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Fasudil alleviates cerebral ischemia‑reperfusion injury by inhibiting inflammation and improving neurotrophic factor
Min-Fang Guo1, Hui-Yu Zhang1, Pei-Jun Zhang1
1Institute of Brain Science, Shanxi Datong University, Datong, China.
Abstract:
The Rho kinase inhibitor fasudil exerts neuroprotective effects. We previously showed that fasudil can regulate M1/M2 microglia polarization and inhibit neuroinflammation. Here, the therapeutic effect of fasudil on cerebral ischemia‑reperfusion (I/R) injury was investigated using the middle cerebral artery occlusion and reperfusion (MCAO/R) model in Sprague‑Dawley rats. The effect of fasudil on the phenotype of microglia and neurotrophic factors in the I/R brain and its potential molecular mechanism was also explored. It was found that fasudil ameliorated neurological deficits, neuronal apoptosis, and inflammatory response in rats with cerebral I/R injury. Fasudil also promoted the polarization of microglia into the M2 phenotype, in turn promoting the secretion of neurotrophic factors. Furthermore, fasudil significantly inhibited the expression of TLR4 and NF‑κB. These findings suggest that fasudil could inhibit the neuroinflammatory response and reduce brain injury after I/R injury by regulating the shift of microglia from an inflammatory M1 phenotype to an anti‑inflammatory M2 phenotype, which may be related to the regulation of the TLR4/ NF‑κB signal pathway.
Insights
Fasudil, a Rho kinase inhibitor, reduces brain damage from cerebral ischemia-reperfusion injury. It shifts microglia to an anti-inflammatory M2 phenotype, decreasing neuroinflammation and promoting recovery.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Cerebral ischemia-reperfusion (I/R) injury triggers significant neuroinflammation.
- Microglia polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes plays a critical role in I/R injury.
- Fasudil, a Rho kinase inhibitor, has demonstrated neuroprotective and anti-inflammatory properties.
Purpose of the Study:
- To investigate the therapeutic effects of fasudil on cerebral I/R injury in a rat model.
- To explore fasudil's impact on microglia polarization and neurotrophic factor secretion.
- To elucidate the molecular mechanisms underlying fasudil's neuroprotective actions.
Main Methods:
- Middle cerebral artery occlusion and reperfusion (MCAO/R) model in Sprague-Dawley rats.
- Administration of fasudil to assess its effects on neurological deficits, neuronal apoptosis, and inflammatory markers.
- Analysis of microglia phenotype (M1/M2 polarization) and neurotrophic factor levels.
- Investigation of the Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) signaling pathways.
Main Results:
- Fasudil treatment significantly ameliorated neurological deficits and reduced neuronal apoptosis in MCAO/R rats.
- Fasudil promoted the M2 microglia polarization, leading to increased secretion of neurotrophic factors.
- Fasudil administration inhibited the expression of TLR4 and NF-κB signaling molecules.
Conclusions:
- Fasudil exerts neuroprotective effects against cerebral I/R injury by modulating microglia polarization from M1 to M2 phenotype.
- This shift in microglia phenotype reduces neuroinflammation and promotes the release of beneficial neurotrophic factors.
- The therapeutic mechanism of fasudil may involve the regulation of the TLR4/NF-κB signaling pathway.
