Ischemic cell death: Dynamics of delayed secondary energy failure during reperfusion following focal ischemia

W. David Lust, Christopher Taylor, Svetlana Pundik, Warren R. Selman, Robert A. Ratcheson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Reperfusion injury is believed to contribute to the pathophysiology of ischemic cell death, but the precipitating factors have yet to be completely elucidated. The goal of this study was to examine if reflow-induced secondary energy failure is a component in the events that lead to cell death following increasing periods of middle cerebral artery (MCA) occlusion in Wistar rats. Discrete sections within the MCA distribution were dissected and analyzed for high-energy phosphates and glucose. Regional cerebral blood flow was determined by [14C]-iodoantipyrine technique in representative groups. The levels of ATP + P-creatine were initially depressed at the end of the focal ischemia and the concentrations in the penumbra were unchanged for up to 8 h after 2 h of ischemia which contrasts with response in the ischemic core, striatum, and penumbra where the HEP generally recovered to values near those of control only to decrease with increasing periods of reflow. The possibility of a rebound ischemia in secondary energy failure (SEF) was precluded by regional CBF values and concentrations of glucose that were significantly higher than the threshold for an ischemic effect. The depletion of cellular energy stores following SEF strongly indicates that the evolution of infarct during reflow results from loss of ATP and its synthesis.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalMetabolic Brain Disease
Volume17
Issue number2
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Keywords

  • Cerebral blood flow
  • Reperfusion injury
  • Reversible focal ischemia
  • Secondary energy failure

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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