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 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.