The Journal of neuroscience : the official journal of the Society for Neuroscience
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In the gerbil, brief global forebrain ischemia induces profound habituation and working memory impairments that stem from delayed hippocampal CA1 death. Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to investigate whether prolonged postischemic hypothermia provided long-term CA1 and functional neuroprotection. ⋯ Similar trends were found at more caudal CA1 levels. These results clearly show that postischemic hypothermia provides effective and long-lasting neuroprotection, which depends upon the delay to initiation, duration, and degree of cooling and survival time. The protracted functional and histological benefit observed justifies further basic and clinical investigation.
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Comparative Study
Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures.
In vitro ischemia models have utilized oxygen, or oxygen and glucose deprivation to simulate ischemic neuronal injury. Combined oxygen and glucose deprivation can induce neuronal damage which is in part mediated through NMDA receptors. Severe oxygen deprivation alone however can cause neuronal injury which is not NMDA mediated. ⋯ Raising the pH using Hepes buffer during complete oxygen deprivation did not result in neuronal protection by NMDA receptor blockade. Partial oxygen deprivation alone, partial oxygen deprivation combined with glucose deprivation, glucose deprivation alone, and also glutamate exposure, all produced neuronal damage that was reduced by NMDA receptor blockade. The presence of glucose during complete oxygen deprivation appears to prevent glutamate receptor blockade from reducing neuronal injury in organotypic hippocampal cultures.
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Hindpaw injection of formalin produces acute (Phase 1) and persistent (Phase 2) nociceptive behaviors. This model has provided critical evidence supporting a contribution of central sensitization (hyperexcitability of spinal neurons) to the expression of persistent pain. Here, we evaluated the contribution of ongoing peripheral nerve inputs to Phase 2 pain responses. ⋯ After Phase 1 subsided, but before Phase 2 began, we locally anesthetized the ipsilateral or contralateral (control) hindpaw with a hydrophilic lidocaine derivative, QX-314 (2%). Intraplantar QX-314 blocked Phase 2 pressor, tachycardia and behavioral responses only when injected into the paw that received formalin (2.5% or 10.0%). We conclude that persistent ongoing activity in peripheral afferent fibers during Phase 2 is required for the persistent pain evoked by formalin.
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Classical fear conditioning was used in the present study as a model for investigating emotional learning and memory in human subjects with lesions to the medial temporal lobe. Animal studies have revealed a critical role for medial temporal lobe structures, particularly the amygdala, in simple and complex associative emotional responding. ⋯ This impairment could not be accounted for by deficits in nonassociative sensory or autonomic performance factors, or by differences in declarative memory for the experimental parameters. These results show that temporal lobe structures in humans, as in other mammals, are important components in an emotional memory network.
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Neurotrophic factor expression in the adult mammalian CNS is largely neuronal. However, upon traumatic injury reactive astrocytes express a number of neurotrophic factors including ciliary neurotrophic factor (CNTF), fibroblast growth factor (FGF), and NGF. In this study, we examined whether the upregulation of neurotrophic factors in reactive astrocytes and cultured astrocytes is a consequence of separation from their neuronal counterparts, and whether neurotrophic factor levels can be regulated by placing astrocytes into coculture with neurons. ⋯ In contrast, phosphorylation of TrkB by exogenous BDNF was undetectable by 24 hr and could not be reactivated after this point. These data suggest that the intimate association of astrocytes and neurons in the CNS serves to suppress astrocyte-derived neurotrophic factor expression and that neuronal loss leads to a derepression of neurotrophic factor synthesis in astrocytes. However, the upregulation of endogenous BDNF and CNTF observed after excitotoxic lesion in this culture model are insufficient to activate signal transduction and protect against neuronal loss.