Transient Forebrain Ischemia Protects Against Subsequent Focal Cerebral Ischemia Without Changing Cerebral Perfusion

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Abstract
The possibility that the brain may be preconditioned to be more tolerant of ischemia is an important concept with important clinical implications. Exploring the concept offers the possibility of advancing our understanding of protective molecular responses in the brain. This article compares two preconditioning methods and explores the role that changes in regional cerebral blood flow (rCBF) may play in conferring ischemic protection. Temporary occlusion of the middle cerebral artery (MCA) using the thread model was preceded 4 days earlier by short-lasting focal or global ischemia or by sham surgery. rCBF was measured in the frontoparietal region of the ischemic hemisphere during all focal ischemia episodes. Four days after the second ischemic exposure, animals were killed, and the size of infarction was determined. rCBF was significantly higher in the frontoparietal region during MCA occlusion when it was preceded by prior focal ischemia (36.8 +/- 7.6 mL x 100 g-1 at 30 minutes) compared with controls (24.7 +/- 4.0 mL x 100 g-1.min-1, P = .0008). Despite this, there was no significant difference in the resulting infarct volume. In contrast, when MCA occlusion was preceded by global ischemia, infarct volume was significantly reduced (68.1 +/- 30.9 mm3 in the controls versus 22.9 +/- 22.1 mm3 in the preconditioned group, P = .002) without significant change in rCBF. Protection from ischemic injury requires specific conditions of prior exposure to ischemia. Improved perfusion would not seem to be a sufficient or necessary accompaniment to providing neuroprotection.