Hypothermia to Treat Neonatal Hypoxic Ischemic Encephalopathy

Shah, Prakesh S.; Ohlsson, Arne; Perlman, Max

doi:10.1001/archpedi.161.10.951

Cited by 166 publications

(40 citation statements)

References 43 publications

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“…[91] reported a meta-analysis of the large randomized controlled cooling trials, with the primary outcome of death or impairment in childhood [83, 92–94] (Table 2). This meta-analysis of 249 cooled infants and 248 control infants showed significant reduction in the risk of death or moderate to severe neurodevelopmental disability in infants who received hypothermia compared with control infants, with a relative risk (RR) of 0.76, and a 95% confidence interval (CI) of 0.65–0.88.…”

Section: Clinical Implications Of Hypothermiamentioning

confidence: 99%

Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

Sinha²,

Pandya³

et al. 2012

CMM

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Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury.

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Section: Clinical Implications Of Hypothermiamentioning

confidence: 99%

Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

Sinha²,

Pandya³

et al. 2012

CMM

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“…7,22 In general, cardiovascular changes during hypothermia therapy seem to be well tolerated in neonates, with no evidence of significant compromise to organ perfusion. 10,23 …”

Section: Physiologic Effects Of Hypothermiamentioning

confidence: 99%

Physiologic and pharmacologic considerations for hypothermia therapy in neonates

2010

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With mounting evidence that hypothermia is neuroprotective in newborns with hypoxic-ischemic encephalopathy (HIE), an increasing number of centers are offering this therapy. Hypothermia is associated with a wide range of physiologic changes affecting every organ system, and awareness of these effects is essential for optimum patient management. Lowering the core temperature also alters pharmacokinetic and pharmacodynamic properties of medications commonly used in asphyxiated neonates, necessitating close attention to drug efficacy and side effects. Rewarming introduces additional risks and challenges as the hypothermia-associated physiologic and pharmacologic changes are reversed. In this review we provide an organ system-based assessment of physiologic changes associated with hypothermia. We also summarize evidence from randomized controlled trials showing lack of serious adverse effects of moderate hypothermia therapy in term and near-term newborns with moderate-to-severe HIE. Finally, we review the effects of hypothermia on drug metabolism and clearance based on studies in animal models and human adults, and limited data from neonates.

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“…These deficits occur because the developing forebrain is very sensitive to hypoxic-ischemic injury (HI) [5]. Treatment options for neonatal HI are extremely limited, and hypothermia is the only widely used and well-validated therapy that is effective in reducing rates of permanent neurocognitive disability [6,7,8]. Since the fundamental pathophysiology of neonatal HI involves massive neuronal death [9], one promising pathway to substantial recovery is through repopulation of lost cells by enhancement of neural stem cell activity.…”

Section: Introductionmentioning

confidence: 99%

Effects of Neonatal Hypoxic-Ischemic Injury and Hypothermic Neuroprotection on Neural Progenitor Cells in the Mouse Hippocampus

Kwak¹,

Lim²,

Kang

et al. 2015

Dev Neurosci

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Neonatal hypoxic-ischemic injury (HI) results in widespread cerebral encephalopathy and affects structures that are essential for neurocognitive function, such as the hippocampus. The dentate gyrus contains a reservoir of neural stem and progenitor cells (NSPCs) that are critical for postnatal development and normal adult function of the hippocampus, and may also facilitate the recovery of function after injury. Using a neonatal mouse model of mild-to-moderate HI and immunohistochemical analysis of NSPC development markers, we asked whether these cells are vulnerable to HI and how they respond to both injury and hypothermic therapy. We found that cleaved caspase-3 labeling in the subgranular zone, where NSPCs are located, is increased by more than 30-fold after HI. The population of cells positive for both proliferating cell nuclear antigen and nestin (PCNA+Nes+), which represent primarily actively proliferating NSPCs, are acutely decreased by 68% after HI. The NSPC population expressing NeuroD1, a marker for NSPCs transitioning to become fate-committed neural progenitors, was decreased by 47%. One week after HI, there was a decrease in neuroblasts and immature neurons in the dentate gyrus, as measured by doublecortin (DCX) immunolabeling, and at the same time PCNA+Nes+ cell density was increased by 71%. NSPCs expressing Tbr2, which identifies a highly proliferative intermediate neural progenitor population, increased by 107%. Hypothermia treatment after HI partially rescues both the acute decrease in PCNA+Nes+ cell density at 1 day after injury and the chronic loss of DCX immunoreactivity and reduction in NeuroD1 cell density measured at 1 week after injury. Thus, we conclude that HI causes an acute loss of dentate gyrus NSPCs, and that hypothermia partially protects NSPCs from HI.

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Hypothermia to Treat Neonatal Hypoxic Ischemic Encephalopathy

Abstract: In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.

Cited by 166 publications

References 43 publications

Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

Physiologic and pharmacologic considerations for hypothermia therapy in neonates

Effects of Neonatal Hypoxic-Ischemic Injury and Hypothermic Neuroprotection on Neural Progenitor Cells in the Mouse Hippocampus

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