Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats

• Published in: Journal of neuropathology and experimental neurology 2016-09, Vol.75 (9), p.816-826
• Main Authors: Zuo, Xialin, Hou, Qinghua, Jin, Jizi, Zhan, Lixuan, Li, Xinyu, Sun, Weiwen, Lin, Kunqin, Xu, En
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Cathepsin B - antagonists & inhibitors; Cathepsin B - metabolism; Cerebral Infarction - drug therapy; Cerebral Infarction - metabolism; Cerebral Infarction - pathology; Dipeptides - pharmacology; Dipeptides - therapeutic use; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Thalamus - drug effects; Thalamus - metabolism; Thalamus - pathology
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/nlw054

Secondary degeneration in areas beyond ischemic foci can inhibit poststroke recovery. The cysteine protease Cathepsin B (CathB) regulates cell death and intracellular protein catabolism. To investigate the roles of CathB in the development of secondary degeneration in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after focal cerebral infarction, infarct volumes, immunohistochemistry and immunofluorescence, and Western blotting analyses were conducted in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats. We observed marked neuron loss and gliosis in the ipsilateral thalamus after dMCAO, and the expression of CathB and cleaved caspase-3 in the VPN was significantly upregulated; glial cells were the major source of CathB. Although it had no effect on infarct volume, delayed intracerebroventricular treatment with the membrane-permeable CathB inhibitor CA-074Me suppressed the expression of CathB and cleaved caspase-3 in ipsilateral VPN and accordingly alleviated the secondary degeneration. These data indicate that CathB mediates a novel mechanism of secondary degeneration in the VPN of the ipsilateral thalamus after focal cortical infarction and suggest that CathB might be a therapeutic target for the prevention of secondary degeneration in patients after stroke.