title: Endothelin receptors A and B are expressed in distinct cellular compartments of rat hippocampus following global ischemia: an immunocytochemical study.
abstract: OBJECTIVE
  The syntheses of endothelin receptors A and B were previously shown to be upregulated in rat dorsal hippocampus after traumatic brain injury. Here we characterize endothelin receptor A and endothelin receptor B cellular distribution in hippocampus after permanent global brain ischemia and their possible association to nerve cell injury.
  
  
  METHODS
  Twenty-minute global ischemia was induced using the Pulsinelli's four-vessel occlusion in conjunction with systemic hypovolemia in male rats. Endothelin receptor A and endothelin receptor B immunoreactivities from sham-operated and ischemic rats were assessed qualitatively in dentate gyrus, Cornu Ammonis, and hilus regions of the hippocampus. Quantitative immunoreactivity measurements were also obtained by optical densitometry.
  
  
  RESULTS
  In sham-operated control hippocampus, endothelin receptor A immunoreactivity was absent in nerve cell bodies but strongly expressed in the mossy fiber pathway (axons of dentate gyrus granule cells). After ischemia endothelin receptor A immunoreactivity in the same regions was reduced by 40-50% from control. In contrast, endothelin receptor B immunoreactivity in control hippocampus was widely distributed in pyramidal neurons, granule cells and glial cells, this immunoreactivity increasing by approximately 25-30% after ischemia.
  
  
  CONCLUSIONS
  Endothelin receptor A's marked decrease in mossy fibers after ischemia may contribute to glutamate release from mossy fiber terminals, thus enhancing excitotoxic effects on their Cornu Ammonis synaptic targets. Additionally, endothelin receptor B increased expression in neurons and glia could be related to a more generalized activation of survival mechanisms involving elements of the neurovascular unit.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Kreipke
authors.forename: Christian A
authors.initials: CA
authors.lastname: Reynolds
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Schafer
authors.forename: Steven
authors.initials: S
authors.lastname: Schafer
authors.forename: Ryan
authors.initials: R
authors.lastname: Pirooz
authors.forename: José A
authors.initials: JA
authors.lastname: Rafols
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D002451:Cell Compartmentation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000098:blood supply / Q000737:chemistry* / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000737:chemistry* / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D018698:Glutamic Acid