Author(s): Büki A, Siman R, Trojanowski JQ, Povlishock JT
In animals and man, traumatic brain injury (TBI) results in axonal injury (AI) that contributes to morbidity and mortality. Such injured axons show progressive change leading to axonal disconnection. Although several theories implicate calcium in the pathogenesis of AI, experimental studies have failed to confirm its pivotal role. To explore the contribution of Ca2+-induced proteolysis to axonal injury, this study was undertaken in an animal model of TBI employing antibodies targeting both calpain-mediated spectrin proteolysis (CMSP) and focal neurofilament compaction (NFC), a marker of intra-axonal cytoskeletal perturbation, at 15-120 minutes (min) postinjury. Light microscopy (LM) revealed that TBI consistently evoked focal, intra-axonal CMSP that was spatially and temporally correlated with NFC. These changes were seen at 15 min postinjury with significantly increasing number of axons demonstrating CMSP immunoreactivity over time postinjury. Electron microscopy (EM) demonstrated that at 15 min postinjury CMSP was confined primarily to the subaxolemmal network. With increasing survival (30-120 min) CMSP filled the axoplasm proper. These findings provide the first direct evidence for focal CMSP in the pathogenesis of generalized/diffuse AI. Importantly, they also reveal an initial subaxolemmal involvement prior to induction of a more widespread axoplasmic change indicating a spatial-temporal compartmentalization of the calcium-induced proteolytic process that may be amenable to rapid therapeutic intervention.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/10218632
Author(s): Decuypere M, Klimo P Jr
Author(s): Blostein PA, Jones SJ, Buechler CM, Vandongen S
Author(s): Crevits L, Hanse MC, Tummers P, Van Maele G
Author(s): Bandtlow CE
Author(s): Brösamle C, Huber AB, Fiedler M, Skerra A, Schwab ME
Author(s): Mott TF, McConnon ML, Rieger BP
Author(s): McCrea M, Pliskin N, Barth J, Cox D, Fink J, et al.
Author(s): van Leeuwen N, Lingsma HF, Perel P, Lecky F, Roozenbeek B, et al.
Author(s): Zhou W, Xu D, Peng X, Zhang Q, Jia J, et al.
Author(s): Jager TE, Weiss HB, Coben JH, Pepe PE
Author(s): Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, et al.
Author(s): Bigler ED, Maxwell WL
Author(s): Königs M, de Kieviet JF, Oosterlaan J
Author(s): Rohling ML, Binder LM, Demakis GJ, Larrabee GJ, Ploetz DM, et al.
Author(s): Simmons AN, Matthews SC
Author(s): Panayiotou A, Jackson M, Crowe SF
Author(s): Caner H, Can A, Atalay B, Erdogan B, Albayrak AH, et al.
Author(s): Abu-Judeh HH, Parker R, Singh M, el-Zeftawy H, Atay S, et al.
Author(s): Atalay B, Caner H, Can A, Cekinmez M
Author(s): Tymianski M, Tator CH
Author(s): Abrous DN, Rodriguez J, le Moal M, Moser PC, Barnéoud P
Author(s): Büki A, Koizumi H, Povlishock JT
Author(s): Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, et al.
Author(s): Geddes JF, Vowles GH, Nicoll JA, Révész T
Author(s): Saatman KE, Zhang C, Bartus RT, McIntosh TK
Author(s): Posmantur R, Kampfl A, Siman R, Liu J, Zhao X, et al.
Author(s): Kampfl A, Posmantur R, Nixon R, Grynspan F, Zhao X, et al.
Author(s): Ercan M, Inci S, Kilinc K, Palaoglu S, Aypar U