A calpain inhibitor attenuates cortical cytoskeletal protein loss after experimental traumatic brain injury in the rat

Author(s): Posmantur R, Kampfl A, Siman R, Liu J, Zhao X, et al.


The capacity of a calpain inhibitor to reduce losses of neurofilament 200-, neurofilament 68- and calpain 1-mediated spectrin breakdown products was examined following traumatic brain injury in the rat. Twenty-four hours after unilateral cortical impact injury, western blot analyses detected neurofilament 200 losses of 65% (ipsilateral) and 36% (contralateral) of levels observed in naive, uninjured rat cortices. Neurofilament 68 protein levels decreased only in the ipsilateral cortex by 35% relative to naive protein levels. Calpain inhibitor 2, administered 10 min after injury via continuous arterial infusion into the right external carotid artery for 24 h, significantly reduced neurofilament 200 losses to 17% and 3% relative to naive neurofilament 200 protein levels in the ipsilateral and contralateral cortices, respectively. Calpain inhibitor administration abolished neurofilament 68 loss in the ipsilateral cortex and was accompanied by a reduction of putative calpain-mediated neurofilament 68 breakdown products. Spectrin breakdown products mediated by calpain 1 activation were detectable in both hemispheres 24 h after traumatic brain injury and were substantially reduced in animals treated with calpain inhibitor 2 both ipsilaterally and contralaterally to the site of injury. Qualitative immunofluorescence studies of neurofilament 200 and neurofilament 68 confirmed western blot data, demonstrating morphological protection of neuronal structure throughout cortical regions of the traumatically injured brain. Morphological protection included preservation of dendritic structure and reduction of axonal retraction balls. In addition, histopathological studies employing hematoxylin and eosin staining indicated reduced extent of contusion at the injury site. These data indicate that calpain inhibitors could represent a viable strategy for preserving the cytoskeletal structure of injured neurons after experimental traumatic brain injury in vivo.

Similar Articles

Antisaccades and remembered saccades in mild traumatic brain injury

Author(s): Crevits L, Hanse MC, Tummers P, Van Maele G

Subacute to chronic mild traumatic brain injury

Author(s): Mott TF, McConnon ML, Rieger BP

Meta-analysis of APOE4 allele and outcome after traumatic brain injury

Author(s): Zhou W, Xu D, Peng X, Zhang Q, Jia J, et al.

Traumatic brain injuries evaluated in U

Author(s): Jager TE, Weiss HB, Coben JH, Pepe PE

A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury

Author(s): Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, et al.

The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury

Author(s): Büki A, Siman R, Trojanowski JQ, Povlishock JT

Neuronal cytoskeletal changes are an early consequence of repetitive head injury

Author(s): Geddes JF, Vowles GH, Nicoll JA, Révész T

mu-calpain activation and calpain-mediated cytoskeletal proteolysis following traumatic brain injury

Author(s): Kampfl A, Posmantur R, Nixon R, Grynspan F, Zhao X, et al.

Nimodipine attenuates lipid peroxidation during the acute phase of head trauma in rats

Author(s): Ercan M, Inci S, Kilinc K, Palaoglu S, Aypar U