Profilin 1 knockdown prevents ischemic brain damage by promoting M2 microglial polarization associated with the...

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglial polarization towards the anti-inflammatory M2 phenotype is crucial for resolving neuroinflammation and stroke intervention.
• The actin cytoskeleton, regulated by proteins like Profilin 1 (PFN1), is vital for microglial functions such as migration and phagocytosis.
• The specific role of PFN1 in microglial polarization and its impact on ischemia/reperfusion injury remain largely unexplored.

Purpose of the Study:

• To investigate the role of Profilin 1 (PFN1) in microglial polarization.
• To determine the effect of PFN1 modulation on experimental stroke models.
• To elucidate the therapeutic potential of targeting PFN1 in neuroinflammation and stroke.

Main Methods:

• In vitro studies using BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGDR).
• In vivo studies involving male mice undergoing transient middle cerebral artery occlusion (MCAO) to induce stroke.
• Assessment of microglial polarization (M1/M2 phenotypes), RhoA/ROCK pathway activation, brain infarct volume, edema, cerebral blood flow, and neurological deficits.

Main Results:

• Knockdown of PFN1 inhibited M1 microglial polarization and promoted M2 polarization in BV2 cells post-OGDR and in mice post-MCAO.
• The RhoA/ROCK pathway was identified as a regulator of PFN1 in microglial polarization.
• PFN1 knockdown significantly reduced brain infarcts and edema, improved cerebral blood flow, and ameliorated neurological deficits in MCAO-injured mice.

Conclusions:

• Profilin 1 (PFN1) plays a significant role in regulating microglial polarization during ischemia/reperfusion injury.
• Inhibition of PFN1 promotes a shift towards the neuroprotective M2 microglial phenotype.
• Targeting PFN1 demonstrates therapeutic potential for mitigating brain damage and improving outcomes in stroke.