Nitro-oleic acid-mediated blood-brain barrier protection reduces ischemic brain injury.

Abstract

Nitro-oleic acid (OA-NO2), a nitroalkene formed in nitric oxide-dependent oxidative reactions, has been found in human plasma and is thought to regulate pathophysiological functions. Recently, accumulating evidence suggests that OA-NO2 may function as an anti-inflammatory mediator, and ameliorate the progression of diabetes and cardiovascular diseases. However, the role of OA-NO2 in ischemic brain injury remains unexplored. In this study, C57BL/6 mice were subjected to 1 h transient middle cerebral artery occlusion (MCAO) and followed by 1- 7 days of reperfusion. These mice were treated with vehicle, OA, or OA-NO2 (10 mg/kg) via tail vein injection at 2 h after the onset of MCAO. Our results show that intravenous administration of OA-NO2 led to reduced BBB leakage in ischemic brains, reduced brain infarct, and improved sensorimotor functions in response to ischemic insults when compared to OA and vehicle controls. Also, OA-NO2 significantly reduced BBB leakage-triggered infiltration of neutrophils and macrophages in the ischemic brains. Moreover, OA-NO2 treatment reduced the M1-type microglia and increased M2-type microglia. Mechanistically, OA-NO2 alleviated the decline of mRNA and protein level of major endothelial TJs including ZO-1 in stroke mice. Treatment of OA-NO2 also significantly inhibited stroke-induced inflammatory mediators, iNOS, E-selectin, P-selectin, and ICAM1, in mouse brains. In conclusion, OA-NO2 preserves BBB integrity and confers neurovascular protection in ischemic brain damage. OA-NO2-mediated brain protection may help us to develop a novel therapeutic strategy for the treatment of ischemic stroke.

• Authors: Chao Zhou, Moxi Su, Ping Sun, Xuelian Tang, Ke-Jie Yin
• Journal: Experimental neurology (Exp Neurol) Vol. 346 Pg. 113861 (12 2021) ISSN: 1090-2430 [Electronic] United States
• PMID: 34499902 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Nitro Compounds
• Oleic Acids
• CXA-10

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Blood-Brain Barrier (drug effects, metabolism)
• Brain Injuries (drug therapy, metabolism)
• Brain Ischemia (drug therapy, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nitro Compounds (administration & dosage)
• Oleic Acids (administration & dosage)