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Updated: Jun 26, 2025

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
The Roles of RhoA/ROCK/NF-κB Pathway in Microglia Polarization Following Ischemic Stroke
Weizhuo Lu1,2, Yilin Wang1, Jiyue Wen3
1Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Abstract:
Ischemic stroke is the leading cause of death and disability worldwide. Nevertheless, there still lacks the effective therapies for ischemic stroke. Microglia are resident macrophages of the central nervous system (CNS) and can initiate immune responses and monitor the microenvironment. Microglia are activated and polarize into proinflammatory or anti‑inflammatory phenotype in response to various brain injuries, including ischemic stroke. Proinflammatory microglia could generate immunomodulatory mediators, containing cytokines and chemokines, these mediators are closely associated with secondary brain damage following ischemic stroke. On the contrary, anti-inflammatory microglia facilitate recovery following stroke. Regulating the activation and the function of microglia is crucial in exploring the novel treatments for ischemic stroke patients. Accumulating studies have revealed that RhoA/ROCK pathway and NF-κB are famous modulators in the process of microglia activation and polarization. Inhibiting these key modulators can promote the polarization of microglia to anti-inflammatory phenotype. In this review, we aimed to provide a comprehensive overview on the role of RhoA/ROCK pathway and NF-κB in the microglia activation and polarization, reveal the relationship between RhoA/ROCK pathway and NF-κB in the pathological process of ischemic stroke. In addition, we likewise discussed the drug modulators targeting microglia polarization.
Insights
Targeting microglia polarization via RhoA/ROCK and NF-κB pathways offers a promising therapeutic strategy for ischemic stroke. Inhibiting these pathways promotes beneficial anti-inflammatory microglia, aiding recovery from this leading cause of disability.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Ischemic stroke is a major global health concern with limited effective treatments.
- Microglia, the central nervous system's immune cells, play a dual role in stroke, with proinflammatory types exacerbating damage and anti-inflammatory types promoting recovery.
- Understanding microglia activation and polarization is key to developing novel stroke therapies.
Purpose of the Study:
- To provide a comprehensive overview of the RhoA/ROCK pathway and NF-κB in microglia activation and polarization.
- To elucidate the relationship between RhoA/ROCK and NF-κB in ischemic stroke pathology.
- To discuss therapeutic modulators targeting microglia polarization for ischemic stroke.
Main Methods:
- Literature review focusing on the roles of RhoA/ROCK and NF-κB pathways.
- Analysis of studies on microglia activation and polarization in the context of ischemic stroke.
- Examination of existing and potential drug targets for modulating microglia phenotype.
Main Results:
- The RhoA/ROCK pathway and NF-κB are critical regulators of microglia activation and polarization.
- Inhibition of these pathways can steer microglia towards a neuroprotective, anti-inflammatory phenotype.
- These pathways are interconnected in the pathological processes following ischemic stroke.
Conclusions:
- Modulating microglia polarization through targeting the RhoA/ROCK pathway and NF-κB presents a viable therapeutic avenue for ischemic stroke.
- Further research into drug modulators targeting these pathways could lead to effective treatments for stroke patients.
- Understanding the interplay between RhoA/ROCK and NF-κB is crucial for advancing stroke therapy.

