L-DEPRENYL REDUCES BRAIN-DAMAGE IN RATS EXPOSED TO TRANSIENT HYPOXIA-ISCHEMIA

Background and Purpose L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine a nd 6-hydroxydopamine. Experiments were conducted to test whether L-dep renyl prevents or reduces cerebral damage in a transient hypoxia/ische mia 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/ische mia period was induced by simultaneous occlusion of the left common ca rotid artery and reduction of the percentage of oxygen in the gas mixt ure 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-de prenyl 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, respec tively) 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 hip pocampus and the cortex. Conclusions The results show that L-deprenyl is effective as a prophylactic treatment for brain tissue when it is a dministered before hypoxia/ischemia. Mechanisms responsible for the ob served protection remain unclear. The regional differences in damage, however, are in accordance with the reported regional increase in supe roxide dismutase and catalase activities after L-deprenyl treatment, s uggesting the involvement of free radicals and scavenger enzymes.