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Pathogenesis of hypoxic-ischemic brain injury

Abstract

Accumulating evidence points to an evolving process of brain injury after intrapartum hypoxia-ischemia that initiates in utero and extends into a recovery period. The processes leading to cell death include necrosis or apoptosis, and result from the combined effects of cellular energy failure, acidosis, glutamate release, intracellular Ca2+ accumulation, generation of free radicals that serve to disrupt essential components of the cell. Many factors including the duration or severity of the insult influence the progression of cellular injury after hypoxia-ischemia. A secondary cerebral energy failure occurs from 6 to 48 h after the primary event and involves mitochondrial dysfunction secondary to extended reactions from primary insults (e.g., calcium influx, excitatory neurotoxicity and oxygen free radicals) as well as the release of circulatory and endogenous inflammatory cells/mediators that also contribute to ongoing brain injury. Strategies aimed at neuroprotection need to be comprehensive targeting the pathways leading to eventual mitochondrial injury.

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Perlman, J. Pathogenesis of hypoxic-ischemic brain injury. J Perinatol 27 (Suppl 1), S39–S46 (2007). https://doi.org/10.1038/sj.jp.7211716

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