Orexin-A inhibits cerebral ischaemic inflammatory injury mediated by the nuclear factor-κB signalling pathway and alleviates stroke-induced immunodepression in mice.

Abstract

Cerebral ischaemia is accompanied by infectious complications due to immunosuppression, known as stroke-induced immunodepression (SIID). Orexin-A (OXA), a neuropeptide produced in the hypothalamus, has been reported to have neuroprotective properties after stroke and is known to modulate inflammatory processes in peripheral tissues. The aim of this study was to determine the effects of orexin-A (OXA) on cerebral ischaemic inflammatory injury and SIID following experimental stroke. Cerebral ischaemia was induced in C57/BL6 mice by middle cerebral artery occlusion (MCAO). A mouse model of pneumonia and poststroke pneumococcal pneumonia was established by intratracheal inoculation with S. pneumoniae in a normal mouse or MCAO mouse model on the third day. We found that OXA postconditioning inhibited cerebral ischaemic inflammatory injury. The mechanism involved downregulation of the NF-κB signalling pathway. In addition, OXA may serve as a potential treatment target for attenuating stroke-induced immunodepression in mice.

• Authors: Dong Zhao, Zhaofu Zeng, Huaheng Mo, Weihua Hu, Sumei Tian, Die Hu, Lin Gong, Ke Hu
• Journal: Brain research bulletin (Brain Res Bull) Vol. 174 Pg. 296-304 (09 2021) ISSN: 1873-2747 [Electronic] United States
• PMID: 34216650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• NF-kappa B
• Neuroprotective Agents
• Rela protein, mouse
• Transcription Factor RelA

Topics

• Animals
• Brain Ischemia (drug therapy)
• Encephalitis (drug therapy)
• Immune Tolerance (drug effects)
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (drug effects)
• Neuroprotective Agents (therapeutic use)
• Pneumococcal Infections (complications, drug therapy, pathology)
• Signal Transduction (drug effects)
• Stroke (drug therapy, immunology)
• Transcription Factor RelA (therapeutic use)