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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxic-ischemic brain injury in the perinatal period is a major cause of morbidity and mortality. Presently, there are no proven effective therapies with which to safeguard the human neonatal brain against this type of injury. Minocycline, a semisynthetic tetracycline, has been shown to be neuroprotective in certain adult ischemic injury/stroke and neurodegenerative disease models. However, minocycline's neuroprotective effects have not been assessed after insults to the neonatal brain. We now report that minocycline administered either immediately before or immediately after a hypoxic-ischemic insult substantially blocks tissue damage in a rodent model of neonatal hypoxic-ischemic brain injury. Minocycline treatment prevents the formation of activated caspase-3, a known effector of apoptosis, as well as the appearance of a calpain cleaved substrate, a marker of excitotoxic/necrotic cell death. To our knowledge, this is the first report of a systemic treatment that can be administered after a hypoxic-ischemic insult, which provides robust, nearly complete neuroprotection to the developing brain. Our data suggest that minocycline or a related neuroprotective tetracycline may be a candidate to consider in human clinical trials to protect the developing brain against hypoxic-ischemic-induced damage.
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PMID:Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. 1211 47

Hypoxic-ischemic brain injury in the perinatal period is a major cause of chronic disability and acute mortality in newborns. Despite numerous therapeutic strategies that reduce hypoxia-ischemia-induced damage in different experimental animal models, most of them have failed to translate to clinical therapies. This challenge calls for an urgent need to explore novel approaches to develop effective therapies for the clinical management of perinatal hypoxia-ischemia brain injury. This review focuses on studies that investigate neuroprotective related events during mammalian hibernation, characterized by dramatic reductions in several parameters including body temperature, oxygen consumption and heart rate, such that it is difficult to tell if the hibernating animal is dead or alive. The first part of this article reviews the mechanisms of metabolic suppression related events during hibernation. In the second part, hypoxic-ischemic events in the perinatal brain are discussed, and in turn, contrasted with brains experiencing metabolic suppression during mammalian hibernation. In the last part of this article, the diverse neuroprotective adaptations of hibernators and the mechanisms that might be involved in mammalian hibernation, and how they could in turn, contribute to neurprotection during perinatal hypoxia-ischemia related injuries are discussed. This article appraises the novel idea that knowledge of the central mechanisms involved in the regulatory metabolic suppression, during which; hibernators switch themselves off without dissolving their brains could represent brain neuroprotective strategy for the clinical management of perinatal hypoxia-ischemia brain injuries in newborns.
Int J Stroke 2008 May
PMID:Brain-regulated metabolic suppression during hibernation: a neuroprotective mechanism for perinatal hypoxia-ischemia. 1870 3

Hypoxic-ischemic brain injury is an important cause of neonatal mortality and subsequent serious neurological sequel. In neonatal brain the severity of hypoxic injury varies most probably due to the effects of multiple protective or deleterious factors. But the mechanisms under this difference are still not full understood. In recent years, some evidence has been found supporting the involvement of epigenetic mechanisms in many neurodegenerative diseases and stroke. We hypothesised that epigenetic mechanisms have been also involved in neonatal hypoxic-ischemic brain injury possibly by suppression of ischemia-induced cerebral inflammation and changing the expression of proapoptotic-antiapoptotic genes.
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PMID:Role of epigenetic regulatory mechanisms in neonatal hypoxic-ischemic brain injury. 1926 50

Hypoxic-ischemic brain injury and stroke are closely related and devastating conditions that can affect individuals of all ages.[...].
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PMID:Pathophysiology and Neuroprotective Strategies in Hypoxic-Ischemic Brain Injury and Stroke. 2882 50

Hypoxic-ischemic brain injury is a significant cause of morbidity and mortality in the adult as well as in the neonate. Extensive pre-clinical studies have shown promising therapeutic effects of neural stem cell-based treatments for hypoxic-ischemic brain injury. There are two major strategies of neural stem cell-based therapies: transplanting exogenous neural stem cells and boosting self-repair of endogenous neural stem cells. Neural stem cell transplantation has been proved to improve functional recovery after brain injury through multiple by-stander mechanisms (e.g., neuroprotection, immunomodulation), rather than simple cell-replacement. Endogenous neural stem cells reside in certain neurogenic niches of the brain and response to brain injury. Many molecules (e.g., neurotrophic factors) can stimulate or enhance proliferation and differentiation of endogenous neural stem cells after injury. In this review, we first present an overview of neural stem cells during normal brain development and the effect of hypoxic-ischemic injury on the activation and function of endogenous neural stem cells in the brain. We then summarize and discuss the current knowledge of strategies and mechanisms for neural stem cell-based therapies on brain hypoxic-ischemic injury, including neonatal hypoxic-ischemic brain injury and adult ischemic stroke.
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PMID:Neural stem cell therapies and hypoxic-ischemic brain injury. 2975 44

Hypoxic-ischemic brain injury is a complex network of factors, which is mainly characterized by a decrease in levels of oxygen concentration and blood flow, which lead to an inefficient supply of nutrients to the brain. Hypoxic-ischemic brain injury can be found in perinatal asphyxia and ischemic-stroke, which represent one of the main causes of mortality and morbidity in children and adults worldwide. Therefore, knowledge of underlying mechanisms triggering these insults may help establish neuroprotective treatments. Selective Estrogen Receptor Modulators and Selective Tissue Estrogenic Activity Regulators exert several neuroprotective effects, including a decrease of reactive oxygen species, maintenance of cell viability, mitochondrial survival, among others. However, these strategies represent a traditional approach of targeting a single factor of pathology without satisfactory results. Hence, combined therapies, such as the administration of therapeutic hypothermia with a complementary neuroprotective agent, constitute a promising alternative. In this sense, the present review summarizes the underlying mechanisms of hypoxic-ischemic brain injury and compiles several neuroprotective strategies, including Selective Estrogen Receptor Modulators and Selective Tissue Estrogenic Activity Regulators, which represent putative agents for combined therapies with therapeutic hypothermia.
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PMID:Neuroprotective Role of Hypothermia in Hypoxic-ischemic Brain Injury: Combined Therapies using Estrogen. 3052 Mar 75