The Posthemorrhagic Neuroprotective Effects of Minocycline by Inducing M2 Microglia Polarization in ICH

Intracerebral hemorrhage (ICH) is the deadliest and lethal subtype of stroke which accounts for 15-20% of all strokes. ICH is appraised to influence over a million people worldwide each year which is expected to rise substantially as the population ages. Despite the many studies that have been done, there is no authentic treatment for ICH. Therefore, the incessant research for new methods of treating ICH continues, with the hope of ameliorating both the quality and profitability of therapies. Microglial polarization is an innate immune response to ICH. Microglia can be polarized and developed classic M1 (proinflammatory) or M2 (anti-inflammatory) phenotypes by blood components. The M1 phenotype can produce factors that lead to neuroinflammation (which is a major contributor to ICH progression), iron accumulation, and reactive oxygen species (ROS) production that exacerbate brain injury and finally cause brain damage. The M2 microglia can produceanti-inflammatory factors (IL-10, transforming growth factor beta (TGFβ)) and promote hematoma clearance through phagocytosis and promotion of angiogenesis. The variant impacts of microglial polarization in ICH recommend that restraint of M1 microglial activation inthe early phase of ICH and promotion of a shift from M1 to M2 phenotype in the late stage could be a challenging therapeutic target for ICH treatment.Current evidence recommends that the antibiotic minocycline (a tetracycline derivative) could be a potential therapeuticdrug for neuroinflammatory disease treatment owing to its anti-neuroinflammatory effects. Minocycline is capable of crossing the blood brain barrier which limits inflammation by reducing M1 microglia marker protein (CD68, CD16) expression and inducing M2 microglialpolarization via upregulation of the TrkB/BDNF pathway. Conclusion: Therefore, anti-inflammatory agents such as minoycline which are involved in microglial polarization process are welcomed in the continuing struggle against inflammatory disease.