(EKÖP-2024–2) Támogató: New National Excellence Program
Chemotherapy-related cognitive impairment, commonly referred to as "chemobrain," significantly
affects cancer survivors' quality of life, yet its underlying mechanisms remain unclear.
Most chemotherapeutic agents cannot cross the blood-brain barrier (BBB), yet they
cause central nervous system side effects, suggesting alternative pathways of toxicity.
Given that these drugs interact with the cerebrovascular endothelium at their highest
concentrations, it is logical to hypothesize that endothelial damage contributes to
these effects. Our recent studies demonstrated that paclitaxel-induced cognitive impairment
in a mouse model results in a partial BBB disruption and subsequent neuroinflammation,
mediated by chemotherapy-induced endothelial senescence. In this pilot study, we used
two-photon microscopy to assess BBB permeability in mice receiving a clinically relevant
cisplatin regimen, evaluating the leakage of fluorescent dextran tracers of varying
molecular weights. Two months post-treatment, cisplatin-treated mice exhibited significantly
increased BBB permeability to smaller molecular tracers (40 kDa, 3 kDa, and 0.3 kDa)
compared to controls, indicating sustained BBB disruption. These results align with
our findings for paclitaxel and suggest that chemotherapy-induced endothelial damage
and senescence play a central role in cognitive impairments. Interventions targeting
endothelial health could mitigate these long-term effects, improving cognitive outcomes
for cancer survivors.
