[Frontiers in Bioscience S3, 884-900, June 1, 2011]

Role of microglia in the process of inflammation in the hypoxic developing brain

Yi Yu Deng 1, Jia Lu2, Eng-Ang Ling1, Charanjit Kaur1 

1Department of Anatomy, Yong Loo Lin School of Medicine, Blk MD10, 4 Medical Drive, National University of Singapore, Singapore 117597,  2Defence Medical and Environmental Research Institute, DSO National Laboratories,27 Medical drive, Singapore 117510

TABLE CONTENTS

1. Abstract
2. Introduction
3. Etiology and risk factors of hypoxic brain injury
4. Pathological changes of the hypoxic developing brain
4.1. Neuronal loss
4.2. Oligodendrocyte injury and myelination delay
4.3. Axon injury
4.4. Microglia activation and astrogliosis
4.5. Blood-Brain Barrier damage
5. Inflammation in the hypoxic developing brain
6. Roles of microglia in the neuroinflammatory response in the hypoxic developing brain
6.1. Distribution and morphology of microglia
6.2. Phagocytosis
6.3. Antigen presentation
6.4. Proliferation
6.5. Migration
6.6. Release of cytokines and chemokines
6.6.1. Tumor necrosis factor-α and its receptors
6.6.2. Interleukin-1 and its receptors
6.6.3. Macrophage colony stimulating factor
6.6.4. Monocyte chemoattractant protein-1
6.7. Expression of ion channels
6.7.1. Kv1.2 .and Kv1.1 .
6.7.2. Sodium channels
6.8. Syndecan-2
6.9. Generation of reactive oxygen species and nitrogen intermediates
7. Conclusions
8. Acknowledgements
9. References

1. ABSTRACT

The developing brain is susceptible to hypoxic damage because of its high oxygen and energy requirements. Hypoxia-induced inflammatory response has been recognized as one of the main culprits in the development of hypoxic brain injury. In this regard, a hallmark feature is microglial activation which results in overproduction of inflammatory cytokines, free radicals and nitric oxide. Concomitantly, activated microglia exhibit enhanced expression of ion channels such as Kv1.2, Kv1.1 and Nav which further promote the release of inflammatory cytokines, chemokines and reactive oxygen species. Through the above-mentioned inflammatory mediators, activated microglia induce neuronal loss, axonal damage and oligodendroglial death along with myelination disturbances. Our recent studies have extended that tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1 and macrophage colony stimulating factor produced by activated microglia are linked to the pathogenesis of periventricular white matter damage in the hypoxic brain. It is envisaged that a better understanding of the interactions between microglia and neurons, axons and oligodendrocytes is key to the development of effective preventive and therapeutic strategies for mitigation of hypoxic brain injury.