PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage-Induced Brain Injury.

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.

• Authors: Ranran Han, Jiaying Luo, Yanchao Shi, Yang Yao, Junwei Hao
• Journal: Stroke (Stroke) Vol. 48 Issue 8 Pg. 2255-2262 (08 2017) ISSN: 1524-4628 [Electronic] United States
• PMID: 28706113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 American Heart Association, Inc.

Chemical References

• B7-H1 Antigen
• Cd274 protein, mouse
• Neuroprotective Agents

Topics

• Animals
• B7-H1 Antigen (administration & dosage)
• Blood-Brain Barrier (drug effects, immunology, pathology)
• Brain Injuries (immunology, pathology, prevention & control)
• Cerebral Hemorrhage (immunology, pathology, prevention & control)
• Disease Models, Animal
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neuroprotective Agents (administration & dosage)
• T-Lymphocytes, Regulatory (drug effects, immunology)