(Stroke. 1999;30:1118-1124.)
© 1999 American Heart Association, Inc.
Original Contributions |
Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse
From the Departments of Anesthesiology (H.S., D.S.W.), Medicine (Neurology) (D.T.L.), and Surgery (R.D.P., D.S.W.), Duke University Medical Center, Durham, NC; Department of Anesthesiology, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany (G.B.M.); and the Department of Anesthesiology and Resuscitation, Yamagata University, Yamagata, Japan (M.K.).
Correspondence to David S. Warner, MD, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710. E-mail warne002{at}mc.duke.edu
Background and Purpose—Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult.
Methods—ApoE deficient (n=16) and wild type (n=17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia.
Results—The percentage of dead hippocampal CA1 neurons (mean±SD) was greater in the apoE-deficient group (apoE deficient=67±30%; wild type=37±33%; P=0.011). A similar pattern was observed in the caudoputamen (P=0.002) and neocortex (P=0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia.
Conclusions—ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia.
Editorial Comment
Laboratory of Cerebrovascular Biology and Stroke, Department of Neurology, University of Minnesota, Minneapolis, Minnesota
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