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Review
. 2011;2011:609813.
doi: 10.1155/2011/609813. Epub 2010 Dec 13.

Perinatal Hypoxic-Ischemic Encephalopathy

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Free PMC article
Review

Perinatal Hypoxic-Ischemic Encephalopathy

Ming-Chi Lai et al. J Biomed Biotechnol. .
Free PMC article

Abstract

Perinatal hypoxic-ischemic encephalopathy (HIE) is an important cause of brain injury in the newborn and can result in long-term devastating consequences. Perinatal hypoxia is a vital cause of long-term neurologic complications varying from mild behavioural deficits to severe seizure, mental retardation, and/or cerebral palsy in the newborn. In the mammalian developing brain, ongoing research into pathophysiological mechanism of neuronal injury and therapeutic strategy after perinatal hypoxia is still limited. With the advent of promising therapy of hypothermia in HIE, this paper reviews the pathophysiology of HIE and the future potential neuroprotective strategies for clinical potential for hypoxia sufferers.

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Figure 1
Figure 1
Proposed pathogenesis of hypoxic-ischemic encephalopathy. The central roles for ATP depletion, membrane depolarization, glutamate-mediated excitotoxicty, and voltage-dependent and glutamate-activated Ca2+ channels are apparent. An initial decrease in high-energy phosphates can result in an acute influx of Na+, Cl, and water with consequent cell death (necrosis) in the severe insult, whereas in less severe insult, it causes membrane depolarization followed by a cascade of excitotoxicity and oxidative stress leading to a delayed cell death, principally apoptosis. Persistent membrane depolarization results excessive presynaptic glutamate release, reversal of glutamate transport in glia and neural terminals, and activation of NMDA and immature (GluR2 deficiency) AMPA receptors with profound Ca2+ influx with a series of Ca2+-mediated cascades to cell death. The deleterious effects of cytosolic Ca2+ are multiple, including degradation of cellular lipids by activation of phospholipase and of cellular DNA by activation of nucleases and enhancement of generation of free radicals and nitric oxide (NO) by increase of nitric oxide synthase (NOS) [7, 8, 26]. AMPA: α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate; ER: endoplasmic reticulum; mGlu: metabotropic glutamate; NMDA: N-methyl-D-aspartic acid; NOS: nitric oxide synthase; VDCC: voltage-dependent calcium channels

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