Neurocritical Care

, 9:387

Cerebral Ischemia and Neurogenesis: A Two-time Comparison

  • Uta Winkelheide
  • Kristin Engelhard
  • Birgit Kaeppel
  • Jürgen Winkler
  • Peter Hutzler
  • Christian Werner
  • Eberhard Kochs
TRANSLATION RESEARCH

DOI: 10.1007/s12028-008-9121-8

Cite this article as:
Winkelheide, U., Engelhard, K., Kaeppel, B. et al. Neurocrit Care (2008) 9: 387. doi:10.1007/s12028-008-9121-8

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 O2/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.

Keywords

Neurogenesis Dentate gyrus Insult severity Cerebral ischemia 

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Uta Winkelheide
    • 1
  • Kristin Engelhard
    • 1
  • Birgit Kaeppel
    • 2
  • Jürgen Winkler
    • 3
  • Peter Hutzler
    • 4
  • Christian Werner
    • 1
  • Eberhard Kochs
    • 2
  1. 1.Klinik für AnästhesiologieJohannes Gutenberg-Universität MainzMainzGermany
  2. 2.Klinik für AnaesthesiologieKlinikum rechts der IsarMunichGermany
  3. 3.Klinik und Poliklinik für NeurologieUniversität RegensburgRegensburgGermany
  4. 4.National Research Center for Envirnment and HealthInstitut für PathologieMunichGermany

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