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(Stroke. 1995;26:1883-1887.)
© 1995 American Heart Association, Inc.

Articles

L-Deprenyl Reduces Brain Damage in Rats Exposed to Transient Hypoxia-Ischemia

Siert Knollema; Walter Aukema; Harold Hom; Jakob Korf, PhD Gert J. Ter Horst, PhD

From the University of Groningen, Department of Biological Psychiatry, Groningen, The Netherlands.

Background and Purpose L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model.

Methods Rats were treated for 14 days with 2 mg/kg and 10 mg/kg L-deprenyl or saline. After surgery a 20-minute hypoxia/ischemia period was induced by simultaneous occlusion of the left common carotid artery and reduction of the percentage of oxygen in the gas mixture to 10%. Rats were killed 24 hours later. Silver staining was used to reveal damage in several brain regions.

Results In the brain, both L-deprenyl dosages reduced damage up to 78% compared with the controls. Total brain damage was decreased from 23%-31% to 5%-9% with the L-deprenyl treatment (2 mg/kg: F_1.13=6.956, P<.05; 10 mg/kg: F_1.13=5.731, P<.05). In the striatum, significant treatment effects were found between both the L-deprenyl groups (2 mg/kg and 10 mg/kg, respectively) and the saline group (F_1.13=14.870, P<.005; and F_1.13=8.937, P=.01; respectively). In the thalamus, significant treatment effects were seen in the 2-mg/kg L-deprenyl group (F_1.13=11.638, P<.005) and the 10-mg/kg group (F_1.13=8.347, P<.05) compared with the control group. No significant damage decrease was seen in the hippocampus and the cortex.

Conclusions The results show that L-deprenyl is effective as a prophylactic treatment for brain tissue when it is administered before hypoxia/ischemia. Mechanisms responsible for the observed protection remain unclear. The regional differences in damage, however, are in accordance with the reported regional increase in superoxide dismutase and catalase activities after L-deprenyl treatment, suggesting the involvement of free radicals and scavenger enzymes.

Key Words: cerebral ischemia, transient • free radicals • monoamine oxidase inhibitors • superoxide dismutase • rats

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