L-deprenyl reduces brain damage in rats exposed to transient hypoxia-ischemia

Author(s): Aukema, W., Hom, H., Korf, J., Terhorst, G. J.

Journal/Book: Stroke. 1995; 26: 7272 Greenville Avenue, Dallas, TX 75231-4596. Amer Heart Assoc. 1883-1887.

Abstract: 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.

Note: Article S Knollema, Univ Groningen, Ctr Behav Cognit & Neurosci, Dept Biol Psychiat, POB 30001, 9700 Rb Groningen, Netherlands

Keyword(s): cerebral ischemia, transient; free radicals; monoamine oxidase inhibitors; superoxide dismutase; rats; CUZN-SUPEROXIDE-DISMUTASE; PARKINSONS-DISEASE; TRANSGENIC MICE; (-)DEPRENYL; INJURY; NEUROTOXICITY; REPERFUSION; MECHANISMS; LIFE

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