Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep

Roelfsema, Vincent; Bennet, Laura; George, Sherly; Wu, David H.; Guan, Jian; Veerman, Marije; Gunn, Alistair J.

doi:10.1097/01.wcb.0000123904.17746.92

Cited by 112 publications

(92 citation statements)

References 64 publications

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“…Although mice have substantially less white matter as compared with human infants, we found a decrease in white matter injury after hypothermia, measured as loss of MBP and NF staining, and we also found that hypothermia decreased the loss of Olig-2-positive cells after HI. These data agree with previous publications showing that hypothermia protects white matter (27).…”

Section: Discussionsupporting

confidence: 93%

Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic–ischemic brain injury

et al. 2012

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Articles Translational Investigation nature publishing group INTODUCTION: hypoxia-ischemia (hI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (Ne), saving one in nine infants from developing neurological deficits. caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent hI brain damage. METHODS:The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of hI injury in mice. RESULTS: hI brain injury was moderately reduced in caspase-2 −/− mice as compared with wild-type (WT) mice. Five hours of hypothermia (33 °c ) vs. normothermia (36 °c) directly after hI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after hI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas. DISCUSSION: In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.

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Section: Discussionsupporting

confidence: 93%

Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic–ischemic brain injury

et al. 2012

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“…116 Similarly, hypothermia delays neutrophil accumulation and microglial activation following transient ischemia (Figure 4). 112,117 Thus, these data suggest that the hypothermic protection against post-ischemic neuronal damage might be, in part, due to suppression of microglial activation. Excitotoxity after hypoxia-ischemia.…”

Section: Suppression Of Apoptosis/ Programmed Cell Death?mentioning

confidence: 80%

Hypothermic neuroprotection

Gunn

Thoresen

2006

NeuroRX

214

128

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Summary:The possibility that hypothermia during or after resuscitation from asphyxia at birth, or cardiac arrest in adults, might reduce evolving damage has tantalized clinicians for a very long time. It is now known that severe hypoxia-ischemia may not necessarily cause immediate cell death, but can precipitate a complex biochemical cascade leading to the delayed neuronal loss. Clinically and experimentally, the key phases of injury include a latent phase after reperfusion, with initial recovery of cerebral energy metabolism but EEG suppression, followed by a secondary phase characterized by accumulation of cytotoxins, seizures, cytotoxic edema, and failure of cerebral oxidative metabolism starting 6 to 15 h post insult. Although many of the secondary processes can be injurious, they appear to be primarily epiphenomena of the 'execution' phase of cell death. Studies designed around this conceptual framework have shown that moderate cerebral hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration in relation to the severity of the cerebral injury, has been associated with potent, long-lasting neuroprotection in both adult and perinatal species. Two large controlled trials, one of head cooling with mild hypothermia, and one of moderate whole body cooling have demonstrated that post resuscitation cooling is generally safe in intensive care, and reduces death or disability at 18 months of age after neonatal encephalopathy. These studies, however, show that only a subset of babies seemed to benefit. The challenge for the future is to find ways of improving the effectiveness of treatment.

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“…Although there is no consensus on the exact treatment window for therapeutic hypothermia, it would be diicult to dispute the time-sensitive nature of hypothermia induction [31,40]. While one author found that TH is inefective after 45 min of ischemia [41] and most others have found neuroprotective eicacy when induction follows 2-3 h of ischemia [30,42], there is a strong consensus that this eicacy diminishes over the course of hours.…”

Section: Maximized Rate Of Coolingmentioning

confidence: 99%

Hypothermia in Stroke Therapy: Systemic versus Local Application

Huber¹,

Duan²,

Chandra³

et al. 2017

Hypoxia and Human Diseases

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Presently, there are no efective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective beneits of hypothermia, and surfacecooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and eicacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identiies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well.

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Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep

Cited by 112 publications

References 64 publications

Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic–ischemic brain injury

Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic–ischemic brain injury

Hypothermic neuroprotection

Hypothermia in Stroke Therapy: Systemic versus Local Application

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