title: Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy.
abstract: Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, we investigated whether GM1 can protect against ischemic brain injury and whether it targets the autophagy pathway. GM1 was delivered to Sprague-Dawley male rats at 3 doses (25 mg/kg, 50 mg/kg, 100 mg/kg) by intraperitoneal injection soon after reperfusion and then once daily for 2 days. The same volume of saline was given as a control. Tat-Beclin-1, a specific autophagy inducer, was administered by intraperitoneal injection at 24 and 48 hours post-MCAO. Infarction volume, mortality and neurological function were assessed at 72 hours after ischemic insult. Immunofluorescence and Western blotting were performed to determine the expression of autophagy-related proteins P62, LC3 and Beclin-1 in the penumbra area. No significant changes in mortality and physiological variables (heart rate, blood glucose levels and arterial blood gases) were observed between the different groups. However, MCAO resulted in enhanced conversion of LC3-I into LC3-II, P62 degradation, high levels of Beclin-1, a large area infarction (26.3±3.6%) and serious neurobehavioral deficits. GM1 (50 mg/kg) treatment significantly reduced the autophagy activation, neurobehavioral dysfunctions, and infarction volume (from 26.3% to 19.5%) without causing significant adverse side effects. However, this biological function could be abolished by Tat-Beclin-1.
  
  
  CONCLUSIONS
  GM1 demonstrated safe and robust neuroprotective effects that are associated with the inhibition of autophagy following experimental stroke.
authors.affiliation: Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anatomy, Heze Medical College, Shandong, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Tian
authors.affiliation: Osteopathic Medicine, Des Moines University, Des Moines, Iowa, United States of America.
authors.forename: Mitchell King-Wei
authors.initials: MK
authors.lastname: Long
authors.affiliation: Department of Neurology, People's hospital of Deyang City, Sichuan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anatomy & Histology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Anatomy & Histology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Changman
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D005677:G(M1) Ganglioside; D015696:Gene Products, tat; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D000071456:Sequestosome-1 Protein; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C491079:Sqstm1 protein, rat