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(Stroke. 1998;29:2616-2621.)
© 1998 American Heart Association, Inc.

Original Contributions

Amelioration of Hippocampal Neuronal Damage After Global Ischemia by Neuronal Overexpression of BCL-2 in Transgenic Mice

Kazuo Kitagawa, MD; Masayasu Matsumoto, MD; Yoshihide Tsujimoto, PhD; Toshiho Ohtsuki, MD; Keisuke Kuwabara, MD; Kohji Matsushita, MD; Gongming Yang, MD; Hiroki Tanabe, PhD; Jean-Claude Martinou, PhD; Masatsugu Hori, MD Takehiko Yanagihara, MD

From the Division of Strokology, First Department of Internal Medicine (K.K., M.M., T.O., K.K., K.M., G.Y., M.H.), Department of Neurology (M.M., T.Y.), and Department of Molecular Genetics, Biomedical Research Center (Y.T., H.T.), Osaka University Medical School, Osaka, Japan; and Geneva Biomedical Research Institute, Geneva, Switzerland (J-C.M.).

Background and Purpose—Reports suggesting the involvement of apoptosis in ischemic neuronal damage have been accumulating, and protection against apoptotic death by BCL-2 has been shown in many types of cells. Overexpression of BCL-2 has been shown to reduce infarct size after focal ischemia. The purpose of the present study was to assess whether BCL-2 exerted its effect on selective neuronal vulnerability after transient global ischemia.

Methods—Transgenic mice overexpressing BCL-2 in neurons and their littermates were subjected to transient forebrain ischemia for 12 minutes, and the hippocampus was examined 7 days later with conventional histology, immunohistochemistry, and in situ terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end-labeling of fragmented DNA.

Results—Although both types of mice showed a similar degree of ischemic insult, transgenic mice showed a lesser degree of neuronal death together with DNA fragmentation in the hippocampus than their littermates.

Conclusions—Overexpression of BCL-2 in neurons mitigates selective neuronal vulnerability in the hippocampus of transgenic mice after transient global ischemia.

Editorial Comment

Pak H. Chan, PhD, Guest Editor

Departments of Neurosurgery and, Neurology & Neurological Sciences, Program in Neurosciences, Stanford University, Palo Alto, California

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