Role of melatonin for repairing the periventricular white matter damage due to hypoxia-ischemia in the developing brain of rat

Abstract

Objective To investigate the protective effect of melatonin and its possible mechanism for repairing in the immature white matter damage due to brain hypoxia-ischemia(HI). Methods Forty-eight three-day SD rats after birth were randomly divided into 3 groups: sham-operated(SHAM) group, HI group and melatonin treatment(MT) group.Periventricular white matter damage(PWMD) to animal models were estabished according to Rice modeling.MT group was treated with melatonin pre-operatively, immediately postoperation, 1 hour postoperation and 24 hours postoperation via intraperitoneal injection, and the other groups were injected with the same volume of dissolvent.The rats were executed by decollation after 2 days and 14 days.The histological changes in periventricular white matter were observed by HE staining and immunohistochemistry. Results For the 3 groups, the structure in ope-ration side of the white matter in the peripheral ventricles of the brain 2 days postoperation were significant different(P<0.05). The O4 positive cells decreased one by one/greatest in the SHAM group[(75.548±7.333)/hpf] followed by MT group[(59.971±3.635)/hpf], and HI group[(40.511±2.848)/hpf](P<0.05). The expression of Casepase-3 increased in the SHAM group(107.724±10.266), MT group(132.289±8.537), and HI group(202.168±14.367), and the difference was statically significant(P<0.05). Ventricular index was greater in operation side of the white matter in the peripheral ventricles of the 14-day- brain in the SHAM group(0.928±0.063), MT group(1.813±0.110), HI group (2.752±0.201), increasingly, while absorbance value of myelin basic protein decreased one by one in sequence(39.504±1.673, 21.729±1.614, 11.344±1.118). Conclusions MT plays a role in protecting the periventricular white matter via inhibiting the apoptosis of oligodendrocyte progenitor cell, and thus benefits the PWMD. Key words: Oligodendrocyte progenitor cell; Melatonin; Caspase-3; Hypoxia-ischemia brain damage; Periventricular white matter damage