This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheng, H. Articles by Iadecola, C. Search for Related Content PubMed PubMed Citation Articles by Sheng, H. Articles by Iadecola, C. Related Collections Animal models of human disease Embolic stroke Lipid and lipoprotein metabolism

(Stroke. 1999;30:1118-1124.)
© 1999 American Heart Association, Inc.

Original Contributions

Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse

Huaxin Sheng, MD; Daniel T. Laskowitz, MD; G. Burkhard Mackensen, MD; Masaya Kudo, MD; Robert D. Pearlstein, PhD David S. Warner, MD

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

Costantino Iadecola, MD, Guest Editor

Laboratory of Cerebrovascular Biology and Stroke, Department of Neurology, University of Minnesota, Minneapolis, Minnesota

This article has been cited by other articles:

				H. Hayashi, R. B. Campenot, D. E. Vance, and J. E. Vance Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1 J. Neurosci., February 21, 2007; 27(8): 1933 - 1941. [Abstract] [Full Text] [PDF]

				M. Rotstein, H. Bassan, N. Kariv, Z. Speiser, S. Harel, and I. Gozes NAP Enhances Neurodevelopment of Newborn Apolipoprotein E-Deficient Mice Subjected to Hypoxia J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 332 - 339. [Abstract] [Full Text] [PDF]

				R. M. Lane and M. R. Farlow Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease J. Lipid Res., May 1, 2005; 46(5): 949 - 968. [Abstract] [Full Text] [PDF]

				J.-i. Ito, Y. Nagayasu, R. Lu, A. Kheirollah, M. Hayashi, and S. Yokoyama Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action J. Lipid Res., April 1, 2005; 46(4): 679 - 686. [Abstract] [Full Text] [PDF]

				R. Diaz-Arrastia, Y. Gong, S. Fair, K. D. Scott, M. C. Garcia, M. C. Carlile, M. A. Agostini, and P. C. Van Ness Increased Risk of Late Posttraumatic Seizures Associated With Inheritance of APOE{epsilon}4 Allele Arch Neurol, June 1, 2003; 60(6): 818 - 822. [Abstract] [Full Text] [PDF]

				E. Paradis, S. Clement, P. Julien, and M. R. Ven Murthy Lipoprotein Lipase Affects the Survival and Differentiation of Neural Cells Exposed to Very Low Density Lipoprotein J. Biol. Chem., March 7, 2003; 278(11): 9698 - 9705. [Abstract] [Full Text] [PDF]

				M. Koistinaho, M. I. Kettunen, D. M. Holtzman, R. A. Kauppinen, L. S. Higgins, and J. Koistinaho Expression of Human Apolipoprotein E Downregulates Amyloid Precursor Protein-Induced Ischemic Susceptibility Stroke, July 1, 2002; 33(7): 1905 - 1910. [Abstract] [Full Text] [PDF]

				D. Gallagher-Thompson, R. O'Hara, A. Simmons, H. C. Kraemer, and G. M. Murphy Jr Apolipoprotein E isin4 Allele Affects the Relationship between Stress and Depression in Caregivers of Patients with Alzheimer's Disease J Geriatr Psychiatry Neurol, September 1, 2001; 14(3): 115 - 119. [Abstract] [PDF]

				L. K. Ti, J. P. Mathew, G. B. Mackensen, H. P. Grocott, W. D. White, J. G. Reves, and M. F. Newman Effect of Apolipoprotein E Genotype on Cerebral Autoregulation During Cardiopulmonary Bypass Stroke, July 1, 2001; 32(7): 1514 - 1519. [Abstract] [Full Text] [PDF]

				M. O. McCarron, K. W. Muir, J. A. R. Nicoll, J. Stewart, Y. Currie, K. Brown, and I. Bone Prospective Study of Apolipoprotein E Genotype and Functional Outcome Following Ischemic Stroke Arch Neurol, October 1, 2000; 57(10): 1480 - 1484. [Abstract] [Full Text] [PDF]