The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia

W. Dalton Dietrich, Raul Busto, Marcilia Halley, Isabel Valdes

Research output: Contribution to journalArticlepeer-review

290 Scopus citations


We studied whether small variations in intraischemic brain temperature influence the response of the blood-brain barrier (BBB) to transient forebrain global ischemia. Six animal subgroups included rats whose brain temperature was maintained at 30, 33, 36 or 39°C during 20 minutes (min) of 4-vessel occlusion. Control rats without ischemia had brain temperature maintained between 30 and 39°C for a 20 min period. After a 45 min postischemic recirculation period, rats were injected with the protein tracer, horseradish peroxidase (HRP), and perfusion fixed 5 or 15 min later. Control rats showed no leakage of the tracer protein. Postischemic rats in which brain temperature was controlled at either 30 or 33°C failed to demonstrate consistent BBB alterations. In contrast, foci of cortical HRP extravasation were consistently documented in rats whose intraischemic brain temperature was 36°C. Permeability alterations were more widespread in the 39°C ischemic group and occurred in conical, thalamic, hippocampal and striatal regions. The HRP extravasation frequently involved arterioles surrounded by perivascular spaces. Routes of increased permeability to HRP included endothelial pinocytosis, opening of the interendothelial tight junctions and diffuse leakage through damaged endothelial cells. These results demonstrate that brain temperature is a critical factor in determining whether BBB dysfunction is an acute consequence of a transient cerebral ischemic insult.

Original languageEnglish (US)
Pages (from-to)486-497
Number of pages12
JournalJournal of neuropathology and experimental neurology
Issue number5
StatePublished - Sep 1990


  • Blood-brain barrier
  • Brain
  • Cerebral ischemia
  • Temperature

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)


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