Exposure to Cigarette Smoke Augments Post-ischemic Brain Injury and Inflammation via Mobilization of Neutrophils and Monocytes.

Handong Li,Hongshan Ma,Siman Gao,Zhigang Cui,Qiang Liu,Xiaolin Gao,Minshu Li,Dan Wang,Xiuping Li,Xuejiao Wang,Yujing Li

doi:10.3389/fimmu.2019.02576

Abstract

Cigarette smoke is a major preventable risk factor of ischemic stroke. Cigarette smoke induces a significant increase in circulating leukocytes. However, it remains unclear to what extent and by what mechanisms smoke priming influences stroke severity. Here we report that exposure to cigarette smoke exacerbated ischemic brain injury in mice subjected to transient middle cerebral artery occlusion (MCAO). The augmentation of neurodeficits and brain infarction was accompanied by increased production of pro-inflammatory factors and brain infiltration of neutrophils and monocytes. Prior to brain ischemia, exposure to cigarette smoke induced mobilization of peripheral neutrophils, and monocytes. Furthermore, the detrimental effects of smoke priming on ischemic brain injury were abolished either by pharmacological inhibition of the recruitment of neutrophils and monocytes or by blockade of the NLRP3 inflammasome, an effector protein of neutrophils and monocytes. Our findings suggest that cigarette smoke-induced mobilization of peripheral neutrophils and monocytes augments ischemic brain injury.

Highlights

Despite progresses in reperfusion therapies, ischemic stroke remains a major cause of death and disability worldwide
We investigated the effects of cigarette smoke on post-ischemic brain injury and inflammation, and we determined the contributions of cigarette smoke-induced priming of peripheral immune cells to the effects of cigarette smoke in mice subjected to transient middle cerebral artery occlusion (MCAO)
To assess the impact of cigarette smoke on ischemic brain injury, we measured neurodeficits and infarct volume in mice subjected to exposure of cigarette smoke followed by brain ischemia induced by 60 min transient MCAO

Summary

Introduction

Despite progresses in reperfusion therapies, ischemic stroke remains a major cause of death and disability worldwide. Compiling evidence has demonstrated that inflammatory responses to cerebral ischemia plays an important role in various stages of stroke pathobiology and outcome. Initiated by the cessation of blood flow, the activation of neuroglia, recruitment of peripheral leukocytes, and release of proinflammatory factors from the ischemic region together contribute to post-ischemic brain injury [1, 2]. Tobacco use is a major preventable risk factor for ischemic stroke. Smokers have a two- to four-fold increased risk of stroke than non-smokers [3]. Cigarette smoking has a strong link to stroke severity, disability, and length of inpatient stay [4]. A significant increase in circulating leukocytes, such as neutrophils and monocytes, and pro-inflammatory factors, such as Cigarette Smoking Exacerbates Brain Infarction

Methods

Results

Conclusion