Interventions in Ischemic Stroke Targeting Microglial Activation

Ziqin Wang

doi:10.54254/2753-8818/3/20220179

Research Article

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Published on 28 April 2023

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Wang,Z. (2023). Interventions in Ischemic Stroke Targeting Microglial Activation. Theoretical and Natural Science,3,63-70.

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Interventions in Ischemic Stroke Targeting Microglial Activation

Ziqin Wang *^,1,

¹ Division of Natural and Applied Sciences, Duke Kunshan University, Kunshan, Jiangsu, 215316, China

* Author to whom correspondence should be addressed.

https://doi.org/10.54254/2753-8818/3/20220179

Abstract

Ischemic stroke is one of the biggest health concerns nowadays, leading to nonnegligible disability and mortality in its patients. During its pathological development, resident microglia in the central nervous system play a significant role to repair the damage, but may also expand the lesion because of the excessive microglial activation. As a result, microglial activation is considered a potential therapeutic target for ischemic stroke. Since microglia polarized into different phenotypes ranging from M1 to M2 display proinflammatory and neuroprotective functions, regulation of the morpho-functional change of microglia became a further way of intervention in ischemic stroke. This review qualitatively analyses drugs for ischemic stroke that were studied by credible research in the recent ten years in terms of experimental methods, applied animal models, and potential signaling pathways, so as to provide clues for future studies on the fine regulation of microglial activation to treat ischemic stroke.

Keywords

ischemic stroke, microglial activation, microglial polarization, treatment

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References

[1]. Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., Elkind, M. S. V., Evenson, K. R., Eze-Nliam, C., Ferguson, J. F., Generoso, G., Ho, J. E., Kalani, R., Khan, S. S., Kissela, B. M., . . . American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. (2022). Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association. Circulation, 145(8), e153-e639. https://doi.org/10.1161/CIR.0000000000001052

[2]. Yao, Y., Wei, Z., Zhang, Y., Li, X., Gong, L., Zhou, J., Wang, Y., Zhang, Y., & Wang, R. (2021). Functional Disability After Ischemic Stroke: A Community-Based Cross-Sectional Study in Shanghai, China [Original Research]. Frontiers in Neurology, 12. https://doi.org/10.3389/fneur.2021.649088

[3]. GBD 2016 Lifetime Risk of Stroke Collaborators. (2018). Global, Regional, and Country- Specific Lifetime Risks of Stroke, 1990 and 2016. New England Journal of Medicine, 379(25), 2429-2437. https://doi.org/10.1056/NEJMoa1804492

[4]. Jayaraj, R. L., Azimullah, S., Beiram, R., Jalal, F. Y., & Rosenberg, G. A. (2019). Neuroinflammation: friend and foe for ischemic stroke. Journal of Neuroinflammation, 16(1), 142. https://doi.org/10.1186/s12974-019-1516-2

[5]. Zhang, C., Zhu, Y., Wang, S., Zachory Wei, Z., Jiang, M. Q., Zhang, Y., Pan, Y., Tao, S., Li, J., & Wei, L. (2018). Temporal Gene Expression Profiles after Focal Cerebral Ischemia in Mice. Aging and Disease, 9(2), 249-261. https://doi.org/10.14336/AD.2017.0424

[6]. Aguzzi, A., Barres, B. A., & Bennett, M. L. (2013). Microglia: Scapegoat, Saboteur, or Something Else? Science, 339(6116), 156-161. https://doi.org/10.1126/science.1227901

[7]. Crain, J. M., Nikodemova, M., & Watters, J. J. (2013). Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice. Journal of Neuroscience Research, 91(9), 1143-1151. https://doi.org/10.1002/jnr.23242

[8]. Chen, A., Fang, Z., Chen, X., Yang, S., Zhou, Y., Mao, L., Xia, Y., Jin, H., Li, Y., You, M., Wang, X., Lei, H., He, Q., & Hu, B. (2019). Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke. Cell Death & Disease, 10(7), 487. https://doi.org/10.1038/s41419-019-1716-9

[9]. Lopes, R. S., Cardoso, M. M., Sampaio, A. O., Barbosa, M. S., Souza, C. C., da Silva, M. C., Ferreira, E. M. N., Freire, M. A. M., Lima, R. R., & Gomes-Leal, W. (2016). Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia. Journal of Biosciences, 41(3), 381-394. https://doi.org/10.1007/s12038-016-9621-1

[10]. Kluge, M. G., Abdolhoseini, M., Zalewska, K., Ong, L. K., Johnson, S. J., Nilsson, M., & Walker, F. R. (2019). Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke. J Cereb Blood Flow Metab, 39(12), 2456- 2470. https://doi.org/10.1177/0271678x18797346

[11]. Shi, Q., Wang, H., Liu, Z., Fang, S., Song, X., Lu, Y., Zhang, W., Sa, X., Ying, H., & Wei, E. (2015). HAMI 3379, a CysLT2R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats. Neuroscience, 291, 53-69. https://doi.org/10.1016/j.neuroscience.2015.02.002

[12]. Hu, X., Li, P., Guo, Y., Wang, H., Leak, R. K., Chen, S., Gao, Y., & Chen, J. (2012). Microglia/Macrophage Polarization Dynamics Reveal Novel Mechanism of Injury Expansion After Focal Cerebral Ischemia. Stroke, 43(11), 3063-3070. https://doi.org/10.1161/STROKEAHA.112.659656

[13]. Suenaga, J., Hu, X., Pu, H., Shi, Y., Hassan, S. H., Xu, M., Leak, R. K., Stetler, R. A., Gao, Y., & Chen, J. (2015). White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke. Experimental Neurology, 272, 109-119. https://doi.org/10.1016/j.expneurol.2015.03.021

[14]. Nowicka, D., Rogozinska, K., Aleksy, M., Witte, O. W., & Skangiel-Kramska, J. (2008). Spatiotemporal dynamics of astroglial and microglial responses after photothrombotic stroke in the rat brain. Acta Neurobiologiae Experimentalis, 68(2), 155-168.

[15]. Potey, C., Ouk, T., Petrault, O., Petrault, M., Berezowski, V., Salleron, J., Bordet, R., & Gautier, S. (2015). Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia. British Journal of Pharmacology, 172(21), 5188- 5198. https://doi.org/10.1111/bph.13285

[16]. Zhang, X., Zhu, X., Ji, B., Cao, X., Yu, L., Zhang, Y., Bao, X., Xu, Y., & Jin, J. (2019). LncRNA-1810034E14Rik reduces microglia activation in experimental ischemic stroke. Journal of Neuroinflammation, 16(1), 75. https://doi.org/10.1186/s12974-019-1464-x

[17]. Higashi, Y., Aratake, T., Shimizu, S., Shimizu, T., Nakamura, K., Tsuda, M., Yawata, T., Ueba, T., & Saito, M. (2017). Influence of extracellular zinc on M1 microglial activation. Scientific Reports, 7(1), 43778. https://doi.org/10.1038/srep43778

[18]. Liu, C., Liu, S., Xiong, L., Zhang, L., Li, X., Cao, X., Xue, J., Li, L., Huang, C., & Huang, Z. (2021). Genistein-3′-sodium sulfonate Attenuates Neuroinflammation in Stroke Rats by Down-Regulating Microglial M1 Polarization through α 7nAChR-NF- κ B Signaling Pathway [Research Paper]. International Journal of Biological Sciences, 17(4), 1088-1100. https://doi.org/10.7150/ijbs.56800

[19]. Liu, S., Su, Y., Sun, B., Hao, R., Pan, S., Gao, X., Dong, X., Ismail, A. M., & Han, B. (2020). Luteolin Protects Against CIRI, Potentially via Regulation of the SIRT3/AMPK/mTOR Signaling Pathway. Neurochemical Research, 45(10), 2499-2515. https://doi.org/10.1007/s11064-020-03108-w

[20]. Liu, J., Veldeman, M., Höllig, A., Nolte, K., Liebenstund, L., Willuweit, A., Langen, K.-J., Rossaint, R., & Coburn, M. (2022). Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO). Scientific Reports, 12(1), 691. https://doi.org/10.1038/s41598-021-04666-x

[21]. Jin, Q., Cheng, J., Liu, Y., Wu, J., Wang, X., Wei, S., Zhou, X., Qin, Z., Jia, J., & Zhen, X. (2014). Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke. Brain, Behavior, and Immunity, 40, 131- 142. https://doi.org/https://doi.org/10.1016/j.bbi.2014.03.003

[22]. Qin, C., Fan, W., Liu, Q., Shang, K., Murugan, M., Wu, L., Wang, W., & Tian, D. (2017). Fingolimod Protects Against Ischemic White Matter Damage by Modulating Microglia Toward M2 Polarization via STAT3 Pathway. Stroke, 48(12), 3336-3346. https://doi.org/10.1161/STROKEAHA.117.018505

[23]. Lu, Y., Zhou, M., Li, Y., Li, Y., Hua, Y., & Fan, Y. (2021). Minocycline promotes functional recovery in ischemic stroke by modulating microglia polarization through STAT1/STAT6 pathways. Biochemical Pharmacology, 186, 114464. https://doi.org/10.1016/j.bcp.2021.114464

[24]. Yang, S., Wang, H., Yang, Y., Wang, R., Wang, Y., Wu, C., & Du, G. (2019). Baicalein administered in the subacute phase ameliorates ischemia-reperfusion-induced brain injury by reducing neuroinflammation and neuronal damage. Biomedicine & Pharmacotherapy, 117, 109102. https://doi.org/10.1016/j.biopha.2019.109102

[25]. Shin, J. A., Lim, S. M., Jeong, S. I., Kang, J. L., & Park, E.-M. (2014). Noggin improves ischemic brain tissue repair and promotes alternative activation of microglia in mice. Brain, Behavior, and Immunity, 40, 143-154. https://doi.org/10.1016/j.bbi.2014.03.013

[26]. Wang, R., Li, J., Duan, Y., Tao, Z., Zhao, H., & Luo, Y. (2017). Effects of Erythropoietin on Gliogenesis during Cerebral Ischemic/Reperfusion Recovery in Adult Mice. Aging and Disease, 8(4), 410-419. https://doi.org/10.14336/ad.2016.1209

[27]. Li, C., Zhao, Z., Luo, Y., Ning, T., Liu, P., Chen, Q., Chu, Y., Guo, Q., Zhang, Y., Zhou, W., Chen, H., Zhou, Z., Wang, Y., Su, B., You, H., Zhang, T., Li, X., Song, H., Li, C., . . . Jiang, C. (2021). Macrophage-Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke. Advanced Science (Weinheim, Baden-Wurttemberg, Germany), 8(20), e2101526-e2101526. https://doi.org/10.1002/advs.202101526

[28]. Morganti, J. M., Riparip, L.-K., & Rosi, S. (2016). Call Off the Dog(ma): M1/M2 Polarization Is Concurrent following Traumatic Brain Injury. PLOS ONE, 11(1), e0148001. https://doi.org/10.1371/journal.pone.0148001

[29]. Stratoulias, V., Venero, J. L., Tremblay, M.-È., & Joseph, B. (2019). Microglial subtypes: diversity within the microglial community. The EMBO Journal, 38(17), e101997. https://doi.org/10.15252/embj.2019101997

[30]. Najafi, A. R., Crapser, J., Jiang, S., Ng, W., Mortazavi, A., West, B. L., & Green, K. N. (2018). A limited capacity for microglial repopulation in the adult brain. Glia, 66(11), 2385-2396. https://doi.org/10.1002/glia.23477

[31]. Zhang, F., Nance, E., Alnasser, Y., Kannan, R., & Kannan, S. (2016). Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation. Journal of Neuroinflammation, 13(1), 65. https://doi.org/10.1186/s12974-016-0529-3

[32]. Lana, D., Melani, A., Pugliese, A. M., Cipriani, S., Nosi, D., Pedata, F., & Giovannini, M. G. (2014). The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole [Original Research]. Frontiers in Aging Neuroscience, 6. https://doi.org/10.3389/fnagi.2014.00322

[33]. Sandoval, K. E., & Witt, K. A. (2008). Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiology of Disease, 32(2), 200-219. https://doi.org/10.1016/j.nbd.2008.08.005

Cite this article

Wang,Z. (2023). Interventions in Ischemic Stroke Targeting Microglial Activation. Theoretical and Natural Science,3,63-70.

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About volume

Volume title: Proceedings of the 2nd International Conference on Biological Engineering and Medical Science (ICBioMed 2022), Part I

Conference website: http://www.icbiomed.org

ISBN：978-1-915371-25-6(Print) / 978-1-915371-26-3(Online)

Conference date: 7 November 2022

Editor：Gary Royle, Steven M. Lipkin

Series: Theoretical and Natural Science

Volume number: Vol.3

ISSN：2753-8818(Print) / 2753-8826(Online)

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