Calpain activation and cytoskeletal protein breakdown in the corpus callosum of head-injured patients.
Calpain-mediated breakdown of the cytoskeleton has been proposed to contribute to brain damage resulting from head injury. We examined the corpus callosum from patients who died after a blunt head injury in order to determine if there was evidence of these pathophysiological events in a midline myelinated commissure that is susceptible to damage after human head injury. Western blotting revealed marked reductions in the levels of neurofilament triplet proteins 200 and 68kDa in the corpus callosum of head-injured patients compared with control subjects. Neurofilament 200kDa levels were significantly reduced as detected by either phosphorylation-dependent or -independent antibodies. In contrast, there were minimal changes in the levels of beta-tubulin or the microtubule-associated protein, tau, in the head-injured patients, although amyloid precursor protein immunostaining demonstrated axonal damage in 9 of the 10 patients. The inactive 800kDa and active 76kDa subunits of mu-calpain were present in control subjects and head-injured patients. However, there was a significant increase in the levels of calpain-mediated spectrin breakdown products in head-injured patients compared with the control subjects. The results demonstrate that following human blunt head injury, there is a significant degradation of neurofilament proteins and increased levels of calpain-mediated spectrin breakdown products within the corpus callosum. Therefore, our data support the hypothesis that calpain-mediated breakdown of the cytoskeleton may contribute to axonal damage after head injury.
McCracken
E
E
Wellcome Surgical Institute & Hugh Fraser Laboratories, University of Glasgow, UK.
Hunter
A J
AJ
Patel
S
S
Graham
D I
DI
Dewar
D
D
D000328:Adult; D000368:Aged; D002154:Calpain / Q000378:metabolism*; D003337:Corpus Callosum / Q000378:metabolism*; D006259:Craniocerebral Trauma / Q000378:metabolism* / Q000503:physiopathology; D020833:Diffuse Axonal Injury / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism*
D016900:Neurofilament Proteins; C066858:neurofilament protein NF 68; C051774:neurofilament protein H; D002154:Calpain