Effect of the first window of ischemic preconditioning on mitochondrial dysfunction following global cerebral ischemia

Miguel A. Pérez-Pinzón, Abdul Basit, Kunjan R. Dave, Raul Busto, Clemence Veauvy, Isabel Saul, Myron D. Ginsberg, Thomas J. Sick

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Rats may develop sustained tolerance against lethal cerebral ischemia after exposure to a sublethal ischemic insult (ischemic preconditioning (IPC)). Two windows for the induction of tolerance by IPC have been proposed, one that occurs within 1 h following IPC, and the other one that occurs 1-3 days after IPC. An important difference between these two windows is that in contrast to the second window, neuroprotection against lethal ischemia is transient in the first window. We tested the hypothesis that rapid IPC would reduce or prevent ischemia-induced changes in mitochondrial function. IPC and ischemia were produced by bilateral carotid occlusions and systemic hypotension (50 mmHg) for 2 and 10 min, respectively. The non-synaptosomal mitochondria were harvested 30 min following the 10 min 'test' ischemia. Mitochondrial rate of respiration decreased by 10% when the substrates were pyruvate and malate, and 29% when the substrates were ascorbic acid and N,N,N′,N′-tetramethyl-p-phenylenediamine (P < 0:01). The activities of complex I-III decreased in ischemic group by 16, 23 (P < 0:05) and 24%, respectively. IPC was unable to prevent decreases in the rate of respiration and activities of different complexes. These data suggest that rapidly induced IPC is unable to protect the integrity of mitochondrial oxidative phosphorylation following cerebral ischemia, perhaps explaining why IPC only provides transitory protection in the 'first window'.

Original languageEnglish (US)
Pages (from-to)181-189
Number of pages9
JournalMitochondrion
Volume2
Issue number3
DOIs
StatePublished - Dec 2002

Keywords

  • Anoxia
  • Cell death
  • Free radicals
  • Tolerance

ASJC Scopus subject areas

  • Biophysics

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