Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the RhoA/ROCK pathway.

BACKGROUND

Microglia can be activated as proinflammatory (M1) phenotypes and anti-inflammatory (M2) phenotypes after stroke. Parthenolide (PTL) has anti-inflammatory and protective effects on neurological diseases, but until now, the exact mechanisms of these processes after stroke have been unclear. The purpose of this study was to determine the effect of PTL on microglial polarization after stroke and its target for inducing microglial polarization.

METHODS

Triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and neurological evaluation were performed in a focal transient cerebral ischemia rat model. The human microglia exposed to lipopolysaccharide (LPS) was used for in vitro experiments. Microglial polarization was assessed by RT-PCR and immunostaining. Inflammatory cytokine assays and western blotting were used to investigate the molecular mechanisms underlying PTL-mediated microglial polarization in vivo and in vitro.

RESULTS

PTL significantly reduced cerebral infarction and neuronal apoptosis in rats with cerebral ischemia, reduced the level of inflammatory factors and alleviated neurological deficits. PTL treatment decreased the expression of microglia/macrophage markers in M1 macrophages and increased the expression of microglia/macrophage markers in M2 macrophages after stroke, which induced the transformation of microglia cells from the M1 phenotype to the M2 phenotype. Furthermore, PTL significantly reduced RhoA/ROCK-NF-κB pathway activity and downregulated the effects of pentanoic acid (ROCK agonist).

CONCLUSIONS

PTL has been shown to mediate neuroinflammation and protect against ischemic brain injury by regulating microglial polarization via the RhoA/ROCK pathway.