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(Stroke. 1997;28:428-432.)
© 1997 American Heart Association, Inc.

Articles

Protection With Lubeluzole Against Delayed Ischemic Brain Damage in Rats

A Quantitative Histopathologic Study

Marc Haseldonckx; Jos Van Reempts; Mies Van de Ven; Luc Wouters Marcel Borgers, PhD

the Department of Morphology, Life Sciences, Janssen Research Foundation, Beerse, Belgium.

Correspondence to J. Van Reempts, Department of Morphology, Life Sciences, Janssen Research Foundation, B-2340, Beerse, Belgium. E-mail jvreempt@janbe.jnj.com.

Background and Purpose Cerebral ischemia may lead to glutamate-induced excitotoxic damage in vulnerable brain areas. Lubeluzole is not an N-methyl-D-aspartate antagonist but prevents postischemic increase in extracellular glutamate concentrations. The present study examined whether lubeluzole, administered after global incomplete ischemia in rats, is capable of preserving the structural integrity of CA1 hippocampus.

Methods Ischemia was induced by bilateral carotid artery occlusion and severe hypotension for a duration of 9 minutes. Delayed neuronal cell death was histologically evaluated 7 days later. This was done by scoring acidophilic cell change and coagulative necrosis and by counting the number of surviving neurons in the CA1 subfield. Experiments were performed according to a paired design (13 animals per treatment group).

Results Posttreatment with lubeluzole (0.31 mg/kg IV bolus at 5 minutes and 0.31 mg/kg IV infusion during 1 hour) resulted in significant neuroprotection. Whereas in the untreated rats there were 42 (median) viable neurons per millimeter CA1 layer in the left and 69 in the right hemisphere, in the drug-treated rats 99 viable neurons per millimeter were found in the left (P=.002) and 113 in the right hemisphere (P=.013). Histological scores, reflecting altered staining properties of the hippocampal cells, correlated strongly with the quantitative data, reflecting the structural integrity of CA1 pyramidal neurons.

Conclusions Lubeluzole, when administered after an ischemic insult in rats, protects vulnerable brain regions against delayed structural injury. The results support the potential clinical use of this new drug in stroke treatment.

Editorial Comment

A Quantitative Histopathologic Study

James A. Clemens, PhD, Guest Editor

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind

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