Effect of melatonin on endogenous glial derived neurotrophic factor and neuroglobin expressions around the hematome in rats with intracerebral hemorrhage

Objective To observe the dynamic expression levels of endogenous glial derived neurotrophic factor (GDNF) and neuroglobin (NGB) in brain tissues around the hematome and the effect of melatonin intervention on endogenous neuroprotection and recovery of nerve cell after intracerebral hemorrhage (ICH) in rats.Methods One hundred and thirty rats were randomly divided into four groups:normal controlgroup (n=10),sham-operatedgroup (n=40),ICH model group (n=40) and melatonin intervention group (n=40); rats in the later two groups were induced ICH models by Rosenberg methods.Neurological function was evaluated with modified Neurological Severity Scale (mNSS) 12 h,and 1,2,4 and 7 d after ICH.The expressions of GDNF and NGB were detected by imrnunohistochemical method.The dynamic GDNF and NGB mRNA expressions were measured by real time-PCR.GDNF protein expression was determined by Western blotting.Results The mNSS scores in melatonin intervention group were significantly lower than those in the model group 1 d to 7 d after ICH (P＜0.05).Immunohistochemistry assay showed that the GDNF expression in the ICH model group and melatonin intervention group was significantly increased at 12 h and still higher than normal control group 7 d after ICH (P＜0.05).GDNF and NGB expressions in melatonin intervention group were significantly higher than those in model group at different times points after ICH (P＜0.05).The GDNF mRNA expression in melatonin intervention group increased and peaked at 12 h,and GDNF mRNA level in model group increased and peaked 1 d after ICH.NGB mRNA expression in model group peaked 1 d,and increased again on 4-7 d; NGB mRNA level in melatonin intervention group increased and peaked at 12 h,then decreased gradually,and increased significantly again 7 d after ICH.The GDNF protein expression in melatonin intervention group was significantly higher than that in the model group 12 h,4 d and 7 d after ICH (P＜0.05).Conclusion Melatonin can improve neurological deficits in rats with ICH,whose neuroprotective and recovery effects might be by inducing early expression of GDNF and NGB. Key words: Melatonin;  Intracerebral hemorrhage;  Endogenous neuroprotectant;  Glial derived neurotrophic factor;  Neuroglobin