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 Dowden, J. Articles by Phillis, J. W. Search for Related Content PubMed PubMed Citation Articles by Dowden, J. Articles by Phillis, J. W.

(Stroke. 1999;30:1240-1246.)
© 1999 American Heart Association, Inc.

Original Contributions

Ischemic Preconditioning in 18- to 20-Month-Old Gerbils

Long-Term Survival With Functional Outcome Measures

Jennifer Dowden, BSc Dale Corbett, PhD

From the Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.

Correspondence to Dale Corbett, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's NF, Canada, A1B 3V6. E-mail corbett{at}morgan.ucs.mun.ca

Background and Purpose—In young animals, ischemic preconditioning protects CA1 hippocampal neurons against global ischemia. However, cerebral ischemia occurs most frequently in individuals aged 65 years. This study examined the protection provided by ischemic preconditioning in a population of aged (18- to 20-month-old) gerbils.

Methods—One group of animals was exposed to two 1.5-minute episodes of global ischemia separated by 24 hours and followed 72 hours later by a 5-minute occlusion of both carotid arteries. A second group was given 2 episodes of preconditioning only. Two other groups were exposed to 5 minutes of ischemia or sham surgery. The animals survived 10, 30, or 60 days. Functional and histological assessments were used to determine the extent of protection.

Results—Ten days after ischemia there was >80% protection of CA1 neurons in ischemic preconditioned animals compared with 6% in ischemic gerbils. Nevertheless, these preconditioned animals were impaired in open-field tests of habituation. In addition, CA1 dendritic field potentials were smaller in amplitude compared with those in sham animals. While there was a complete loss of staining for CA1 microtubule-associated protein-2 in ischemic animals, staining in ischemic preconditioned animals was normal. This suggests that dendritic abnormalities per se were not responsible for the observed functional deficits. CA1 cell survival declined to 75% of sham values (P<0.05) at 60 days after ischemia.

Conclusions—Ischemic preconditioning provided substantial neuroprotection in aged gerbils. Nonetheless, the striking dissociation between histological and functional protection provided by ischemic preconditioning in aged animals emphasizes the need to use functional end points and long-term survival when assessing neuroprotection. Although functional recovery was evident with increasing survival time, CA1 cell death continued, thereby raising the possibility that the level of neuroprotection attained was not permanent.

Editorial Comment

Long-Term Survival With Functional Outcome Measures

John W. Phillis, PhD, DSc, Guest Editor

Department of Physiology, Wayne State University, Detroit, Michigan

This article has been cited by other articles:

				D Papadimitriou, T Xanthos, I Dontas, P Lelovas, and D Perrea The use of mice and rats as animal models for cardiopulmonary resuscitation research Lab Anim, July 1, 2008; 42(3): 265 - 276. [Abstract] [Full Text] [PDF]

				N. J. Alkayed, T. Goyagi, H.-D. Joh, J. Klaus, D. R. Harder, R. J. Traystman, and P. D. Hurn Neuroprotection and P450 2C11 Upregulation After Experimental Transient Ischemic Attack Stroke, June 1, 2002; 33(6): 1677 - 1684. [Abstract] [Full Text] [PDF]