Post-ischemic inflammatory response in the brain: Targeting immune cell in ischemic stroke therapy

Abstract

An ischemic stroke occurs when the blood supply is obstructed to the vascular basin, causing the death of nerve cells and forming the ischemic core. Subsequently, the brain enters the stage of reconstruction and repair. The whole process includes cellular brain damage, inflammatory reaction, blood-brain barrier destruction, and nerve repair. During this process, the proportion and function of neurons, immune cells, glial cells, endothelial cells, and other cells change. Identifying potential differences in gene expression between cell types or heterogeneity between cells of the same type helps to understand the cellular changes that occur in the brain and the context of disease. The recent emergence of single-cell sequencing technology has promoted the exploration of single-cell diversity and the elucidation of the molecular mechanism of ischemic stroke, thus providing new ideas and directions for the diagnosis and clinical treatment of ischemic stroke.

Keywords: glial; immune cell; ischemic stroke; neuron; single-cell sequencing.

Figure 1

The inflammatory reaction of ischemic stroke. MG, microglia; Cxcr2, cxc chemokine receptor 2; Il1b, interleukin-1 beta; Mmp-9, matrix metallopeptidase 9; P2ry12, recombinant purinergic receptor P2Y, G protein poupled 12; Tmem119, transmembrane protein 119; Cx3cr1, c-x3-c motif chemokine receptor 1; Hexb, hexosaminidase subunit beta; Top2A, DNA topoisomerase II alpha; Stmn1, stathmin1; Mki67, marker of proliferation ki-67; TNF-α, tumor necrosis factor-α; IL-6, interleukin- 6; IL-2, interleukin-2; Cdk1, cyclin-dependent kinases 1; Cox7b, cytochrome c oxidase subunit 7b; Cox8a, cytochrome c oxidase subunit 8a; Uqcr11, ubiquinol-cytochrome c reductase, complex III subunit XI; H2-Aa, histocompatibility 2, class II antigen A, alpha; H2-Ab1, histocompatibility 2, class II antigen A, beta 1; Mrc1, mannose receptor C-Type 1; Cbr2, carbonyl reductase 2; NE, neutrophil; Wfdc17, WAP four-disulfide core domain 17; Ifitm1, interferon induced transmembrane protein 1; Fxyd5, FXYD Domain Containing Ion Transport Regulator 5; Rps27, Ribosomal Protein S27; Csf3r, colony stimulating factor 3 receptor; Chil3, Chitinase-3-like protein 3; Ltf, lactotransferrin; Lyz2, lysozyme 2; Cybb, cytochrome b-245 beta chain; Ly6g, lymphocyte antigen 6 complex locus G6D; NK, natural kill cell; Mono, monocyte; Ccrl2, c-c motif chemokine receptor like 2; Cxcl3, c-x-c motif chemokine ligand 3; Ccl7, c-c motif chemokine ligand 7; Ccl4, c-c motif chemokine ligand 4; Cdkn1a, cyclin dependent kinase inhibitor 1a. Figure was created with Biorender.com.

Figure 2

Blood–brain barrier disruption in ischemic stroke. EC, endothelial cell; IFIT3, interferon induced protein with tetratricopeptide repeats 3; Isg15, interferon-stimulated gene 15; USP18, ubiquitin-specific protease 18; Cyr61, cysteine-rich protein 61; Sgk3, serum and glucocorticoid induced kinase; MMP-9, matrix metallopeptidase 9; MMP-8, matrix metallopeptidase 8; NF-κB, nuclear factor kappa-B; NMDA receptor, N-methyl-D-aspartic acid receptor; BBB, blood–brain barrier. Figure was created with Biorender.com.

Figure 3

Nerve repair in ischemic stroke. MEGF10, multiple EGF like domains 10; MERTK, MER proto-oncogene, tyrosine kinase. Figure was created with Biorender.com.