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3 - Cellular and molecular biology of hypoxic–ischemic encephalopathy

from Section 1 - Epidemiology, pathophysiology, and pathogenesis of fetal and neonatal brain injury

Published online by Cambridge University Press:  12 January 2010

By
Zinaida S. Vexler ,
Donna M. Ferriero  and
Janet Shimotake
Edited by
David K. Stevenson ,
William E. Benitz ,
Philip Sunshine ,
Susan R. Hintz  and
Maurice L. Druzin
David K. Stevenson
Affiliation:
Stanford University School of Medicine, California
William E. Benitz
Affiliation:
Stanford University School of Medicine, California
Philip Sunshine
Affiliation:
Stanford University School of Medicine, California
Susan R. Hintz
Affiliation:
Stanford University School of Medicine, California
Maurice L. Druzin
Affiliation:
Stanford University School of Medicine, California
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Summary

Introduction

The exact timing of hypoxic–ischemic brain injury and the preceding course of events are often unknown, but they play a crucial role in pathogenesis, regional susceptibility, and injury severity in humans, requiring different treatment approaches. The dynamic nature of the developing brain requires the use of age-appropriate models to advance our understanding of both the injurious mechanisms and the means to ameliorate injury.

Several aspects of injury to the immature brain caused by experimental hypoxia–ischemia (HI) or focal stroke in animals have been recently reviewed, including the role of age, blood-flow regulation and energy metabolism, inflammation, intracellular injury mechanisms, and neuronal death, and these will not be covered in great detail here. We will review recently emerging concepts, including the status of the neurovascular unit and blood–brain barrier, neuroinflammation, adaptive intracellular mechanisms, gender differences in the injury response, neuroprotection, and brain repair.

Energy failure and early intracellular injury

The role of disruption of cerebral blood flow and failure of mitochondrial ATP production in initiating injury after HI has been recently reviewed by Vannucci & Vannucci and Perlman. The role of elevated levels of extracellular glutamate, overactivation of excitatory amino acid (EAA) receptors, and calcium (Ca2+i)-mediated intracellular injury, which in part depends on failure of ATP-dependent processes, have been recently reviewed as well.

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Fetal and Neonatal Brain Injury , pp. 38 - 47
Publisher: Cambridge University Press
Print publication year: 2009

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