PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage–Induced Brain Injury. Issue 8 (August 2017)

• Record Type: Journal Article
• Authors: Han, Ranran; Luo, Jiaying; Shi, Yanchao; Yao, Yang; Hao, Junwei
• Is Part Of: Stroke. Volume 48:Issue 8(2017)
• Publication Date: 2017-08
• Subjects: cerebral hemorrhage -- hematoma -- inflammation -- PD-L1 -- stroke; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.117.016705
• Languages: English
• ISSNs: 0039-2499

Abstract

Abstract : Background and Purpose—: Intracerebral hemorrhage (ICH) is a neurologically destructive stroke, for which no valid treatment is available. This preclinical study examined the therapeutic effect of PD-L1 (programmed death ligand 1), a B7 family member and a ligand for both PD-1 (programmed death 1) and B7-1 (CD80), in a murine ICH model. Methods—: ICH was induced by injecting autologous blood into 252 male C57BL/6 and Rag1 −/− mice. One hour later, ICH mice were randomly assigned to receive an intraperitoneal injection of vehicle, PD-L1, or anti–PD-L1 antibody. Neurological function was assessed along with brain edema, brain infiltration of immune cells, blood–brain barrier integrity, neuron death, and mTOR (mammalian target of rapamycin) pathway products. Results—: PD-L1 significantly attenuated neurological deficits, reduced brain edema, and decreased hemorrhage volume in ICH mice. PD-L1 specifically downsized the number of brain-infiltrating CD4 + T cells and the percentages of Th1 and Th17 cells but increased the percentages of Th2 and regulatory T cells. In the PD-L1–treated group, we observed an amelioration of the inflammatory milieu, decreased cell death, and enhanced blood–brain barrier integrity. PD-L1 also inhibited the mTOR pathway. The administration of anti–PD-L1 antibody produced the opposite effects to those of PD-L1 in ICH mice. Conclusions—: PD-L1 provided protection from the damaging consequences of ICH. Abstract : Supplemental Digital Content is available in the text.