-2715},
	abstract = {Multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds"), which are associated with rupture of small intracerebral vessels, have been recognized as an important cause for cognitive decline in older adults. Although recent studies demonstrate that CMHs are highly prevalent in patients 65 and older, many aspects of the pathogenesis and clinical significance of CMHs remain obscure. In this longitudinal observational study, a case of a 77-year-old man with multifocal CMHs is described, in whom the rupture of intracerebral vessels could be linked to repeatedly performing extended Valsalva maneuvers. This patient was initially seen with acute aphasia after performing a prolonged Valsalva maneuver during underwater swimming. T2-weighted magnetic resonance imaging revealed a left acute frontal intracerebral hemorrhage (ICH) with multiple CMHs. The aphasia was resolved and no cognitive impairment was present. Two years later, he developed unsteadiness and confusion after performing two prolonged Valsalva maneuvers during underwater swimming separated by about 12 days. Repeat brain imaging revealed an acute right and a subacute left ICH, with a marked interval increase in the number of CMHs. The patient also exhibited manifest memory loss after the second admission and was diagnosed with dementia. These observations suggest that prolonged Valsalva maneuver is potentially a common precipitating cause of both CMHs and symptomatic ICHs. The Valsalva maneuver both increases the systolic arterial pressure and gives rise to a venous pressure wave transmitted to the brain in the absence of the competent antireflux jugular vein valves. This pressure increase is superimposed on existing hypertension and/or increases in blood pressure due to exercise and increased venous return due to immersion of the body in water. We advocate that further studies are needed to distinguish between CMHs with arterial and venous origins and their potential to lead to ICH induced by Valsalva maneuver as well as to determine whether these lesions have a predilection for a particular location.},
	keywords = {transient ischemic attack; stroke; Vascular aging; Cerebromicrovascular; Cerebrovascular; VCI; VCID; Vascular cognitive impairment; Vascular contributors to cognitive impairment and dementia},
	year = {2018},
	eissn = {2509-2723},
	pages = {485-496},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Tarantini, Stefano/0000-0001-5627-1430}
}

@article{MTMT:27339463,
	title = {Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer's disease and vascular cognitive impairment},
	url = {https://m2.mtmt.hu/api/publication/27339463},
	author = {Van, Skike Candice E and Jahrling, Jordan B and Olson, Angela B and Sayre, Naomi L and Hussong, Stacy A and Ungvári, Zoltán István and Lechleiter, James D and Galvan, Veronica},
	doi = {10.1152/ajpheart.00570.2017},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {314},
	unique-id = {27339463},
	issn = {0363-6135},
	year = {2018},
	eissn = {1522-1539},
	pages = {H693-H703},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30452359,
	title = {IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan},
	url = {https://m2.mtmt.hu/api/publication/30452359},
	author = {Ashpole, Nicole M. and Logan, Sreemathi and Yabluchanskiy, Andriy and Mitschelen, Matthew C. and Yan, Han and Farley, Julie A. and Hodges, Erik L. and Ungvári, Zoltán István and Csiszar, Anna and Chen, Sixia and Georgescu, Constantin and Hubbard, Gene B. and Ikeno, Yuji and Sonntag, William E.},
	doi = {10.1007/s11357-017-9971-0},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {39},
	unique-id = {30452359},
	issn = {2509-2715},
	abstract = {Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf(f/f) C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.},
	keywords = {CANCER; LONGEVITY; INSULIN; Aging; BODY-COMPOSITION; somatomedin C; GROWTH-FACTOR-I; hormone deficiency; Insulin-like Growth Factor-1; Human longevity; FATAL NEOPLASTIC DISEASES; DELAYED OCCURRENCE; DWARF MICE; Oxidative stress},
	year = {2017},
	eissn = {2509-2723},
	pages = {129-145},
	orcid-numbers = {Yabluchanskiy, Andriy/0000-0002-9648-7161; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:27060498,
	title = {Hypertension impairs neurovascular coupling and promotes microvascular injury: role in exacerbation of Alzheimer's disease},
	url = {https://m2.mtmt.hu/api/publication/27060498},
	author = {Csiszar, Anna and Tarantini, Stefano and Fülöp, Gábor Áron and Kiss, Tamás and Valcarcel-Ares, M Noa and Galvan, Veronica and Ungvári, Zoltán István and Yabluchanskiy, Andriy},
	doi = {10.1007/s11357-017-9991-9},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {39},
	unique-id = {27060498},
	issn = {2509-2715},
	abstract = {Hypertension in the elderly substantially increases both the risk of vascular cognitive impairment (VCI) and Alzheimer's disease (AD); however, the underlying mechanisms are not completely understood. This review discusses the effects of hypertension on structural and functional integrity of cerebral microcirculation, including hypertension-induced alterations in neurovascular coupling responses, cellular and molecular mechanisms involved in microvascular damage (capillary rarefaction, blood-brain barrier disruption), and the genesis of cerebral microhemorrhages and their potential role in exacerbation of cognitive decline associated with AD. Understanding and targeting the hypertension-induced cerebromicrovascular alterations that are involved in the onset and progression of AD and contribute to cognitive impairment are expected to have a major role in preserving brain health in high-risk older individuals.},
	keywords = {MICROCIRCULATION; HYPERTENSION; endothelial dysfunction; Angiotensin II; BLOOD-BRAIN-BARRIER; MILD COGNITIVE IMPAIRMENT; High blood pressure; Neurovascular coupling; mouse somatosensory cortex; VCID; WHITE-MATTER HYPERINTENSITIES; CEREBRAL AMYLOID ANGIOPATHY; PRIMATE MACACA-MULATTA; VASCULAR OXIDATIVE STRESS; OXYGEN SPECIES MEDIATE; CEREBROMICROVASCULAR ENDOTHELIAL-CELLS; Functional hyperemia},
	year = {2017},
	eissn = {2509-2723},
	pages = {359-372},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:3235445,
	title = {Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer's disease using functional laser speckle contrast imaging.},
	url = {https://m2.mtmt.hu/api/publication/3235445},
	author = {Tarantini, Stefano and Fülöp, Gábor Áron and Kiss, Tamás and Farkas, Eszter and Zölei-Szénási, Dániel and Galvan, V and Tóth, Péter József and Csiszar, Anna and Ungvári, Zoltán István and Yabluchanskiy, A},
	doi = {10.1007/s11357-017-9980-z},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {39},
	unique-id = {3235445},
	issn = {2509-2715},
	abstract = {Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia ("neurovascular uncoupling"). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses. Laser speckle contrast imaging (LSCI) is a technique that allows rapid and minimally invasive visualization of changes in regional cerebromicrovascular blood perfusion. This type of imaging technique combines high resolution and speed to provide great spatiotemporal accuracy to measure moment-to-moment changes in cerebral blood flow induced by neuronal activation. Here, we provide detailed protocols for the successful measurement in neurovascular coupling responses in anesthetized mice equipped with a thinned-skull cranial window using LSCI. This method can be used to evaluate the effects of anti-aging or anti-AD treatments on cerebromicrovascular health.},
	keywords = {Neurovascular coupling; LASCA; laser speckle contrast imaging; Functional hyperemia; Laser speckle contrast analysis; Laser speckle imaging; LSI},
	year = {2017},
	eissn = {2509-2723},
	pages = {465-473},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:3331464,
	title = {Insulin-like growth factor 1 deficiency exacerbates hypertension-induced cerebral microhemorrhages in mice, mimicking the aging phenotype.},
	url = {https://m2.mtmt.hu/api/publication/3331464},
	author = {Tarantini, Stefano and Valcarcel-Ares, NM and Yabluchanskiy, A and Springó, Zsolt and Fülöp, Gábor Áron and Ashpole, N and Gautam, T and Giles, CB and Wren, JD and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1111/acel.12583},
	journal-iso = {AGING CELL},
	journal = {AGING CELL},
	volume = {16},
	unique-id = {3331464},
	issn = {1474-9718},
	abstract = {Clinical and experimental studies show that aging exacerbates hypertension-induced cerebral microhemorrhages (CMHs), which progressively impair neuronal function. There is growing evidence that aging promotes insulin-like growth factor 1 (IGF-1) deficiency, which compromises multiple aspects of cerebromicrovascular and brain health. To determine the role of IGF-1 deficiency in the pathogenesis of CMHs, we induced hypertension in mice with liver-specific knockdown of IGF-1 (Igf1(f/f) + TBG-Cre-AAV8) and control mice by angiotensin II plus l-NAME treatment. In IGF-1-deficient mice, the same level of hypertension led to significantly earlier onset and increased incidence and neurological consequences of CMHs, as compared to control mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Previous studies showed that in aging, increased oxidative stress-mediated matrix metalloprotease (MMP) activation importantly contributes to the pathogenesis of CMHs. Thus, it is significant that hypertension-induced cerebrovascular oxidative stress and MMP activation were increased in IGF-1-deficient mice. We found that IGF-1 deficiency impaired hypertension-induced adaptive media hypertrophy and extracellular matrix remodeling, which together with the increased MMP activation likely also contributes to increased fragility of intracerebral arterioles. Collectively, IGF-1 deficiency promotes the pathogenesis of CMHs, mimicking the aging phenotype, which likely contribute to its deleterious effect on cognitive function. Therapeutic strategies that upregulate IGF-1 signaling in the cerebral vessels and/or reduce microvascular oxidative stress, and MMP activation may be useful for the prevention of CMHs, protecting cognitive function in high-risk elderly patients.},
	keywords = {Animals; Male; MICE; PHENOTYPE; Mice, Inbred C57BL; Psychomotor performance; Mice, Transgenic; Disease Models, Animal; Gait; Infusion Pumps, Implantable; Aging/*metabolism/pathology; Matrix Metalloproteinases/genetics/metabolism; Extracellular Matrix/*metabolism/pathology; NG-Nitroarginine Methyl Ester/administration & dosage; Insulin-Like Growth Factor I/*deficiency/genetics; Hypertension/chemically induced/complications/*metabolism/physiopathology; Cerebral Hemorrhage/chemically induced/etiology/*metabolism/physiopathology; Angiotensin II/administration & dosage; Oxidative stress},
	year = {2017},
	eissn = {1474-9726},
	pages = {469-479},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:27241039,
	title = {Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline},
	url = {https://m2.mtmt.hu/api/publication/27241039},
	author = {Tarantini, Stefano and Tran, Cam Ha T and Gordon, Grant R and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1016/j.exger.2016.11.004},
	journal-iso = {EXP GERONTOL},
	journal = {EXPERIMENTAL GERONTOLOGY},
	volume = {94},
	unique-id = {27241039},
	issn = {0531-5565},
	year = {2017},
	eissn = {1873-6815},
	pages = {52-58},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:30452345,
	title = {Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice},
	url = {https://m2.mtmt.hu/api/publication/30452345},
	author = {Tarantini, Stefano and Yabluchanksiy, Andriy and Fülöp, Gábor Áron and Hertelendy, Péter and Valcarcel-Ares, M. Noa and Kiss, Tamás and Bagwell, Jonathan M. and O'Connor, Daniel and Farkas, Eszter and Sorond, Farzaneh and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1007/s11357-017-0003-x},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {39},
	unique-id = {30452345},
	issn = {2509-2715},
	abstract = {There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To establish a direct cause-andeffect relationship between impaired NVC and gait abnormalities, we induced neurovascular uncoupling pharmacologically in young C57BL/6 mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor MSPPOH, the NO synthase inhibitor L-NAME, and the COX inhibitor indomethacin significantly decreased NVC mimicking the aging phenotype. Pharmacologically induced neurovascular uncoupling significantly decreased the dynamic gait parameter duty cycle, altered footfall patterns, and significantly increased phase dispersion, indicating impaired interlimb coordination. Impaired NVC also tended to increase gait variability. Thus, selective experimental disruption of NVC causes subclinical gait abnormalities, supporting the importance of CBF in both cognitive function and gait regulation.},
	keywords = {ALZHEIMERS-DISEASE; TYPE-2 DIABETES-MELLITUS; CEREBRAL-BLOOD-FLOW; Gait; Neurovascular coupling; mouse somatosensory cortex; VASCULAR CONTRIBUTIONS; AUTOREGULATORY DYSFUNCTION; Catwalk; PREDICTS COGNITIVE DECLINE; FUNCTIONING OLDER-ADULTS; MOBILIZE BOSTON},
	year = {2017},
	eissn = {2509-2723},
	pages = {601-614},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:3139193,
	title = {Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging},
	url = {https://m2.mtmt.hu/api/publication/3139193},
	author = {Tóth, Péter József and Tarantini, Stefano and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1152/ajpheart.00581.2016},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {312},
	unique-id = {3139193},
	issn = {0363-6135},
	abstract = {Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined.},
	keywords = {NITRIC-OXIDE SYNTHASE; MICROCIRCULATION; physiology; AGE-RELATED-CHANGES; Constriction; stroke; Alzheimer's disease; SPONTANEOUSLY HYPERTENSIVE-RATS; GROWTH-FACTOR-I; BLOOD-BRAIN-BARRIER; Cerebral circulation; Vascular aging; Neurovascular coupling; Cerebrovascular; Cardiac & Cardiovascular Systems; SMALL VESSEL DISEASE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; MITOCHONDRIAL OXIDATIVE STRESS; Functional hyperemia; myogenic; CORTICAL SPREADING DEPOLARIZATION},
	year = {2017},
	eissn = {1522-1539},
	pages = {H1-H20},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:27059368,
	title = {Hypertension-induced synapse loss and impairment in synaptic plasticity in the mouse hippocampus mimics the aging phenotype: implications for the pathogenesis of vascular cognitive impairment},
	url = {https://m2.mtmt.hu/api/publication/27059368},
	author = {Tucsek, Zsuzsanna and Valcarcel-Ares, M Noa and Tarantini, Stefano and Yabluchanskiy, Andriy and Fülöp, Gábor Áron and Gautam, Tripti and Orock, Albert and Csiszar, Anna and Deak, Ferenc and Ungvári, Zoltán István},
	doi = {10.1007/s11357-017-9981-y},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {39},
	unique-id = {27059368},
	issn = {2509-2715},
	abstract = {Strong epidemiological and experimental evidence indicates that hypertension has detrimental effects on the cerebral microcirculation and thereby promotes accelerated brain aging. Hypertension is an independent risk factor for both vascular cognitive impairment (VCI) and Alzheimer's disease (AD). However, the pathophysiological link between hypertension-induced cerebromicrovascular injury (e.g., blood-brain barrier disruption, increased microvascular oxidative stress, and inflammation) and cognitive decline remains elusive. The present study was designed to characterize neuronal functional and morphological alterations induced by chronic hypertension and compare them to those induced by aging. To achieve that goal, we induced hypertension in young C57BL/6 mice by chronic (4 weeks) infusion of angiotensin II. We found that long-term potentiation (LTP) of performant path synapses following high-frequency stimulation of afferent fibers was decreased in hippocampal slices obtained from hypertensive mice, mimicking the aging phenotype. Hypertension and advanced age were associated with comparable decline in synaptic density in the stratum radiatum of the mouse hippocampus. Hypertension, similar to aging, was associated with changes in mRNA expression of several genes involved in regulation of neuronal function, including down-regulation of Bdnf, Homer1, and Dlg4, which may have a role in impaired synaptic plasticity. Collectively, hypertension impairs synaptic plasticity, reduces synaptic density, and promotes dysregulation of genes involved in synaptic function in the mouse hippocampus mimicking the aging phenotype. These hypertension-induced neuronal alterations may impair establishment of memories in the hippocampus and contribute to the pathogenesis and clinical manifestation of both vascular cognitive impairment (VCI) and Alzheimer's disease (AD).},
	keywords = {Blood Pressure; Inflammation; ANGIOTENSIN-II; ALZHEIMERS-DISEASE; MICROCIRCULATION; AGE-RELATED-CHANGES; HYPERTENSION; LONG-TERM POTENTIATION; GROWTH-FACTOR-I; Vascular aging; CA1 region; IGF-1 DEFICIENCY; LEWIS DWARF RATS; Oxidative stress},
	year = {2017},
	eissn = {2509-2723},
	pages = {385-406},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:3270817,
	title = {Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence},
	url = {https://m2.mtmt.hu/api/publication/3270817},
	author = {Ungvári, Zoltán István and Tarantini, Stefano and Hertelendy, Péter and Valcarcel-Ares, MN and Fülöp, Gábor Áron and Logan, S and Kiss, Tamás and Farkas, Eszter and Csiszar, Anna and Yabluchanskiy, A},
	doi = {10.1007/s11357-017-9964-z},
	journal-iso = {GEROSCIENCE},
	journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)},
	volume = {39},
	unique-id = {3270817},
	issn = {2509-2715},
	abstract = {Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due gamma- irradiation-induced cerebromicrovascular injury. Moment-to-moment adjustment of cerebral blood flow (CBF) vi a neuronal activity-dependent cerebromicrovascular dilation (functional hyperemia) has a critical role inmaintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associates with impaired cerebromicrovascular function, C56BL.6mice (3months) subjected to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks) and control mice were compared. Mice were tested for spatial memory performance (radial arm water maze), sensorimotor coordination (computerized gait analysis, CatWalk), and cerebromicrovascular function (whisker- stimulation-induced increases in CBF, measured by laser Doppler flowmetry) at 3 to 6 months post-irradiation. We found that mice with WBI exhibited impaired cerebromicrovascular function at 3 months post-irradiation, which was associated with impaired performance in the radial arm water maze. At 6 months, post-irradiation progressive impairment in gait coordination (including changes in the regularity index and phase dispersion) was also evident. Collectively, our findings provide evidence for early and persisting neurovascular impairment after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment.},
	keywords = {DEMENTIA; DNA Damage; cellular senescence; Neurovascular coupling; Neurovascular unit; Functional hyperemia; Whole brain irradiation; Gait dysfunction},
	year = {2017},
	eissn = {2509-2723},
	pages = {33-42},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Tarantini, Stefano/0000-0001-5627-1430; Kiss, Tamás/0000-0001-5339-5227; Farkas, Eszter/0000-0002-8478-9664}
}

@article{MTMT:26771441,
	title = {Cerebral microhemorrhages: mechanisms, consequences, and prevention},
	url = {https://m2.mtmt.hu/api/publication/26771441},
	author = {Ungvári, Zoltán István and Tarantini, Stefano and Kirkpatrick, Angelia C and Csiszar, Anna and Prodan, Calin I},
	doi = {10.1152/ajpheart.00780.2016},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {312},
	unique-id = {26771441},
	issn = {0363-6135},
	abstract = {The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes, and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs. CMHs are also now recognized by the National Institutes of Health as a major factor in Alzheimer's disease pathology. Moreover, the presence of CMHs is an independent risk factor for subsequent larger intracerebral hemorrhages. In this article, we review the epidemiology, detection, risk factors, clinical significance, and pathogenesis of CMHs. The potential age-related cellular mechanisms underlying the development of CMHs are discussed, with a focus on the structural determinants of microvascular fragility, age-related alterations in cerebrovascular adaptation to hypertension, the role of oxidative stress and matrix metalloproteinase activation, and the deleterious effects of arterial stiffening, increased pulse pressure, and impaired myogenic autoregulatory protection on the brain microvasculature. Finally, we examine potential treatments for the prevention of CMHs based on the proposed model of agingand hypertension-dependent activation of the reactive oxygen species-matrix metalloproteinases axis, and we discuss critical questions to be addressed by future studies.},
	keywords = {physiology; stroke; SPONTANEOUSLY HYPERTENSIVE-RATS; SMOOTH-MUSCLE-CELLS; BLOOD-BRAIN-BARRIER; Vascular aging; Cerebromicrovascular; Cerebrovascular; Vascular cognitive impairment; Vascular contributors to cognitive impairment and dementia; Cardiac & Cardiovascular Systems; SMALL VESSEL DISEASE; WHITE-MATTER HYPERINTENSITIES; VASCULAR OXIDATIVE STRESS; CEREBROMICROVASCULAR ENDOTHELIAL-CELLS; IMPAIRS ANGIOGENIC CAPACITY; RECURRENT INTRACEREBRAL HEMORRHAGE},
	year = {2017},
	eissn = {1522-1539},
	pages = {H1128-H1143},
	orcid-numbers = {Ungvári, Zoltán István/0000-0002-6035-6039; Tarantini, Stefano/0000-0001-5627-1430}
}

@article{MTMT:26002092,
	title = {Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet},
	url = {https://m2.mtmt.hu/api/publication/26002092},
	author = {Bernier, Michel and Wahl, Devin and Ali, Ahmed and Allard, Joanne and Faulkner, Shakeela and Wnorowski, Artur and Sanghvi, Mitesh and Moaddel, Ruin and Alfaras, Irene and Mattison, Julie A and Tarantini, Stefano and Tucsek, Zsuzsanna and Ungvári, Zoltán István and Csiszar, Anna and Pearson, Kevin J and de Cabo, Rafael},
	doi = {10.18632/aging.100942},
	journal-iso = {AGING-US},
	journal = {AGING-US},
	volume = {8},
	unique-id = {26002092},
	issn = {1945-4589},
	year = {2016},
	eissn = {1945-4589},
	pages = {899-916},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Ungvári, Zoltán István/0000-0002-6035-6039; de Cabo, Rafael/0000-0002-3354-2442}
}

@article{MTMT:2903149,
	title = {Pharmacologically-induced neurovascular uncoupling is associated with cognitive impairment in mice},
	url = {https://m2.mtmt.hu/api/publication/2903149},
	author = {Tarantini, Stefano and Hertelendy, Péter and Tucsek, Z and Valcarcel-Ares, M N and Smith, N and Menyhárt, Ákos and Farkas, Eszter and Hodges, E and Towner, R and Deak, F and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István and Tóth, Péter József},
	doi = {10.1038/jcbfm.2015.162},
	journal-iso = {J CEREBR BLOOD F MET},
	journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM},
	volume = {35},
	unique-id = {2903149},
	issn = {0271-678X},
	year = {2015},
	eissn = {1559-7016},
	pages = {1871-1881},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Menyhárt, Ákos/0000-0002-1355-3208; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2798905,
	title = {Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection},
	url = {https://m2.mtmt.hu/api/publication/2798905},
	author = {Tóth, Péter József and Tarantini, Stefano and Springó, Zsolt and Tucsek, Z and Gautam, T and Giles, CB and Wren, JD and Koller, Ákos and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1111/acel.12315},
	journal-iso = {AGING CELL},
	journal = {AGING CELL},
	volume = {14},
	unique-id = {2798905},
	issn = {1474-9718},
	abstract = {Recent studies demonstrate that aging exacerbates hypertension-induced cognitive decline, but the specific age-related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension-induced CMHs young (3months) and aged (24months) mice were treated with angiotensin II plus L-NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension-induced cerebrovascular oxidative stress and redox-sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension-induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension-induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high-risk elderly patients.},
	keywords = {ANGIOTENSIN-II; LIFE-SPAN; ACTIVATION; DEMENTIA; Cognitive function; NADPH OXIDASE; NADPH OXIDASE; endothelial function; Arteriole; CELL BIOLOGY; Microbleed; NAD(P)H OXIDASE; Microbleeds; MITOCHONDRIAL OXIDATIVE STRESS; Oxidative stress},
	year = {2015},
	eissn = {1474-9726},
	pages = {400-408},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2920558,
	title = {IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging},
	url = {https://m2.mtmt.hu/api/publication/2920558},
	author = {Tóth, Péter József and Tarantini, Stefano and Ashpole, NM and Tucsek, Z and Milne, GL and Valcarcel-Ares, NM and Menyhárt, Ákos and Farkas, Eszter and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1111/acel.12372},
	journal-iso = {AGING CELL},
	journal = {AGING CELL},
	volume = {14},
	unique-id = {2920558},
	issn = {1474-9718},
	abstract = {Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1f/f -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment.},
	keywords = {NITRIC-OXIDE SYNTHASE; CEREBRAL-BLOOD-FLOW; AGE-RELATED-CHANGES; somatomedin C; endothelial dysfunction; nitric oxide; GROWTH-FACTOR-I; CELL BIOLOGY; ASTROCYTE; Insulin-like Growth Factor-1; Vascular aging; mouse somatosensory cortex; AMES DWARF MICE; VASCULAR OXIDATIVE STRESS; Functional hyperemia; arachidonic acid metabolites; neurovascular uncoupling; WHISKER BARREL CORTEX; VIBRISSAL STIMULATION},
	year = {2015},
	eissn = {1474-9726},
	pages = {1034-1044},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Menyhárt, Ákos/0000-0002-1355-3208; Farkas, Eszter/0000-0002-8478-9664; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:25859074,
	title = {Resveratrol Prevents High Fat/Sucrose Diet-Induced Central Arterial Wall Inflammation and Stiffening in Nonhuman Primates},
	url = {https://m2.mtmt.hu/api/publication/25859074},
	author = {Mattison, Julie A and Wang, Mingyi and Bernier, Michel and Zhang, Jing and Park, Sung-Soo and Maudsley, Stuart and An, Steven S and Santhanam, Lakshmi and Martin, Bronwen and Faulkner, Shakeela and Morrell, Christopher and Baur, Joseph A and Peshkin, Leonid and Sosnowska, Danuta and Csiszar, Anna and Herbert, Richard L and Tilmont, Edward M and Ungvári, Zoltán István and Pearson, Kevin J and Lakatta, Edward G and de Cabo, Rafael},
	doi = {10.1016/j.cmet.2014.04.018},
	journal-iso = {CELL METAB},
	journal = {CELL METABOLISM},
	volume = {20},
	unique-id = {25859074},
	issn = {1550-4131},
	year = {2014},
	eissn = {1932-7420},
	pages = {183-190},
	orcid-numbers = {Bernier, Michel/0000-0002-5948-368X; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2496231,
	title = {Resveratrol treatment rescues neurovascular coupling in aged mice: role of improved cerebromicrovascular endothelial function and downregulation of NADPH oxidase},
	url = {https://m2.mtmt.hu/api/publication/2496231},
	author = {Tóth, Péter József and Tarantini, Stefano and Tucsek, Zsuzsanna and Ashpole, NM and Sosnowska, D and Gautam, T and Ballabh, P and Koller, Ákos and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1152/ajpheart.00744.2013},
	journal-iso = {AM J PHYSIOL HEART C},
	journal = {AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY},
	volume = {306},
	unique-id = {2496231},
	issn = {0363-6135},
	abstract = {Moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is essential for the maintenance of normal neuronal function. Increased oxidative stress that occurs with aging was shown to impair neurovascular coupling, which likely contributes to a significant age-related decline in higher brain function, increasing the risk for vascular cognitive impairment (VCI). Resveratrol is a polyphenolic compound that exerts significant anti-aging protective effects in large vessels but its effects on the cerebromicrovasculature remain poorly defined. The present study was undertaken to investigate the capacity of resveratrol to improve neurovascular coupling in aging. In aged (24 months old) C57BL/6 mice L-NAME sensitive, NO-mediated CBF responses to whisker stimulation and to the endothelium-dependent dilator acethylcholine (ACh) were impaired as compared to those in young (3 months old) mice. Treatment of aged mice with resveratrol rescued neurovascular coupling and ACh-induced responses, which was associated with down-regulation of cortical expression of NADPH oxidase and decreased levels of biomarkers of oxidative/nitrative stress (3-nitrotyrosine, 8-isoprostanes). Resveratrol also attenuated age-related increases in ROS production in cultured cerebromicrovascular endothelial cells (DCF fluorescence, flow cytometry). In conclusion, treatment with resveratrol rescues cortical neurovascular coupling responses to increased neuronal activity in aged mice, likely by restoring cerebromicrovascular endothelial function via down-regulation of NADPH-oxidase derived ROS production. Beneficial cerebromicrovascular effects of resveratrol likely contribute to its protective effects on higher brain function in aging.},
	year = {2014},
	eissn = {1522-1539},
	pages = {H299-H308},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2701735,
	title = {Aging Exacerbates Obesity-induced Cerebromicrovascular Rarefaction, Neurovascular Uncoupling, and Cognitive Decline in Mice.},
	url = {https://m2.mtmt.hu/api/publication/2701735},
	author = {Tucsek, Z and Tóth, Péter József and Tarantini, Stefano and Sosnowska, D and Gautam, T and Warrington, JP and Giles, CB and Wren, JD and Koller, Ákos and Ballabh, P and Sonntag, WE and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1093/gerona/glu080},
	journal-iso = {J GERONTOL A-BIOL MED SCI},
	journal = {JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES},
	volume = {69},
	unique-id = {2701735},
	issn = {1079-5006},
	abstract = {Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet-fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood-brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging.},
	year = {2014},
	eissn = {1758-535X},
	pages = {1339-1352},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2496237,
	title = {Obesity in Aging Exacerbates Blood-Brain Barrier Disruption, Neuroinflammation, and Oxidative Stress in the Mouse Hippocampus: Effects on Expression of Genes Involved in Beta-Amyloid Generation and Alzheimer's Disease.},
	url = {https://m2.mtmt.hu/api/publication/2496237},
	author = {Tucsek, Z and Tóth, Péter József and Sosnowska, D and Gautam, T and Mitschelen, M and Koller, Ákos and Szalai, Gábor and Sonntag, WE and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1093/gerona/glt177},
	journal-iso = {J GERONTOL A-BIOL MED SCI},
	journal = {JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES},
	volume = {69},
	unique-id = {2496237},
	issn = {1079-5006},
	abstract = {There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet-fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflammation and blood-brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood-brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein-dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals.},
	year = {2014},
	eissn = {1758-535X},
	pages = {1212-1226},
	orcid-numbers = {Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:2381966,
	title = {Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension.},
	url = {https://m2.mtmt.hu/api/publication/2381966},
	author = {Tóth, Péter József and Tucsek, Zsuzsanna and Sosnowska, D and Gautam, T and Mitschelen, M and Tarantini, Stefano and Deák, Ferenc and Koller, Ákos and Sonntag, WE and Csiszar, Anna and Ungvári, Zoltán István},
	doi = {10.1038/jcbfm.2013.143},
	journal-iso = {J CEREBR BLOOD F MET},
	journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM},
	volume = {33},
	unique-id = {2381966},
	issn = {0271-678X},
	abstract = {Hypertension in the elderly substantially contributes to cerebromicrovascular damage and promotes the development of vascular cognitive impairment. Despite the importance of the myogenic mechanism in cerebromicrovascular protection, it is not well understood how aging affects the functional adaptation of cerebral arteries to high blood pressure. Hypertension was induced in young (3 months) and aged (24 months) C57/BL6 mice by chronic infusion of angiotensin II (AngII). In young hypertensive mice, the range of cerebral blood flow autoregulation was extended to higher pressure values, and the pressure-induced tone of middle cerebral artery (MCA) was increased. In aged hypertensive mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In young mice, the mechanism of adaptation to hypertension involved upregulation of the 20-HETE (20-hydroxy-5,8,11,14-eicosatetraenoic acid)/transient receptor potential cation channel, subfamily C (TRPC6) pathway and this mechanism was impaired in aged hypertensive mice. Downstream consequences of cerebrovascular autoregulatory dysfunction in aged AngII-induced hypertensive mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal dependent cognitive function. Collectively, aging impairs autoregulatory protection in the brain of mice with AngII-induced hypertension, potentially exacerbating cerebromicrovascular injury and neuroinflammation.Journal of Cerebral Blood Flow & Metabolism advance online publication, 14 August 2013; doi:10.1038/jcbfm.2013.143.},
	year = {2013},
	eissn = {1559-7016},
	pages = {1732-1742},
	orcid-numbers = {Tarantini, Stefano/0000-0001-5627-1430; Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}

@article{MTMT:1827543,
	title = {Liver-Specific Knockdown of IGF-1 Decreases Vascular Oxidative Stress Resistance by Impairing the Nrf2-Dependent Antioxidant Response: A Novel Model of Vascular Aging},
	url = {https://m2.mtmt.hu/api/publication/1827543},
	author = {Bailey-Downs, LC and Mitschelen, M and Sosnowska, D and Tóth, Péter József and Pinto, JT and Ballabh, P and Valcarcel-Ares, MN and Farley, J and Koller, Ákos and Henthorn, JC and Bass, C and Sonntag, WE and Ungvári, Zoltán István and Csiszar, Anna},
	doi = {10.1093/gerona/glr164},
	journal-iso = {J GERONTOL A-BIOL MED SCI},
	journal = {JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES},
	volume = {67},
	unique-id = {1827543},
	issn = {1079-5006},
	year = {2012},
	eissn = {1758-535X},
	pages = {313-329},
	orcid-numbers = {Koller, Ákos/0000-0003-3256-8701; Ungvári, Zoltán István/0000-0002-6035-6039}
}