Neuroinflammation and Brain-peripheral Interaction in Ischemic Stroke: A Narrative Review

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jan 23

PMID 36685518

Authors

Wenjing Cheng

Qing Zhao

Chengzhen Li

Yunzhi Xu

Affiliations

Soon will be listed here.

Abstract

Excessive immune activation within the lesion site can be observed after stroke onset. Such neuroinflammation within the brain parenchyma represents the innate immune response, as well as the result of the additional interactions between peripheral and resident immune cells. Accumulative studies have illustrated that the pathological process of ischemic stroke is associated with resident and peripheral immunity. The infiltration of peripheral immune cells within the brain parenchyma implicitly contributes to secondary brain injuries. Therefore, better understanding of the roles of resident and peripheral immune reactions toward ischemic insult is necessary. In this review, we summarized the interaction between peripheral and resident immunity on systemic immunity and the clinical outcomes after stroke onset and also discussed various potential immunotherapeutic strategies.

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References

Li S, Liu K, Gao Y, Zhao L, Zhang R, Fang H . Prognostic value of systemic immune-inflammation index in acute/subacute patients with cerebral venous sinus thrombosis. Stroke Vasc Neurol. 2020; 5(4):368-373. PMC: 7804059. DOI: 10.1136/svn-2020-000362. View

Hurn P, Subramanian S, Parker S, Afentoulis M, Kaler L, Vandenbark A . T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab. 2007; 27(11):1798-805. PMC: 2592689. DOI: 10.1038/sj.jcbfm.9600482. View

Gao Y, Chen T, Lei X, Li Y, Dai X, Cao Y . Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia/reperfusion injury. Mol Med Rep. 2016; 14(6):5481-5488. PMC: 5355690. DOI: 10.3892/mmr.2016.5936. View

Zhang A, Liu Y, Xu H, Zhang Z, Wang X, Yuan L . CCL17 exerts neuroprotection through activation of CCR4/mTORC2 axis in microglia after subarachnoid haemorrhage in rats. Stroke Vasc Neurol. 2022; . PMC: 9985806. DOI: 10.1136/svn-2022-001659. View

Jayaraj R, Azimullah S, Beiram R, Jalal F, Rosenberg G . Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation. 2019; 16(1):142. PMC: 6617684. DOI: 10.1186/s12974-019-1516-2. View

Malhotra K, Chang J, Khunger A, Blacker D, Switzer J, Goyal N . Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials. J Neurol. 2018; 265(8):1871-1879. DOI: 10.1007/s00415-018-8935-3. View

Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y . Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial. Eur J Neurol. 2009; 16(5):569-75. DOI: 10.1111/j.1468-1331.2009.02534.x. View

Nighoghossian N, Ovize M, Mewton N, Ong E, Cho T . Cyclosporine A, a Potential Therapy of Ischemic Reperfusion Injury. A Common History for Heart and Brain. Cerebrovasc Dis. 2016; 42(5-6):309-318. DOI: 10.1159/000446850. View

Kim E, Febbraio M, Bao Y, Tolhurst A, Epstein J, Cho S . CD36 in the periphery and brain synergizes in stroke injury in hyperlipidemia. Ann Neurol. 2012; 71(6):753-64. PMC: 3383818. DOI: 10.1002/ana.23569. View

10.

Nusrat L, Livingston-Thomas J, Raguthevan V, Adams K, Vonderwalde I, Corbett D . Cyclosporin A-Mediated Activation of Endogenous Neural Precursor Cells Promotes Cognitive Recovery in a Mouse Model of Stroke. Front Aging Neurosci. 2018; 10:93. PMC: 5928138. DOI: 10.3389/fnagi.2018.00093. View

11.

Lin D, Wang L, Yan S, Zhang Q, Zhang J, Shao A . The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression. Oxid Med Cell Longev. 2020; 2019:2491927. PMC: 7044480. DOI: 10.1155/2019/2491927. View

12.

Allen C, Thornton P, Denes A, McColl B, Pierozynski A, Monestier M . Neutrophil cerebrovascular transmigration triggers rapid neurotoxicity through release of proteases associated with decondensed DNA. J Immunol. 2012; 189(1):381-92. PMC: 3381844. DOI: 10.4049/jimmunol.1200409. View

13.

Fagan S, Cronic L, Hess D . Minocycline development for acute ischemic stroke. Transl Stroke Res. 2011; 2(2):202-8. PMC: 3169090. DOI: 10.1007/s12975-011-0072-6. View

14.

Yang F, Sun Y, Lu Q . The synergistic effect of minocycline and azole antifungal drugs against Scedosporium and Lomentospora species. BMC Microbiol. 2022; 22(1):21. PMC: 8753875. DOI: 10.1186/s12866-021-02433-6. View

15.

Chu H, Broughton B, Kim H, Lee S, Drummond G, Sobey C . Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization. Stroke. 2015; 46(7):1929-37. DOI: 10.1161/STROKEAHA.115.009426. View

16.

Brubaker A, Rendon J, Ramirez L, Choudhry M, Kovacs E . Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age. J Immunol. 2013; 190(4):1746-57. PMC: 3563860. DOI: 10.4049/jimmunol.1201213. View

17.

Cao X, Yang H, Liu X, Lou S, Kong L, Rong L . Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke. Neural Regen Res. 2022; 18(5):1033-1039. PMC: 9827769. DOI: 10.4103/1673-5374.355759. View

18.

Ye R, Yang Q, Kong X, Han J, Zhang X, Zhang Y . Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats. Neurochem Int. 2010; 58(3):391-8. DOI: 10.1016/j.neuint.2010.12.015. View

19.

Boutin H, LeFeuvre R, Horai R, Asano M, Iwakura Y, Rothwell N . Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci. 2001; 21(15):5528-34. PMC: 6762680. View

20.

Shiga Y, Onodera H, Matsuo Y, Kogure K . Cyclosporin A protects against ischemia-reperfusion injury in the brain. Brain Res. 1992; 595(1):145-8. DOI: 10.1016/0006-8993(92)91465-q. View