Calpain activation and cytoskeletal protein breakdown in the corpus callosum of head-injured patients

Calpain-mediated breakdown of the cytoskeleton has been proposed to contrib ute to brain damage resulting from head injury, We examined the corpus call osum from patients who died after a blunt head injury in order to determine if there was evidence of these pathophysiological events in a midline myel inated commissure that is susceptible to damage after human head injury. We stern blotting revealed marked reductions in the levels of neurofilament tr iplet proteins 200 and 68kDa in the corpus callosum of head-injured patient s compared with control subjects, Neurofilament 200kDa levels were signific antly reduced as detected by either phosphorylation-dependent or -independe nt antibodies, In contrast, there were minimal changes in the levels of bet a-tubulin or the microtubule-associated protein, tau, in the head-injured p atients, although amyloid precursor protein immunostaining demonstrated axo nal damage in 9 of the 10 patients, The inactive 80kDa and active 76kDa sub units of mu-calpain were present in control subjects and head-injured patie nts, However, there was a significant increase in the levels of calpain-med iated spectrin breakdown products in head-injured patients compared with th e control subjects, The results demonstrate that following human blunt head injury, there is a significant degradation of neurofilament proteins and i ncreased levels of calpain-mediated spectrin breakdown products within the corpus callosum, Therefore, our data support the hypothesis that calpain-me diated breakdown of the cytoskeleton may contribute to axonal damage after head injury.