Rapid preconditioning protects rats against ischemic neuronal damage after 3 but not 7 days of reperfusion following global cerebral ischemia

Miguel A. Pérez-Pinzón, Guang Ping Xu, W. Dalton Dietrich, Myron Rosenthal, Thomas J. Sick

Research output: Contribution to journalArticle

195 Scopus citations

Abstract

Earlier studies indicated that sublethal ischemic insults separated by many hours may 'precondition' and, thereby, protect tissues from subsequent insults. In Wistar rats, we examined the hypothesis that ischemic preconditioning (IPC) can improve histopathological outcome even if the 'conditioning' and 'test' ischemic insults are separated by only 30 min. Normothermic (36.5-37°C) global cerebral ischemia was produced by bilateral carotid artery ligation after lowering mean systemic blood pressure. The conditioning ischemic insult lasted 2 min and was associated with a time sufficient to provoke 'anoxic depolarization' (AD) (i.e., the abrupt maximal increase in extracellular potassium ion activity). After 30 min of reperfusion, 10-min test ischemia was produced, and histopathology was assessed 3 and 7 days later. After 3 days of reperfusion, neuroprotection was most robust in the left lateral, middle and medial subsections of the hippocampal CA1 subfield and in the cortex, where protection was 91, 76, 70 and 86%, respectively. IPC also protected the right lateral, middle and medial subsections of the hippocampal CA1 region. These data demonstrate that neuroprotection against acute neuronal injury can be achieved by conditioning insults followed by only short (30 min) periods of reperfusion. However, neuroprotection almost disappeared when reperfusion was continued for 7 days. When test ischemia was decreased to 7 min, a clear trend of neuroprotection by IPC was observed. These data suggest that subsequent rescue of neuronal populations could be achieved with better understanding of the neuroprotective mechanisms involved in this rapid IPC model.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number2
DOIs
StatePublished - Feb 1997

Keywords

  • Adenosine
  • Global ischemia
  • Hippocampus
  • Ischemic tolerance

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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