Neutrophil-derived cathelicidin promotes cerebral angiogenesis after ischemic stroke

Author:

Xie Wanqing1,Huang Tingting1,Guo Yunlu1,Zhang Yueman1,Chen Weijie1,Li Yan1,Chen Chen1,Li Peiying1ORCID

Affiliation:

1. Department of Anesthesiology, Key Laboratory of the Ministry of Education of Anesthesia Medicine, Clinical Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Abstract

Neutrophils play critical roles in the evolving of brain injuries following ischemic stroke. However, how they impact the brain repair in the late phase after stroke remain uncertain. Using a prospective clinical stroke patient cohort, we found significantly increased cathelicidin antimicrobial peptide (CAMP) in the peripheral blood of stroke patients compared to that of healthy controls. While in the mouse stroke model, CAMP was present in the peripheral blood, brain ischemic core and significantly increased at day 1, 3, 7, 14 after middle cerebral artery occlusion (MCAO). CAMP−/− mice exhibited significantly increased infarct volume, exacerbated neurological outcome, reduced cerebral endothelial cell proliferation and vascular density at 7 and 14 days after MCAO. Using bEND3 cells subjected to oxygen-glucose deprivation (OGD), we found significantly increased angiogenesis-related gene expression with the treatment of recombinant CAMP peptide (rCAMP) after reoxygenation. Intracerebroventricular injection (ICV) of AZD-5069, the antagonist of CAMP receptor CXCR2, or knockdown of CXCR2 by shCXCR2 recombinant adeno-associated virus (rAAV) impeded angiogenesis and neurological recovery after MCAO. Administration of rCAMP promoted endothelial proliferation and angiogenesis and attenuated neurological deficits 14 days after MCAO. In conclusion, neutrophil derived CAMP represents an important mediator that could promote post-stroke angiogenesis and neurological recovery in the late phase after stroke.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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