Melatonin attenuates microglial activation and improves neurological functions in rat model of collagenase-induced intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a severe form of stroke with a high mortality rate. It is also an important cause of permanent disability. Apart from hematoma growth and edema development, inflammatory responses and oxidative stress are responsible for poor outcomes after ICH. Due to its antioxidant, anti-inflammatory and anti-apoptotic properties, melatonin is a neuroprotective molecule against different neurological diseases. The protective roles of melatonin on ICH, particularly in the collagenase-induced ICH model, have not been well studied. The present study aims to explore neuroprotective effects of melatonin against ICH. At 24 hours after ICH induction, rats exhibited neurological deficits with mild loss in body weight (BW). Hematoma was found in the brain parenchyma with ED-1+ activated microglia and TUNEL+ apoptotic cells in the perihematomal region. As an in vitro model of ICH, SH-SY5Y cells were treated with red blood cell lysate. This treatment significantly reduced cell viability; however, melatonin (10-5 M) restored the cell viability. At 72 hours after ICH, rats treated with melatonin (50 mg/kg) at 2, 24 and 48 hours had reduced perihematomal microglial activation. However, there was no effect on hematoma size or perihematomal apoptosis. We further treated rats with 50 mg/kg melatonin starting at 2 hours and repeating at 24-hour intervals for two or seven more days. Both melatonin treatments improved post-ICH neurological functions, and the effect was most pronounced at 4 days after ICH. Since studies regarding the protective roles of melatonin on ICH remain very limited, our study advances our understanding of the potential use of melatonin as a treatment for ICH.

Melatonin mitigates type 1 diabetes‐aggravated cerebral ischemia‐reperfusion injury through anti‐inflammatory and anti‐apoptotic effects

“…Melatonin dose between 5 and 15 mg/kg protects against focal cerebral ischemia (Pei et al., 2002 ). Evaluation of melatonin at doses of 20 or 50 mg/kg in a rat model of intracerebral hemorrhage has failed to find any beneficial effect on hematoma size and apoptosis at 72 h (Leung & Cheung, 2021 ). In the planning of the present study, melatonin doses of 5 and 10 mg/kg were used.…”