Pathogenesis of hypoxic-ischemic brain injury

Perlman, Jeffrey M.

doi:10.1038/sj.jp.7211716

Cited by 41 publications

(37 citation statements)

References 87 publications

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“…These cascades include reoxygenation-induced oxidative stress, activation of immune cells and their release of inflammatory mediators and mitochondrial dysfunction that results in the activation of apoptotic pathways [4][5][6][7][8]. The oxygen radicals not only damage cellular lipids, proteins and nucleic acids, but also initiate cell signaling pathways that play key roles in mediating distinct cellular responses, including glial cell activation and neuronal apoptosis, following hypoxia-ischemia (HI) [6].…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia (H) and HI are also the most common causes of perinatal brain damage resulting in long-lasting clinical and behavioral problems [2][3][4]. Several mechanisms have been proposed for HI-induced neuronal injury including excitotoxicity, oxidative stress and apoptosis [5][6][7]. In addition, there may be immunological changes with increased production of cytotoxic inflammatory mediators [4,8] potentially contributing to neuronal and glial injury.…”

Section: Introductionmentioning

confidence: 99%

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p38α MAP Kinase Mediates Hypoxia-Induced Motor Neuron Cell Death: A Potential Target of Minocycline’s Neuroprotective Action

Guo

Bhat

2007

Neurochem Res

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Hypoxia-ischemia (HI) may play a significant role in motor neuron death associated with the pathology of spinal cord injury and, perhaps, amyotrophic lateral sclerosis. The present study employs an in vitro model of HI to investigate the role of a stress kinase pathway, i.e., p38 MAP kinase, in cell death signaling in a motor neuron cell line, i.e., NSC34, subjected to oxygen-glucose deprivation (OGD). Although the neurons were essentially tolerant to either hypoxia (0.2% O(2)) or low glucose (1 mM) alone, more than 60% of them died in response to combined low oxygen and low-glucose exposure. Minocycline, a semi-synthetic tetracycline known for its neuroprotective effects in models of neurodegeneration, afforded substantial (approximately 50%) protection against hypoxic cell death, assessed by lactate dehydrogenase release and flow cytometry, while suppressing OGD-induced p38 MAP kinase activation. An inhibitor of p38 kinase, SB203580, as well as siRNA-mediated down-regulation of p38 kinase elicited an almost complete blockade of OGD-induced cell death. The use of p38 isoform-specific siRNAs further revealed preferential involvement of the alpha over the beta isoform of p38 MAP kinase in hypoxic neuronal cell death in our model.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

p38α MAP Kinase Mediates Hypoxia-Induced Motor Neuron Cell Death: A Potential Target of Minocycline’s Neuroprotective Action

Guo

Bhat

2007

Neurochem Res

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“…Ischemia leads to a reduction of up to 80% in cerebral blood flow in “core” tissue, leading to a disruption of delivery of glucose and oxygen to cells for ATP generation [51–52•]. The mechanisms of neuronal cell death in animals and humans after H/I can be categorized into two major phases, neuronal necrosis during acute insult, and neuronal apoptosis during a recovery period following circulatory restoration, often termed reperfusion injury [51, 53].…”

Section: Mechanisms Of Neuronal Cell Death Following Hypoxia-ischemiamentioning

confidence: 99%

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia

Mayurasakorn¹,

Williams²,

Ten³

et al. 2011

Current Opinion in Clinical Nutrition and Metabolic Care

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Purpose of review With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. Recent findings DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between pre-and post-synaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing anti-apoptotic activities such as decreasing responses to reactive oxygen species, up-regulating anti-apoptotic protein expression, down-regulating apoptotic protein expression, and maintaining mitochondrial integrity and function. Summary DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression.

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“…Many studies have focused on the short-term cardiovascular and neurological consequences of neonatal hypoxia ( [2][3][4][5][6] ). We have extensively characterized the short-term endocrine and metabolic effects of hypoxia from birth to 7 d of age.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Raff

Bruder

2006

ENDO

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Hypoxia is a common neonatal stress that induces insulin resistance and a decrease in body weight gain. Dexamethasone is often used to treat neonatal cardiopulmonary disease, and also leads to insulin resistance and a decrease in body weight gain. The current study addressed the hypothesis that serum concentrations of the adipokines adiponectin and/or resistin are altered during hypoxia and/or dexamethasone therapy in neonatal rats. Rat pups with their lactating dams were exposed to hypoxia (11% O 2 ) from birth and treated with a tapering regimen of dexamethasone from postnatal day (PD) 3-6. Serum adiponectin and resistin were measured on PD7. Hypoxia and dexamethasone independently decreased body weight gain and increased adiponectin levels. The combination of hypoxia and dexamethasone did not further increase adiponectin. Dexamethasone caused a small increase in resistin in normoxic pups, which may facilitate the hyperinsulemic-normoglycemic state we previously described. We also conclude that adiponectin is increased during hypoxia in response to a decrease in the sensitivity to insulin.

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Pathogenesis of hypoxic-ischemic brain injury

Cited by 41 publications

References 87 publications

p38α MAP Kinase Mediates Hypoxia-Induced Motor Neuron Cell Death: A Potential Target of Minocycline’s Neuroprotective Action

p38α MAP Kinase Mediates Hypoxia-Induced Motor Neuron Cell Death: A Potential Target of Minocycline’s Neuroprotective Action

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia

Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

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