Gong Ye, He Yangdong, Gu Yuxiang, Keep Richard F, Xi Guohua, Hua Ya
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-0532, USA.
Acta Neurochir Suppl. 2011;111:113-7. doi: 10.1007/978-3-7091-0693-8_18.
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.
脑出血（ICH）可导致老年大鼠严重脑损伤。脑出血后大脑会发生自噬，本研究探讨了衰老对脑出血后自噬的影响。18 - 22月龄的老年雄性Fischer大鼠和4 - 6月龄的年轻雄性Fischer大鼠接受脑内注射100 μL自体全血。在第7天处死大鼠进行蛋白质免疫印迹分析，以检测微管相关蛋白轻链3（LC3，自噬体的生物标志物）和组织蛋白酶D（一种溶酶体生物标志物）。在脑出血后11周处死大鼠进行脑组织学检查。还检测了与年龄相关的神经功能缺损变化。蛋白质免疫印迹显示，与年轻大鼠相比，老年大鼠同侧基底神经节中LC3 - I/LC3 - II转化率更高（p<0.05）。老年大鼠血肿周围组织蛋白酶D水平也更高（p<0.05）。脑出血后老年大鼠的神经功能缺损更严重，且功能恢复较慢（p<0.05）。此外，脑出血后11周，老年大鼠同侧基底神经节中铁蛋白和OX - 42阳性细胞比年轻大鼠更多（p<0.05）。年轻和老年大鼠均出现脑萎缩。总之，脑出血在老年大鼠中会导致更严重的自噬和神经功能缺损。
