Abstract 18: A Novel Neutrophil Subpopulation Mediates Neuroprotection In The Late Phases Of Cerebral Ischemia

• DOI: 10.1161/str.54.suppl_1.18
• Publication Date: 2023-02-02T10:16:12Z
• Authors: Lidia Garcia-Bonilla; Rose Sciortino; Gianfranco M Racc...; Costantino Iadecola; Josef Anrather
• Keywords: Infiltration (HVAC); Brain ischemia

Cerebral ischemia triggers a powerful inflammatory reaction involving infiltration of peripheral leukocytes. Neutrophils, the first immune cells entering ischemic brain, contribute to brain injury by limiting tissue perfusion and destabilizing blood-brain barrier. However, recent evidence indicates that neutrophils can also participate repairing process. Nevertheless, dynamics complexity neutrophil subsets are poorly understood. Here, we performed single-cell transcriptomics obtain picture infiltrating diversity in mouse 2 (D02) 14 days (D14) after transient middle cerebral artery occlusion (MCAo) or sham surgery (Sham). Clustering analysis transcripts revealed 5 populations. In Sham, most fell into clusters 1 4, characterized expression genes associated with development such Retnlg Mmp8 (cluster 1) Camp, Ltf, Chil3 Lcn2 4). After MCAo, 4 gradually decreased, whereas cluster 2, identified type I response ( Isg15, Ifit3, Rsad2, Ifit1, Ifi204 ) 3, upregulation chemokines/cytokines Ccl3 , Ccl4 Csf1 ), increased progressively from D02 D14. Interestingly, found number was times higher at D14 than (Sham, 0.2 ± 0.1 x10 3 ; D02: 1.3 D14: 14.5 3.5x10 cells; p=0.02 vs D14; n=10-14/group). Therefore, next investigated if has beneficial adverse effect on stroke recovery. To this end, 7 depletion induced systemic injection both rat anti-Ly6G (50μg/mouse, i.p) CXCR2-antagonist SB225002 (2 mg/kg, i.p), once per day, for consecutive days. We loss (-18.7 2.9 -8 2.6% IgG/vehicle mice; p=0.01; n=9/group). addition, decreased ambulatory distance (p<0.05 vehicle; n=11/group) stereotypic behavior without altering open field performance mice. Our study unveils an unrecognized subpopulation protecting subacute phase, opening new avenues treatment.