Related Experiment Video
Updated: Sep 2, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via
Yehao Zhang1, Lan Miao1, Qing Peng1
1Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing key Laboratory of pharmacology of Chinese Materia Region, Beijing 100091, PR China.
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.
Insights
Parthenolide (PTL) reduces brain damage after stroke by shifting microglia from M1 to M2 phenotypes. This neuroprotective effect involves regulating the RhoA/ROCK pathway, offering a potential therapeutic strategy for ischemic brain injury.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia play dual roles in stroke, exhibiting proinflammatory (M1) and anti-inflammatory (M2) phenotypes.
- Parthenolide (PTL) demonstrates anti-inflammatory and neuroprotective effects in neurological diseases.
- The precise mechanisms of PTL's action in stroke-induced neuroinflammation remain to be fully elucidated.
Purpose of the Study:
- To investigate the effect of Parthenolide (PTL) on microglial polarization following ischemic stroke.
- To identify the molecular targets through which PTL influences microglial polarization.
Main Methods:
- Established a focal transient cerebral ischemia rat model, employing TTC and HE staining for infarct and tissue damage assessment.
- Utilized in vitro human microglia models exposed to lipopolysaccharide (LPS) for mechanistic studies.
- Assessed microglial polarization using RT-PCR and immunostaining, and investigated molecular pathways via inflammatory cytokine assays and western blotting.
Main Results:
- PTL treatment significantly reduced cerebral infarction volume, neuronal apoptosis, and neurological deficits in ischemic rats.
- PTL promoted a shift in microglial polarization from M1 to M2 phenotypes, indicated by altered marker expression.
- PTL suppressed the RhoA/ROCK-NF-κB signaling pathway activity.
Conclusions:
- Parthenolide (PTL) exerts neuroprotective effects against ischemic brain injury by modulating microglial polarization.
- The RhoA/ROCK pathway is identified as a key molecular target for PTL-induced microglial polarization and subsequent neuroprotection.
