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Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Melatonin regulates microglial polarization and protects against ischemic stroke-induced brain injury in mice
Donghai Li1, Tianpeng He2, Yue Zhang1
1Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, PR China.
Abstract:
Ischemic stroke is a leading cause of mortality and morbidity worldwide, with neuroinflammation playing a key role in its pathophysiology. Microglia, the primary immune cells in the brain, undergo rapid activation and phenotypic polarization, which are crucial for regulating neuroinflammatory responses following ischemic stroke. Melatonin is a promising neuroprotective agent that can regulate microglial polarization in central nervous system (CNS) diseases. However, the specific mechanism underlying the neuroprotective effects of melatonin against ischemic stroke-induced brain injury by modulating microglial polarization after ischemic stroke remains poorly understood. To investigate this mechanism, we used the transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model in C57BL/6 mice to induce ischemic stroke and administered intraperitoneal melatonin (20 mg/kg) or an equivalent volume of vehicle daily after reperfusion. Our results demonstrated that melatonin treatment reduced the infarct volume, prevented neuronal loss and apoptosis, and improved neurological deficits after ischemic stroke. Furthermore, melatonin attenuated microglial activation and reactive astrogliosis, while promoting the polarization of microglia toward M2 phenotype via signal transducer and activator of transcription 1/6 (STAT1/6) pathways. Collectively, these findings suggest that melatonin exerts neuroprotective effects against ischemic stroke-induced brain injury by modulating microglial polarization toward M2 phenotype and has the potential as a promising candidate for the treatment of ischemic stroke.
Insights
Melatonin reduces brain damage after ischemic stroke by shifting immune cells toward a healing M2 phenotype. This research highlights melatonin
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Ischemic stroke is a major global health concern, with neuroinflammation significantly contributing to its pathology.
- Microglia, the brain's immune cells, play a critical role in neuroinflammation following ischemic stroke through activation and polarization.
- Melatonin shows potential as a neuroprotective agent, but its precise mechanism in modulating microglial polarization after stroke is unclear.
Purpose of the Study:
- To investigate the neuroprotective mechanisms of melatonin in a mouse model of ischemic stroke.
- To determine if melatonin modulates microglial polarization and its downstream effects on brain injury.
Main Methods:
- Transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model in C57BL/6 mice to induce ischemic stroke.
- Administration of melatonin (20 mg/kg) or vehicle daily after reperfusion.
- Assessment of infarct volume, neuronal loss, apoptosis, neurological deficits, microglial activation, astrogliosis, and M2 polarization via STAT1/6 pathways.
Main Results:
- Melatonin treatment significantly reduced infarct volume, neuronal loss, and apoptosis.
- Melatonin improved neurological deficits and attenuated microglial activation and reactive astrogliosis.
- Melatonin promoted M2 microglial polarization through the signal transducer and activator of transcription 1/6 (STAT1/6) pathways.
Conclusions:
- Melatonin exerts neuroprotective effects against ischemic stroke-induced brain injury.
- These effects are mediated by the modulation of microglial polarization toward the M2 phenotype via STAT1/6 signaling.
- Melatonin represents a potential therapeutic candidate for treating ischemic stroke.
