Hypothermic Protection in Rat Focal Ischemia Models

Strain Differences and Relevance to "Reperfusion Injury"

Yubo Ren, Megumi Hashimoto, William A. Pulsinelli, Thaddeus Nowak

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Hypothermic protection was compared in Long-Evans and spontaneously hypertensive rat (SHR) strains using transient focal ischemia, and in Wistar and SHR strains using permanent focal ischemia. Focal ischemia was produced by distal surgical occlusion of the middle cerebral artery and tandem occlusion of the ipsilateral common carotid artery (MCA/CCAO). Moderate hypothermia of 2 hours' duration was produced by systemic cooling to 32 °C, with further cooling of the brain achieved by reducing to 30°C the temperature of the saline drip superfusing the exposed occlusion site. Infarct volume was determined from serial hematoxylin and eosin-stained frozen sections obtained routinely at 24 hours, or in some cases after 3 days' survival. In the SHR, moderate hypothermia was only effective when initiated before recirculation after a 90-minute occlusion period. In contrast, the same intervention was strikingly effective in the Long-Evans rat even when initiated after as long as 30-minute reperfusion after a 3-hour occlusion. This magnitude and duration of cooling was not protective in permanent MCA/CCAO in the SHR, but such transient hypothermia did effectively reduce infarct volume after permanent occlusions in Wistar rats. These results show striking differences in the temporal window for hypothermic protection among rat focal ischemia models. As expected, "reperfusion injury" in the Long-Evans strain is particularly responsive to delayed cooling. The finding that the SHR can be protected by hypothermia initiated immediately before recirculation suggests a rapidly evolving component of injury occurs subsequent to reperfusion in this model as well. Hypothermic protection after permanent occlusion in Wistar rats identifies a transient, temperature-sensitive phase of infarct evolution that is not evident in the unreperfused SHR. These observations confirm that distinct mechanisms can underlie the temporal progression of injury in rat stroke models, and emphasize the critical importance of considering model and strain differences in extrapolating results of hypothermic protection studies in animals to the design of interventions in clinical stroke.

Original languageEnglish (US)
Pages (from-to)42-53
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2004

Fingerprint

Inbred SHR Rats
Reperfusion Injury
Ischemia
Hypothermia
Reperfusion
Wistar Rats
Stroke
Long Evans Rats
Temperature
Middle Cerebral Artery Infarction
Common Carotid Artery
Wounds and Injuries
Frozen Sections
Hematoxylin
Eosine Yellowish-(YS)
Brain

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Hypothermic Protection in Rat Focal Ischemia Models : Strain Differences and Relevance to "Reperfusion Injury". / Ren, Yubo; Hashimoto, Megumi; Pulsinelli, William A.; Nowak, Thaddeus.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 24, No. 1, 01.01.2004, p. 42-53.

Research output: Contribution to journalArticle

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