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Abstract

Recent research has indicated that calcium-activated neutral proteases, calpains, are essential mediators of cell death in chronic and acute neurodegenerative disorders. Calpain activation has also been linked to Traumatic Brain Injury (TBI)-induced pathology. Specifically, two isoforms of calpain exist in the brain, calpain-2 and calpain-1, yet the specific roles of each enzyme following TBI are not well understood. Using calpain-1 knockout mice (KO), the current study examined the specific role of calpain-1 in neural degeneration following the controlled cortical impact (CCI) rodent model of TBI. Both Calpain-1 KO and wild type mice received a unilateral CCI over the forelimb sensorimotor cortex. Mice were sacrificed three days post-CCI. Their brains were sliced coronally and stained with Nissl, Fluoro-Jade C, and TUNEL. The results demonstrate that the calpain-1 KO mice exhibit significantly smaller contusions and less degenerating neurons surrounding the CCI. These finding suggests that calpain-1 is a mediator of cell death via apoptosis and the down-regulation of this enzyme following a TBI may be neuroprotection in vivo.

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