The role of thrombin in intracerebral hemorrhage-induced autophagy

Abstract

Objective Thrombin contributed to intracerebral hemorrhage (ICH) induced brain injury and cell death.Autophagy occurred after ICH.In this study,we are going to investigate the role of thrombin in ICH induced autophagy.Methods Male,adult Sprague-Dawley rats received infusion of autologus blood with or without hirudin (thrombin inhibitor) into the right caudate nucleus,the rats were sacrificed at day 7.Rats received an infusion of rat thrombin or vehicle into the right caudate nucleus and were killed 1,3 or 7 days later.Brains were used for Western blotting,immunohistochemistry and electron microscopy analyses.Results We found that microtubule-associated protein 1 light chain 3 (LC3) Ⅱ/LC3 Ⅰ(1.410 ± 0.080) and Cathepsin D (9.12 ± 0.72) levels in ipsilateral basal ganglia were upregulated after ICH and they were blocked by hirudin treatment (LC3 Ⅱ/LC3 Ⅰ 1.030 ±0.170 and Cathepsin D 6.63 ± 1.22).LC3 Ⅱ/LC3 Ⅰ (0.730 ±0.070),Cathepsin D (10.34 ±2.22) expression were increased in the ipsilateral basal ganglia after thrombin infusion comparing to saline injected (LC3 Ⅱ/LC3 Ⅰ 0.402 ±0.104,Cathepsin D 4.94 ± 1.11),vacuole formation were observed under electron microscopy 3 days after thrombin injected.Conclusion Thrombin plays an important role in ICH induced autophagy. Key words: Intracerebral hemorrhage; Brain injury; Thrombin ; Autophagy