title: Cerebral ischemia and neurogenesis: a two-time comparison.
abstract: BACKGROUND
  This study compares the effect of mild and severe cerebral ischemia on neuronal damage and neurogenesis.
  
  
  METHODS
  Sixteen Sprague-Dawley rats, anesthetized with 0.8 vol% halothane in O(2)/air, were subjected to forebrain ischemia by bilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure = 40 mmHg) for 8 (mild) or 13 (severe) min. Four non-ischemic animals were investigated as naïve controls. Bromodeoxyuridine (50 mg/kg), a marker of new cells, was administrated for seven consecutive postischemic days. After 28 days, animals were perfused with 4% paraformaldehyde and the brains were sliced. Histopathological damage of the hippocampus and the volume of the dentate gyrus were assessed by HE-staining. With immunohistochemistry BrdU-positve cells were detected in the dentate gyrus. The amount of new generated neurons was identified by double-immunofluorescence-staining of BrdU and neuronal marker (NeuN).
  
  
  RESULTS
  In the CA-1 region of the hippocampus, mild ischemia induced damage up to 10% (HE-index 0.8 +/- 1.2) and severe ischemia up to 50% (HE-index 2.1 +/- 1.4). There was no histopathological damage in naïve control animals. The amount of new neurons was increased by 250% after mild insult and by 160% after severe insult compared to the naïve control animals.
  
  
  CONCLUSIONS
  These data indicate that histopathological damage depends on the severity of the ischemic insult and that forebrain ischemia activates generation of new neurons. A mild ischemic challenge appears to be a more potent neurogenic stimulus than severe ischemia. The new neurons survive at least 28 days. This may relate to delayed histopathological and functional recovery after cerebral ischemia.
authors.affiliation: Klinik für Anästhesiologie, Johannes Gutenberg-Universität Mainz, Langenbeckstrasse. 1, 55131, Mainz, Germany. stegema@uni-mainz.de
authors.forename: Uta
authors.initials: U
authors.lastname: Winkelheide
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelhard
authors.forename: Birgit
authors.initials: B
authors.lastname: Kaeppel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
authors.forename: Peter
authors.initials: P
authors.lastname: Hutzler
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kochs
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D018891:Dentate Gyrus; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001786:Blood Glucose