Effects of melatonin on microglia activation in rats with acute intracerebral hemorrhag

Abstract

Objective To investigate the effects of melatonin on activation of microglia and the changes of superoxide dismutase (SOD) and malondialdehyde (MDA) after intracerebral hemorrhage (ICH) in rats. Methods One hundred and thirty male SD rats were randomly divided into four groups: normal group,sham-operated group,intracerebral hemorrhage model group (Model group) and melatonin intervention group (MT group). Each group was further divided into 5 subgroups respectively at 12 h,1 d, 2 d,4 d and 7 d after modeling. The ICH models were made in SD rats by using Rosenberg methods. Melatonin in dose of 10 mg/ kg in solution of 1 mg/ mL was given intraperitoneally to rats of MT group. The morphology of microglia was observed under electron microscope. OX42-positive cells were detected by immunohistochemical (ABC) methods. The contents of MDA or the activity of SOD was measured respectively by thiobarbituric acid or xanthine oxidation method. Results Electron microscope showed that the activation of microglia cell displayed in ameboid shape and swelling of neuron in hemisphere cortex in model group at 2 d after ICH,the activation of microglia cell of the cortex was insignificant in MT group. OX42-positive microglia cell in large amount surrounded the hematoma at 12 h after ICH,peaked at 1 d and lasted for 7 d. OX42-positive microglia cells in MT group were significantly fewer than that in model group at different intervals after ICH (P <0.05). The content of MDA in model group increased significantly after ICH,and higher than that in normal group at 7 d,[(0.875 ±0.098) nmol/ mg prot vs. (0.725 ±0.061) nmol/ mg prot,P <0.05,whereas the activity of SOD changes in the opposite direction,(70.46 ±3.12) U/ mg prot vs. (85.86 ±4.95) /U/ mg prot,P <0.05. Compared with model group,the content of MDA were lower and the activity of SOD were higher in MT group after ICH (P <0.05). Conclusion Melatonin provides a protective effect on the damage of nerve cell after ICH. The mechanism might be associated with melatonin by reducing the level of oxidative stress in brain tissue and attenuating the activation of microglia after ICH. Key words: Melatonin; Intracerebral hemorrhage; Microglia; Oxidative stress; Superoxide dismutase; Rats