S100B promotes microglia M1 polarization and migration to aggravate cerebral ischemia

Area of Science:

• Neuroscience
• Immunology
• Molecular Biology

Background:

• Microglia play a crucial role in the brain's response to injury, with distinct M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes.
• S100B protein is highly expressed in microglia during cerebral ischemia, but its specific functions in this context are not fully understood.

Purpose of the Study:

• To investigate the role of S100B in microglia polarization and migration during cerebral ischemia.
• To elucidate the underlying molecular mechanisms, including the involvement of NF-κB.
• To evaluate the in vivo effects of S100B in a mouse model of cerebral ischemia.

Main Methods:

• Real-time PCR was used to analyze S100B, M1, and M2 marker expression in a mouse middle cerebral artery occlusion (MCAO) model.
• Migration assays and mechanistic studies explored the role of NF-κB in S100B-mediated effects.
• S100B treatment was administered to MCAO models to assess in vivo outcomes.

Main Results:

• S100B expression correlated with M1 markers and was induced by M1 stimuli while inhibited by M2 stimuli, identifying it as an M1 marker.
• S100B promoted M1 polarization and migration of microglia while inhibiting M2 polarization.
• NF-κB was found to be essential for S100B's control over microglia polarization and migration.
• In vivo, S100B aggravated cerebral ischemia, exacerbating M1 microglia polarization and migration.

Conclusions:

• S100B promotes microglia M1 polarization, which exacerbates cerebral ischemia.
• These findings enhance understanding of S100B's therapeutic potential and that of its antagonists or neutralizing antibodies in stroke treatment.