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

  • Charanjit KaurEmail author
  • Gurugirijha Rathnasamy
  • Eng-Ang LingEmail author


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.


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



Amoeboid microglial cells


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


Central nervous system


Complement type 3 receptors


Colony stimulating factor


AMPA glutamate receptors


Insulin-like growth factor-1


Insulin-like growth factor-2

IL-1 β



Interleukin 1 receptor


Nitric oxide synthase


Myelin basic protein


Monocyte chemoattractant protein-1


Macrophage-colony stimulating factor


Major histocompatibility class I antigens


Major histocompatibility class II antigens




NMDA receptor subunits


Nitric oxide


Periventricular white matter


Periventricular white matter damage


Retinal ganglion cell


Retinal ganglion cells


Reactive nitrogen species


Reactive oxygen species

TβRI and TβRII

Transforming growth factor receptors I and II


Transforming growth factor βl


Tumor necrosis factor –α


TNF receptor 1 or 2



This study was supported by a research grant (R181-000-120-213) from National Medical Research Council of Singapore. We thank Dr. Viswanathan Sivakumar for providing the technical assistance. There is no conflict of interest among the authors.


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© 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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