Effects of Microglial Activation and Polarization on Brain Injury After Stroke

Overview

Journal Front Neurol

Specialty Neurology

Date 2021 Jul 19

PMID 34276530

Citations 39

Authors

Rui Dong

Renxuan Huang

Jiaoqi Wang

Hongyu Liu

Zhongxin Xu

Affiliations

Soon will be listed here.

Abstract

Stroke is one of the most common causes of death worldwide. The subsequent development of neuroinflammation and brain edema dramatically increases the risks associated with stroke, leading to a substantial increase in mortality. Although considerable progress has been made in improving cerebral perfusion in the acute phase of stroke, effective treatment options for the subacute and chronic phases associated with cerebral infarction are limited. Microglia, the innate immune cells of the central nervous system (CNS), can be activated and polarized to take on different phenotypes in response to stimulations associated with stroke, including pro-inflammatory and anti-inflammatory phenotypes, which affect the prognosis of stroke. Therefore, investigation of the activation and polarizing mechanisms of microglia plays a critical role in treating stroke. The aim of this article was to investigate the significance of microglial phenotype regulation in stroke treatment by summarizing the activation, polarizing mechanisms, and general microglia characteristics.

Citing Articles

Therapeutic Potential of TPT-260 in Ischemic Stroke: An Investigation Into Its Anti-Inflammatory Effects and Impact on Microglial Activation.

Qian J, Guo X, Xu Q, Huang Z J Inflamm Res. 2025; 18:3055-3066.

PMID: 40046681 PMC: 11881767. DOI: 10.2147/JIR.S497030.

Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity.

Clain J, Couret D, Bringart M, Meilhac O, Lefebvre dHellencourt C, Diotel N IBRO Neurosci Rep. 2025; 18():16-30.

PMID: 39816479 PMC: 11733059. DOI: 10.1016/j.ibneur.2024.12.002.

Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke.

Ma B, Chan T, Lo B Surg Neurol Int. 2024; 15:394.

PMID: 39640340 PMC: 11618647. DOI: 10.25259/SNI_703_2024.

Neuroprotective Potential of Glycyrrhizic Acid in Ischemic Stroke: Mechanisms and Therapeutic Prospects.

Li Y, Wu J, Du F, Tang T, Lim J, Karuppiah T Pharmaceuticals (Basel). 2024; 17(11).

PMID: 39598404 PMC: 11597102. DOI: 10.3390/ph17111493.

Artificial Microglia Nanoplatform Loaded With Anti-RGMa in Acoustic/Magnetic Feld for Recanalization and Neuroprotection in Acute Ischemic Stroke.

Cheng R, Luo X, Wu X, Wang Z, Chen Z, Zhang S Adv Sci (Weinh). 2024; 11(48):e2410529.

PMID: 39475454 PMC: 11672321. DOI: 10.1002/advs.202410529.

References

Satoh T, McKercher S, Lipton S . Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs. Free Radic Biol Med. 2013; 65:645-657. PMC: 3859717. DOI: 10.1016/j.freeradbiomed.2013.07.022. View

Higashi Y, Aratake T, Shimizu S, Shimizu T, Nakamura K, Tsuda M . Influence of extracellular zinc on M1 microglial activation. Sci Rep. 2017; 7:43778. PMC: 5327400. DOI: 10.1038/srep43778. View

Bodhankar S, Lapato A, Chen Y, Vandenbark A, Saugstad J, Offner H . Role for microglia in sex differences after ischemic stroke: importance of M2. Metab Brain Dis. 2015; 30(6):1515-29. PMC: 4644102. DOI: 10.1007/s11011-015-9714-9. View

Lin S, Yin Q, Zhong Q, Lv F, Zhou Y, Li J . Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage. J Neuroinflammation. 2012; 9:46. PMC: 3344687. DOI: 10.1186/1742-2094-9-46. View

Wang P, Fang H, Chen J, Lin S, Liu Y, Xiong X . Polyinosinic-polycytidylic acid has therapeutic effects against cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via TLR3. J Immunol. 2014; 192(10):4783-94. PMC: 4009499. DOI: 10.4049/jimmunol.1303108. View

Walker F, Beynon S, Jones K, Zhao Z, Kongsui R, Cairns M . Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms. Brain Behav Immun. 2014; 37:1-14. DOI: 10.1016/j.bbi.2013.12.010. View

Wang Y, Wang P, Fang H, Chen J, Xiong X, Yang Q . Toll-like receptor 4 antagonist attenuates intracerebral hemorrhage-induced brain injury. Stroke. 2013; 44(9):2545-52. DOI: 10.1161/STROKEAHA.113.001038. View

Chen J, Yin W, Tu Y, Wang S, Yang X, Chen Q . L-F001, a novel multifunctional ROCK inhibitor, suppresses neuroinflammation in vitro and in vivo: Involvement of NF-κB inhibition and Nrf2 pathway activation. Eur J Pharmacol. 2017; 806:1-9. DOI: 10.1016/j.ejphar.2017.03.025. View

Moretti R, Leger P, Besson V, Csaba Z, Pansiot J, Di Criscio L . Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain. J Neuroinflammation. 2016; 13(1):95. PMC: 4850658. DOI: 10.1186/s12974-016-0560-4. View

10.

Pan J, Jin J, Ge H, Yin K, Chen X, Han L . Malibatol A regulates microglia M1/M2 polarization in experimental stroke in a PPARγ-dependent manner. J Neuroinflammation. 2015; 12:51. PMC: 4378556. DOI: 10.1186/s12974-015-0270-3. View

11.

Lauro C, Catalano M, Trettel F, Limatola C . Fractalkine in the nervous system: neuroprotective or neurotoxic molecule?. Ann N Y Acad Sci. 2015; 1351:141-8. DOI: 10.1111/nyas.12805. View

12.

Liu L, Liu X, Wang R, Yan F, Luo Y, Chandra A . Mild focal hypothermia regulates the dynamic polarization of microglia after ischemic stroke in mice. Neurol Res. 2018; 40(6):508-515. DOI: 10.1080/01616412.2018.1454090. View

13.

Dang J, Mitkari B, Kipp M, Beyer C . Gonadal steroids prevent cell damage and stimulate behavioral recovery after transient middle cerebral artery occlusion in male and female rats. Brain Behav Immun. 2011; 25(4):715-26. DOI: 10.1016/j.bbi.2011.01.013. View

14.

Hua K, Sheng X, Li T, Wang L, Zhang Y, Huang Z . The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats. Acta Pharmacol Sin. 2015; 36(8):917-27. PMC: 4564877. DOI: 10.1038/aps.2015.31. View

15.

Hua K, Schindler M, McQuail J, Forbes M, Riddle D . Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats. PLoS One. 2013; 7(12):e52728. PMC: 3530502. DOI: 10.1371/journal.pone.0052728. View

16.

Hughes P, Allegrini P, Rudin M, Perry V, Mir A, Wiessner C . Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab. 2002; 22(3):308-17. DOI: 10.1097/00004647-200203000-00008. View

17.

von Bernhardi R, Eugenin-von Bernhardi L, Eugenin J . Microglial cell dysregulation in brain aging and neurodegeneration. Front Aging Neurosci. 2015; 7:124. PMC: 4507468. DOI: 10.3389/fnagi.2015.00124. View

18.

Tian X, Liu H, Xiang F, Xu L, Dong Z . β-Caryophyllene protects against ischemic stroke by promoting polarization of microglia toward M2 phenotype via the TLR4 pathway. Life Sci. 2019; 237:116915. DOI: 10.1016/j.lfs.2019.116915. View

19.

Pang L, Ye W, Che X, Roessler B, Betz A, Yang G . Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-ss1 expression. Stroke. 2001; 32(2):544-52. DOI: 10.1161/01.str.32.2.544. View

20.

Takeuchi O, Akira S . Pattern recognition receptors and inflammation. Cell. 2010; 140(6):805-20. DOI: 10.1016/j.cell.2010.01.022. View