Neurobiology of disease
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Neurobiology of disease · Apr 2006
Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemia.
Enriched environment (EE) has been shown to increase neurogenesis in the adult brain. The aim of this study is to determine the effect of EE and spatial learning on neurogenesis following ischemic stroke. Male adult SD rats were subjected to sham surgery or distal middle cerebral artery occlusion (MCAO). ⋯ Increased neuronal differentiation and neurogenesis in the DG were observed in both sham and MCAO rats following 8 weeks in the EE combined with spatial learning, compared to rats housed in the standard environment. EE/Learning also restored the total number of neuroblasts in the DG after MCAO compared to sham. Furthermore, EE/learning enhanced the density of NeuN positive cells in the ischemic penumbra, though no new neurons were detected in this region.
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Neurobiology of disease · Apr 2006
Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition.
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. ⋯ 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.