Propagermanium, a CCR2 inhibitor, attenuates cerebral ischemia/reperfusion injury through inhibiting inflammatory...

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Chemokine receptor 2 (CCR2) recruits immune cells to the brain post-ischemic stroke.
• The protective mechanisms of Propagermanium (PG), a CCR2 inhibitor, against ischemic injury remain unclear.

Purpose of the Study:

• To investigate the protective effects and underlying mechanisms of Propagermanium (PG) in a mouse model of ischemic stroke.
• To determine if PG inhibits pro-inflammatory microglia polarization via STAT1 signaling.

Main Methods:

• In vivo: Middle cerebral artery occlusion (MCAO) model in mice; TTC staining, neurological scoring, brain water content, MRI.
• In vitro: BV2 microglia exposed to oxygen-glucose deprivation (OGD)/reoxygenation, LPS, or IL-4.
• Analysis: Real-time PCR, ELISA, immunofluorescence, Western blot for inflammatory markers and STAT1 phosphorylation.

Main Results:

• PG treatment significantly reduced infarct size, brain edema, and improved neurological function in MCAO mice.
• PG inhibited the release of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-17, IL-23) and downregulated pro-inflammatory markers (iNOS, CD86, CD16) in microglia.
• In vitro, PG inhibited BV2 microglia polarization to a pro-inflammatory phenotype by downregulating STAT1 phosphorylation, without affecting the anti-inflammatory phenotype.

Conclusions:

• Propagermanium (PG) exerts neuroprotective effects against ischemic stroke by inhibiting pro-inflammatory microglia polarization.
• The mechanism involves the downregulation of STAT1 signaling, leading to reduced inflammatory responses.
• PG represents a potential therapeutic agent for ischemic stroke by targeting CCR2-mediated neuroinflammation.