Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition - PubMed (original) (raw)

Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition

Michael N DeRidder et al. Neurobiol Dis. 2006 Apr.

Abstract

Apoptotic or necrotic cell death in the hippocampus is a major factor underlying the cognitive impairments following traumatic brain injury. In this study, we examined if traumatic mechanical injury would produce regional activation of calpain and caspase-3 in the in vitro hippocampus and studied how the mechanically induced activation of NR2A and NR2B containing N-methyl-d-aspartate receptors (NMDARs) affects the activation of these proteases following mechanical injury. Following a 75% stretch, significant levels of activated caspase-3 and calpain-mediated spectrin breakdown products were evident only in cells within the dentate gyrus, and little co-localization of the markers was identified within individual cells. After 100% stretch, only calpain activation was observed, localized to the CA3 subregion 24 h after stretch. At moderate injury levels, both caspase-3 and calpain activation was attenuated by blocking NR2B containing NMDARs prior to stretch or by blocking all NMDARs prior to stretch injury. Treatment with an NR2A selective NMDAR antagonist had little effect on either activated caspase-3 or Ab38 immunoreactivity following moderate injury but resulted in the appearance of activated caspase-3 in the dentate gyrus following severe mechanical stretch. Together, these studies suggest that the injury induced activation of NR2A containing NMDARs functions as a pro-survival signal, while the activation of NR2B containing NMDARs is a competing, anti-survival, signal following mechanical injury to the hippocampus.

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Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition - PubMed (original) (raw)