Journal of Neuroimmune Pharmacology

, Volume 8, Issue 1, pp 66–78 | Cite as

Roles of Activated Microglia in Hypoxia Induced Neuroinflammation in the Developing Brain and the Retina

INVITED REVIEW

Abstract

Amoeboid microglial cells (AMCs) in the developing brain display surface receptors and antigens shared by the monocyte-derived tissue macrophages. Activation of AMCs in the perinatal brain has been associated with periventricular white matter damage in hypoxic-ischemic conditions. The periventricular white matter, where the AMCs preponderate, is selectively vulnerable to hypoxia as manifested by death of premyelinating oligodendrocytes and degeneration of axons leading to neonatal mortality and long-term neurodevelopmental deficits. AMCs respond vigorously to hypoxia by producing excess amounts of inflammatory cytokines e.g. the tumor necrosis factor–α (TNF-α) and interleukin-1β (IL-1β) along with glutamate, nitric oxide (NO) and reactive oxygen species which collectively cause oligodendrocyte death, axonal degeneration as well as disruption of the immature blood brain barrier. A similar phenomenon is observed in the hypoxic developing cerebellum in which activated AMCs induced Purkinje neuronal death through production of TNF-α and IL-1β via their respective receptors. Hypoxia is also implicated in retinopathy of prematurity in which activation of AMCs has been shown to cause retinal ganglion cell death through production of TNF-α and IL-1β and NO. Because AMCs play a pivotal role in hypoxic injuries in the developing brain affecting both neurons and oligodendrocytes, a fuller understanding of the underlying molecular mechanisms of microglial activation under such conditions would be desirable for designing of a novel therapeutic strategy for management of hypoxic damage.

Keywords

Amoeboid microglia Hypoxia Developing brain Retina Oligodendrocyte/neuronal damage Inflammatory cytokines Reactive oxygen species 

Abbreviation

AMCs

Amoeboid microglial cells

AMPA

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

CNS

Central nervous system

CR3

Complement type 3 receptors

CSF-1

Colony stimulating factor

GluR2-4

AMPA glutamate receptors

IGF-1

Insulin-like growth factor-1

IGF-2

Insulin-like growth factor-2

IL-1 β

Interleukin-1β

IL-1R

Interleukin 1 receptor

iNOS

Nitric oxide synthase

MBP

Myelin basic protein

MCP-1

Monocyte chemoattractant protein-1

M-CSF

Macrophage-colony stimulating factor

MHC I

Major histocompatibility class I antigens

MHC II

Major histocompatibility class II antigens

NMDA

N-methyl-D-aspartate

NR1, NR2A-D

NMDA receptor subunits

NO

Nitric oxide

PWM

Periventricular white matter

PWMD

Periventricular white matter damage

RGC

Retinal ganglion cell

RGCs

Retinal ganglion cells

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

TβRI and TβRII

Transforming growth factor receptors I and II

TGF-βl

Transforming growth factor βl

TNF-α

Tumor necrosis factor –α

TNF-R1, TNF-R2

TNF receptor 1 or 2

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Anatomy, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

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