Potential use of melatonin as a therapy for intracerebral haemorrhage

Abstract

INTRODUCTION: Intracerebral haemorrhage (ICH) is a devastating form of stroke and is characterised by rupture of blood vessels within the brain parenchyma. Patients with ICH may suffer from severe neurological sequels like motor deficits and cognitive impairment. We aimed to study the neurological outcomes of ICH. The potential therapeutic effects of melatonin on ICH were also investigated. METHODS: ICH was induced in the rat by an intrastriatal injection of collagenase type IV. Haematoma size and neurological deficits were studied 24 hours later. To study the beneficial effect of melatonin on ICH, repetitive intraperitoneal injections of melatonin were given to the rats at 2, 24, and 48 hours after ICH; they were sacrificed at 72 hours. In addition, the neuroprotective role of melatonin was further investigated in vitro. RESULTS: At 24 hours after the ICH induction, haematoma was found in the brain parenchyma. The rats also manifested neurological deficits. Repetitive intraperitoneal injections of melatonin at 50 mg/kg achieved significant improvement in the rotarod test at 72 hours after ICH when compared to 24 hours. The expression of ED-1 (a marker of activated microglia) in the peri-hematomal tissue was decreased in 50 mg/kg melatonintreated group when compared to the vehicle-treated group. In the in-vitro study, the SH-SY5Y neuronal cells were challenged with red blood cell lysate, and the cell viability was reduced in a dose-dependent manner. Melatonin at optimal concentrations could increase the neuronal viability. CONCLUSION: Our present results reveal some potential neuroprotective effects of melatonin in a rat model of ICH and may provide a new insight to the future drug development for this devastating disease.