Melatonin alleviates asphyxial cardiac arrest-induced cerebellar Purkinje cell death by attenuation of oxidative stress

• Published in: Experimental neurology 2019-10, Vol.320, p.112983-112983, Article 112983
• Main Authors: Cho, Jeong Hwi, Tae, Hyun-Jin, Kim, In-Shik, Song, Minah, Kim, Hyunjung, Lee, Tae-Kyeong, Kim, Young-Myeong, Ryoo, Sungwoo, Kim, Dae Won, Lee, Choong-Hyun, Hwang, In Koo, Yan, Bing Chun, Kang, Il Jun, Won, Moo-Ho, Lee, Jae-Chul
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant enzymes; Antioxidants - pharmacology; Asphyxia - etiology; Asphyxial cardiac arrest; Autophagy - drug effects; Autophagy-like cell death; Heart Arrest - complications; Heart Arrest - pathology; Male; Melatonin; Melatonin - pharmacology; Melatonin receptor; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Purkinje cells; Purkinje Cells - drug effects; Purkinje Cells - metabolism; Purkinje Cells - pathology; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor, Melatonin, MT2 - metabolism
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2019.112983

Although multiple reports using animal models have confirmed that melatonin appears to promote neuroprotective effects following ischemia/reperfusion-induced brain injury, the relationship between its protective effects and activation of autophagy in Purkinje cells following asphyxial cardiac arrest and cardiopulmonary resuscitation (CA/CPR) remains unclear. Rats used in this study were randomly assigned to 6 groups as follows; vehicle-treated sham operated group, vehicle-treated asphyxial CA/CPR operated group, melatonin-treated sham operated group, melatonin-treated asphyxial CA/CPR operated group, PDOT (a MT2 melatonin receptor antagonist) plus (+) melatonin-treated sham operated group and PDOT+melatonin-treated asphyxial CA/CPR operated group. Melatonin (20 mg/kg, i.p., 4 times before CA and 3 times after CA) treatment significantly improved survival rate and neurological deficit compared with the vehicle-treated asphyxial CA/CPR rats (survival rates ≥40% vs 10%), showing that melatonin treatment exhibited protective effect against asphyxial CA/CPR-induced Purkinje cell death. The protective effect of melatonin against CA/CPR-induced Purkinje cell death paralleled a remarkable attenuation of autophagy-like processes (Beclin-1, Atg7 and LC3), as well as a dramatic reduction in superoxide anion radical (O2·-), intense enhancements of CuZn superoxide dismutase (SOD1) and MnSOD (SOD2) expressions. Furthermore, the protective effect was notably reversed by treatment with PDOT, which is a selective MT2 antagonist. In brief, melatonin conferred neuroprotection against asphyxial CA/CPR-induced Purkinje cell death via inhibiting autophagic activation by reducing expressions of O2·- and increasing expressions of antioxidant enzymes, and suggests that MT2 is involved in neuroprotective effect of melatonin against Purkinje cell death caused by asphyxial CA/CPR. •Melatonin prevents cerebellar Purkinje cell death following asphyxial cardiac arrest.•Melatonin attenuates autophagy-like processes via MT2 receptor.•Melatonin attenuates increase of superoxide anion radical via MT2 receptor.•Melatonin maintains antioxidant enzymes expressions via MT2 receptor.