Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury.

Experimental Neurology
Kathleen M SchochKathryn E Saatman

Abstract

Traumatic brain injury (TBI) results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Although the specific inhibitor of calpains, calpastatin, is present within neurons, normal levels of calpastatin are unable to fully prevent the damaging proteolytic activity of calpains after injury. In this study, increased calpastatin expression was achieved using transgenic mice that overexpress the human calpastatin (hCAST) construct under control of a calcium-calmodulin-dependent kinase II α promoter. Naïve hCAST transgenic mice exhibited enhanced neuronal calpastatin expression and significantly reduced protease activity. Acute calpain-mediated spectrin proteolysis in the cortex and hippocampus induced by controlled cortical impact brain injury was significantly attenuated in calpastatin overexpressing mice. Aspects of posttraumatic motor and cognitive behavioral deficits were also lessened in hCAST transgenic mice compared to their wildtype littermates. However, volumetric analyses of neocortical contusion revealed no histological neuroprotection at either acute or long-term time points. Partial hippocampal ...Continue Reading

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Citations

Dec 5, 2012·Brain : a Journal of Neurology·Ann C McKeeRobert C Cantu
Jan 25, 2014·Brain Injury : [BI]·Shuang LiuYangming Qian
Jan 12, 2013·Journal of Neurochemistry·Kathleen M SchochKathryn E Saatman
Feb 24, 2015·Frontiers in Cellular Neuroscience·Vanessa M MachadoInês M Araújo
Sep 7, 2016·Behavioural Brain Research·Eric Peter ThelinBo-Michael Bellander
Jun 15, 2018·Journal of Neurotrauma·Xin Lin TanSandy R Shultz
Jun 14, 2019·Frontiers in Cellular Neuroscience·Cheng-Hsin Liu, Matthew Neil Rasband
Jun 12, 2018·Restorative Neurology and Neuroscience·Diana M SamaKathryn E Saatman
Mar 17, 2018·Neuroscience and Biobehavioral Reviews·Laura B TuckerJoseph T McCabe

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