title: Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats.
abstract: Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.
authors: Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department, National Key Discipline, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Xin-ran
authors: XR
authors: Chen
authors: Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department, National Key Discipline, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Song-jie
authors: SJ
authors: Liao
authors: Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department, National Key Discipline, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Lan-xiang
authors: LX
authors: Ye
authors: Department of Neurology, the Second People's Hospital of Guangdong Province, Guangzhou 510000, China.
authors: Qiong
authors: Q
authors: Gong
authors: Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department, National Key Discipline, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Qiao
authors: Q
authors: Ding
authors: Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department, National Key Discipline, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Jin-sheng
authors: JS
authors: Zeng
authors: Department of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department, National Key Discipline, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. Electronic address: yujian21cn@163.com.
authors: Jian
authors: J
authors: Yu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology*; D002452:Cell Count; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D007839:Functional Laterality; D019922:GAP-43 Protein / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000209:etiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D010751:Phosphopyruvate Hydratase; D019765:Chondroitin ABC Lyase
keywords: C-4-S; CNS; CS-GAGs; CSPGs; ChABC; Chondroitin sulfate proteoglycans; Chondroitinase ABC; ECM; FITC; GAP-43; MCA; MCAO; Middle cerebral artery occlusion; Neuroprotection; PBS; RHRSPs; SBP; SYN; Systolic blood pressure; VPN; Ventroposterior thalamic nucleus; central nervous system; chondroitin sulfate glycosaminoglycans; chondroitin-4-sulfate; chondroitinase ABC; extracellular matrix; fluoresceine isothiocyanate; growth-associated protein-43; mNSS; middle cerebral artery; middle cerebral artery occlusion; modified neurologic severity scores; phosphate-buffered saline; stroke-prone renovascular hypertensive rats; synaptophysin; ventroposterior thalamic nucleus