title: Cerebrolysin reduces amyloid-β deposits, apoptosis and autophagy in the thalamus and improves functional recovery after cortical infarction.
abstract: Focal cerebral infarction causes amyloid-β (Aβ) deposits and secondary thalamic neuronal degeneration. The present study aimed to determine the protective effects of Cerebrolysin on Aβ deposits and secondary neuronal damage in thalamus after cerebral infarction. At 24h after distal middle cerebral artery occlusion (MCAO), Cerebrolysin (5 ml/kg) or saline as control was once daily administered for consecutive 13 days by intraperitoneal injection. Sensory function and secondary thalamic damage were assessed with adhesive-removal test, Nissl staining and immunofluorescence at 14 days after MCAO. Aβ deposits, activity of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), apoptosis and autophagy were determined by TUNEL staining, immunofluorescence and immunoblot. The results showed that Cerebrolysin significantly improved sensory deficit compared to controls (p<0.05). Aβ deposits and BACE1 were obviously reduced by Cerebrolysin, which was accompanied by decreases in neuronal loss and astroglial activation compared to controls (all p < 0.05). Coincidently, Cerebrolysin markedly inhibited cleaved caspase-3, conversion of LC3-II, downregulation of Bcl-2 and upregulation of Bax in the ipsilateral thalamus compared to controls (all p<0.05). These findings suggest that Cerebrolysin reduces Aβ deposits, apoptosis and autophagy in the ipsilateral thalamus, which may be associated with amelioration of secondary thalamic damage and functional recovery after cerebral infarction.
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Shihui
authors: S
authors: Xing
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Jian
authors: J
authors: Zhang
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Chao
authors: C
authors: Dang
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Gang
authors: G
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital, Jinan University, No. 613 Huangpu Avenue West, Guangzhou 510630, China.
authors: Yusheng
authors: Y
authors: Zhang
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Jingjing
authors: J
authors: Li
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Yuhua
authors: Y
authors: Fan
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
authors: Zhong
authors: Z
authors: Pei
authors: Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China. Electronic address: zengjs@pub.guangzhou.gd.cn.
authors: Jinsheng
authors: J
authors: Zeng
mesh_terms: D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D020127:Recovery of Function / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects / Q000473:pathology*
chemical_list: D000596:Amino Acids; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C006952:cerebrolysin; D053829:Amyloid Precursor Protein Secretases; D053148:Caspase 3; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
keywords: Amyloid-β; Apoptosis; Autophagy; Cerebral infarction; Cerebrolysin; Thalamus