title: Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats.
abstract: 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.
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Xialin
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Jizi
authors.initials: J
authors.lastname: Jin
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Lixuan
authors.initials: L
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Xinyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Weiwen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH).
authors.forename: Kunqin
authors.initials: K
authors.lastname: Lin
authors.affiliation: Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (XZ, QH, JJ, LZ, XL, WS, KL, EX); and Department of Neurology, Provincial People's Hospital, Guangdong No.2, Guangzhou, China (QH). enxu@163.net.
authors.forename: En
authors.initials: E
authors.lastname: Xu
mesh_terms: D000367:Age Factors; D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: C400541:CA 074 methyl ester; D004151:Dipeptides; D002401:Cathepsin B
keywords: CA-074Me; Cathepsin B; Cerebral infarction; Gliosis; Protease; Secondary degeneration; Stroke; Thalamus.