Perinatal Cerebral Asphyxia: Pharmacological Intervention

Gunn, Alistair J.; Williams, Christopher E.; Cook, C. J.; Gluckman, Peter D.

doi:10.1159/000263339

Cited by 6 publications

(1 citation statement)

References 39 publications

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“…Several studies have demonstrated the beneficial effects of antagonists directed towards glutamate receptors. For instance, pretreatment with the N MDA‐receptor antagonist MK801 in the rat 89–91 , and in catheterised fetal sheep 92 affords marked neuroprotection. In P7 rats subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (7.7% oxygen), treatment with the N MDA antagonist kyneuronic acid resulted in the volume of cerebral infarction being reduced by one‐ third (from 38 to 25%) 93 .…”

Section: Prominent Hypothesesmentioning

confidence: 99%

Hypoxia‐ischaemia and the developing brain: hypotheses regarding the pathophysiology of fetal–neonatal brain damage

Longo¹,

Packianathan²

1997

BJOG

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REVIEW Hypoxia-ischaemia and the developing brain: hypotheses regarding the pathophysiology of fetal-neonatal brain damage IntroductionDespite striking advances in obstetrical and neonatal care, encephalopathy induced by hypoxia-ischaemia of the fetus and newborn infant continues to be an important problem in society. Because one of the tasks of the obstetrician is the prevention of any condition which could jeopardise the proper functioning and viability of the fetus and its brain, considerable attention has been devoted to describing the neuropathologic sequelae, and to detecting and preventing of hypoxia-asphyxiaischaemia during the perinatal period. Both clinical studies and experiments in laboratory animals have described the physiologic as well as the abnormal fetal and newborn cardiovascular and respiratory responses. Contemporary techniques, such as nuclear magnetic resonance spectroscopy and positron emission tomography, have provided information demonstrating the relevance of lessons learned in the laboratory to humans. Despite major advances, however, it is only recently that attempts have been made to understand the underlying cellular and molecular events associated with brain damage in the fetus and newborn infant induced by hypoxia-ischaemia. Several previous reviews have described the events which lead to cell death induced by hypoxiaischaemia'". The purpose of the present review is to consider the several hypotheses regarding this condition, to examine supporting data and their inadequacies, and to put these competing concepts in perspective.Although as yet we do not understand much of the pathophysiology of brain damage caused by hypoxiaischaemia in the fetus and newborn infant, less still how to prevent or treat it, we believe that the best probability of success in such an endeavor lies in a continued emphasis on elucidating and understanding the molecular reactionshearrangements that occur in the cell in response to this insult. It is our premise that a deeper understanding of the cellular and subcellular basis of hypoxia-ischaemia and its neurological sequelae will lead to development of improved diagnostic and predictive modalities. In addition, advances in these areas may provide a rational basis for the development of selective 652 and efficacious interventions to prevent or minimise brain damage. DefinitionsPerhaps several definitions are in order at this point. Generally, hypoxia refers to a relative lack of oxygen (e.g. low oxygen content or tension) in the ambient air or tissues. Strictly speaking, hypoxia, or 'dysoxia', means oxygen-limited energy flux and electron transfer in the mitochondria1 cytochrome oxidase system, rather than low oxygen content or tension, per se'. Hypoxaemia refers to deficient oxygenation of arterial blood. Although an imprecise term, asphyxia is synonymous with suffocation (i.e. hypoxia combined with increased carbon dioxide tension and decreased pH). Ischaemia is insufficiency of blood flow to a given organ or tissue. Historical antecedentsIn 1843 and 184...

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Section: Prominent Hypothesesmentioning

confidence: 99%

Hypoxia‐ischaemia and the developing brain: hypotheses regarding the pathophysiology of fetal–neonatal brain damage

Longo¹,

Packianathan²

1997

BJOG

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Cerebral Palsy: Treatments and Therapeutics

Ferguson

2015

Encyclopedia of Life Sciences

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Cerebral palsy ( CP ) is a non‐progressive motor disorder affecting approximately 3 out of every 1000 infants in the United States. Although it is classified as a motor disorder, the deficits are caused by pre‐ or neonatal brain injury. Unfortunately, there is no cure for CP and currently, symptom management is the only treatment option available. As research begins to unravel the underlying causes and cellular changes leading to CP , potential treatments and therapeutics can be investigated to prevent brain damage following insults. Today, only two therapies are approved for use in the hospital setting: hypothermia and magnesium sulphate. Both of these therapies attempt to lessen the brain damage by slowing processes of inflammation and cell death. Other potential therapies are in clinical trials to test safety and efficacy for use in humans. Some drugs have shown promise in animal models; however, they have not yet been tested in humans. Researchers are searching for a cure. Key Concepts There is no cure for cerebral palsy and currently approved treatments target the symptoms of cerebral palsy, not the underlying causes. Hypothermia and magnesium sulphate are the only two therapeutics used in the hospital setting to slow or lessen brain damage following labour and delivery complications. Therapeutics targeting the excitatory amino acid neurotransmitter glutamate, along with glutamate receptor and transporter expression and function, appear to be promising. Drug treatments targeting growth factors and endogenous proteins may be beneficial to reduce cell death leading to cerebral palsy. Because inflammation plays a role in cerebral palsy, drug treatment that reduces the inflammatory response may also reduce brain damage following insults.

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Long-lasting changes in hippocampal synaptic plasticity and cognition in an animal model of NMDA receptor dysfunction in psychosis

Wiescholleck

Manahan‐Vaughan

2013

Neuropharmacology

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Perinatal Cerebral Asphyxia: Pharmacological Intervention

Cited by 6 publications

References 39 publications

Hypoxia‐ischaemia and the developing brain: hypotheses regarding the pathophysiology of fetal–neonatal brain damage

Hypoxia‐ischaemia and the developing brain: hypotheses regarding the pathophysiology of fetal–neonatal brain damage

Cerebral Palsy: Treatments and Therapeutics

Long-lasting changes in hippocampal synaptic plasticity and cognition in an animal model of NMDA receptor dysfunction in psychosis

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