Time-dependent changes in CRH concentrations and release in discrete brain regions following global ischemia: effects of MK-801 pretreatment
Abstract
The excitatory actions of corticotropin-releasing hormone (CRH) in the brain and the neuroprotective effects of CRH antagonists in models of ischemia suggest a role for this peptide in the cascade of events leading to cellular damage. The present study aimed to characterize endogenous activation of CRH in discrete brain regions following global ischemia. Time-dependent changes in CRH concentrations were assessed in 10 brain regions including hippocampal, parahippocampal, and hypothalamic regions as well as the amygdala and the frontal cortex at three post-ischemic intervals: 4, 24, and 72 h (Experiment 1). The impact of pretreatment with a neuroprotective dose of the NMDA antagonist (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801; hydrogen maleate) on 24-h ischemia-induced CRH concentrations in the 10 brain regions was also determined (Experiment 2). In vivo microdialysis was used to assess dynamic fluctuations in CRH release at the dorsal hippocampus (CA1 pyramidal layer) and central nucleus of the amygdala (CeA; Experiment 3). Our findings revealed a rapid elevation of CRH concentrations at the piriform cortex (Pir) and hypothalamic nuclei following global ischemia. This was ...Continue Reading
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