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The traumatic axon injury (TAI) results from focal\nperturbations of the axolemma, allowing for calcium influx triggering local\nintraaxonal cytoskeletal and mitochondrial damage. This mitochondrial damage has \nbeen posited to cause local bioenergetic failure, leading to axonal failure and\ndisconnection; however, this mitochondrial damage may also lead to the release of\ncytochrome c (cyto-c), which then activates caspases with significant adverse\nintraaxonal consequences. In the current communication, we examine this\npossibility. Rats were subjected to TBI, perfused with aldehydes at 15-360 min\nafter injury, and processed for light microscopic (LM) and electron microscopic\n(EM) single-labeling immunohistochemistry to detect extramitochondrially\nlocalized cytochrome c (cyto-c) and the signature protein of caspase-3 activation\n(120 kDa breakdown product of alpha-spectrin) in TAI. Combinations of\ndouble-labeling fluorescent immunohistochemistry (D-FIHC) were also used to\ndemonstrate colocalization of calpain activation with cyto-c release and\ncaspase-3-induction. In foci of TAI qualitative-quantitative LM demonstrated a\nparallel, significant increase in cyto-c release and caspase-3 activation over\ntime after injury. EM analysis demonstrated that cyto-c and caspase-3\nimmunoreactivity were associated with mitochondrial swelling-disruption in sites \nof TAI. Furthermore, D-IFHC revealed a colocalization of calpain activation,\ncyto-c release, and caspase-3 induction in these foci, which also revealed\nprogressive TAI. The results demonstrate that cyto-c and caspase-3 participate in\nthe terminal processes of TAI. This suggests that those factors that play a role \nin the apoptosis in the neuronal soma are also major contributors to the demise\nof the axonal appendage.", "subjects" : [ { "otype" : "Classification", "mtid" : 12125, "link" : "/api/classification/12125", "label" : "Általános orvostudomány", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2009, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : true, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2024-03-08", "oaFree" : false, "citationCount" : 284, "citationCountUnpublished" : 0, "citationCountWoOther" : 275, "independentCitCountWoOther" : 226, "nationalOriginCitationCount" : 15, "foreignEditionCitationCount" : 264, "doiCitationCount" : 259, "wosCitationCount" : 249, "scopusCitationCount" : 268, "wosScopusCitationCount" : 275, "wosScopusCitationCountWoOther" : 275, 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