Cyclosporin A limits calcium-induced axonal damage following traumatic brain injury

IN traumatic axonal injury, Ca2+ influx across a focally damaged axolemma p recipitates local mitochondrial failure, degradation of the subaxolemmal sp ectrin network and compaction of neurofilaments, which collectively contrib ute to axonal failure. In previous studies, cyclosporin A pretreatment pres erved mitochondrial integrity and attenuated axonal failure following traum a. Here we investigate whether this CsA-linked protection was related to th e concomitant blunting of intra-axonal, Ca2+-induced cytoskeletal changes i n traumatic axonal injury, assessed with antibodies targeting spectrin prot eolysis and neurofilament compaction. CsA pretreatment dramatically reduced Ca2+-induced cytoskeletal damage following injury; CsA-treated rats, compa red with vehicle-treated rats, displayed a 70% decrease in immunoreactive/d amaged profiles. We suggest that CsA-mediated preservation of mitochondrial integrity enables the restoration of ionic and metabolic homeostasis there by short-circuiting Ca2+-induced proteolysis in injured axons. (C) 1999 Lip pincott Williams & Wilkins.