Effects of aging on autophagy after experimental intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) causes severe brain injury in aged rats. Autophagy occurs in the brain after ICH, and the present study examined the effects of aging on autophagy after ICH. Aged (18-22-month) and young (4-6-month) male Fischer rats received an intracerebral injection of 100-μL autologous whole blood. Rats were killed at day 7 for Western blot analysis to measure microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and cathepsin D, a lysosomal biomarker. Rats were killed at 11 weeks after ICH for brain histology. Age-related changes in neurological deficits were also examined. Western blotting showed that the LC3-I/LC3-II conversion ratio in the ipsilateral basal ganglia was higher in aged compared to young rats (p < 0.05). Perihematomal cathepsin D levels were also higher in aged rats (p < 0.05). Neurological deficits after ICH were more severe in aged rats, and they had a slower recovery of function (p < 0.05). In addition, there were more ferritin and OX-42 positive cells in the ipsilateral basal ganglia in aged than in young rats 11 weeks after ICH (p < 0.05). Brain atrophy was found in both young and aged rats. In conclusion, ICH causes more severe autophagy and neurological deficits in aged rats. © 2011 Springer-Verlag/Wien.