Multiple Roles of Peripheral Immune System in Modulating Ischemia/Hypoxia-Induced Neuroinflammation.

Liang Guo,Lingling Zhu

doi:10.3389/fmolb.2021.752465

Abstract

Given combined efforts of neuroscience and immunology, increasing evidence has revealed the critical roles of the immune system in regulating homeostasis and disorders of the central nervous system (CNS). Microglia have long been considered as the only immune cell type in parenchyma, while at the interface between CNS and the peripheral (meninges, choroid plexus, and perivascular space), embryonically originated border-associated macrophages (BAMs) and multiple surveilling leukocytes capable of migrating into and out of the brain have been identified to function in the healthy brain. Hypoxia-induced neuroinflammation is the key pathological procedure that can be detected in healthy people at high altitude or in various neurodegenerative diseases, during which a very thin line between a beneficial response of the peripheral immune system in maintaining brain homeostasis and a pathological role in exacerbating neuroinflammation has been revealed. Here, we are going to focus on the role of the peripheral immune system and its crosstalk with CNS in the healthy brain and especially in hypobaric or ischemic hypoxia-associated neuroinflammation.

Highlights

The proper function of central nervous system (CNS) is protected by the immune system, including the CNS-resident and the peripheral immunity
We found that preexisting systemic inflammation rapidly induced the onset of brain edema upon 6 h of acute hypobaric hypoxia (AHH) exposure by disrupting blood-brain barrier (BBB) integrity, activating microglia, and increasing water permeability via AQP4, which elicited impaired cognitive and motor function in mouse models, whereas AHH exposure without LPS-induced systemic inflammation could only induce a slight brain edema within 24 h (Zhou et al, 2017)
Peripheral immune plays critical roles in both steady-state brain and cerebral disorders induced by hypoxia

Summary

Introduction

The proper function of central nervous system (CNS) is protected by the immune system, including the CNS-resident and the peripheral immunity. A bidirectional crosstalk between the peripheral and CNS immunity in response to hypoxia has been revealed and multiple cell types have been suggested to exert differential roles in the generation and progression of hypoxic brain injuries (Li et al, 2017).

Results

Conclusion