Cooling and immunomodulation for treating hypoxic‐ischemic brain injury

Cho, Kenta H T; Davidson, John B.; Dean, Justin M.; Gunn, Alistair J.

doi:10.1111/ped.14215

Cited by 20 publications

(13 citation statements)

References 86 publications

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“…These investigators found encouraging results of stem cell therapy in small animals, suggesting augmented hypothermic neuroprotection. However, still the evidence of these effects are conflicting and the authors recommend rigorous testing in translational animal models ( 165 ).…”

Section: Hypothermia-induced Changes In Organ Functionsmentioning

confidence: 99%

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update

et al. 2022

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BackgroundAccidental hypothermia (AH) is an unintended decrease in body core temperature (BCT) to below 35°C. We present an update on physiological/pathophysiological changes associated with AH and rewarming from hypothermic cardiac arrest (HCA).Temperature Regulation and MetabolismTriggered by falling skin temperature, Thyrotropin-Releasing Hormone (TRH) from hypothalamus induces release of Thyroid-Stimulating Hormone (TSH) and Prolactin from pituitary gland anterior lobe that stimulate thyroid generation of triiodothyronine and thyroxine (T4). The latter act together with noradrenaline to induce heat production by binding to adrenergic β3-receptors in fat cells. Exposed to cold, noradrenaline prompts degradation of triglycerides from brown adipose tissue (BAT) into free fatty acids that uncouple metabolism to heat production, rather than generating adenosine triphosphate. If BAT is lacking, AH occurs more readily.Cardiac OutputAssuming a 7% drop in metabolism per °C, a BCT decrease of 10°C can reduce metabolism by 70% paralleled by a corresponding decline in CO. Consequently, it is possible to maintain adequate oxygen delivery provided correctly performed cardiopulmonary resuscitation (CPR), which might result in approximately 30% of CO generated at normal BCT.Liver and CoagulationAH promotes coagulation disturbances following trauma and acidosis by reducing coagulation and platelet functions. Mean prothrombin and partial thromboplastin times might increase by 40–60% in moderate hypothermia. Rewarming might release tissue factor from damaged tissues, that triggers disseminated intravascular coagulation. Hypothermia might inhibit platelet aggregation and coagulation.KidneysRenal blood flow decreases due to vasoconstriction of afferent arterioles, electrolyte and fluid disturbances and increasing blood viscosity. Severely deranged renal function occurs particularly in the presence of rhabdomyolysis induced by severe AH combined with trauma.ConclusionMetabolism drops 7% per °C fall in BCT, reducing CO correspondingly. Therefore, it is possible to maintain adequate oxygen delivery after 10°C drop in BCT provided correctly performed CPR. Hypothermia may facilitate rhabdomyolysis in traumatized patients. Victims suspected of HCA should be rewarmed before being pronounced dead. Rewarming avalanche victims of HCA with serum potassium > 12 mmol/L and a burial time >30 min with no air pocket, most probably be futile.

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Section: Hypothermia-induced Changes In Organ Functionsmentioning

confidence: 99%

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update

et al. 2022

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“…Clinical guidelines recommend therapeutic hypothermia should be started as early as possible within 6 h of birth and continued for a period of 72 h, with a target brain temperature of 33.5 ± 0.5 °C [ 77 ]. Therapeutic hypothermia is associated with immunosuppressive changes [ 155 ], including inhibition of microglial activation, chemotaxis, production of pro-inflammatory cytokines, and nuclear translocation nuclear factor kappa-B [ 156 , 157 , 158 ]. Confirming extensive preclinical evidence [ 159 ], a meta-analysis of 11 randomized controlled trials of systemic and head cooling in infants with HIE (≥ 35-week gestation) showed that hypothermia reduces brain damage on imaging after rewarming [ 160 ], and improves survival without disability at 18 to 24 months of age [ 129 ].…”

Section: Treatmentmentioning

confidence: 99%

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Ophelders

Gussenhoven

Klein

et al. 2020

Cells

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With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks’ gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that include antenatal infection (i.e., chorioamnionitis), hypoxia-ischemia, and various postnatal injurious triggers (i.e., oxidative stress, sepsis, mechanical ventilation, hemodynamic instability). These perinatal insults cause a self-perpetuating cascade of peripheral and cerebral inflammation that plays a critical role in the etiology of diffuse white and grey matter injuries that underlies a spectrum of connectivity deficits in survivors from extremely preterm birth. This review focuses on chorioamnionitis and hypoxia-ischemia, which are two important antenatal risk factors for preterm brain injury, and highlights the latest insights on its pathophysiology, potential treatment, and future perspectives to narrow the translational gap between preclinical research and clinical applications.

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“…However, pharmacological treatments were solely focused on neurons. Gradually, glial cells started to be considered as alternative targets for neuroprotection [9][10].…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Biomarkers and Pathways in Neonatal Hypoxic-Ischemic Brain Injury: Based on Bioinformatics Technology

Li¹,

Li²,

Zhao³

et al. 2021

Preprint

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Background Neonatal hypoxic-ischemic brain damage (HIBD) is one of the most common serious diseases in newborns, with a high mortality and disability rate. This study aims to use the bioinformatics analysis to identify potential hematologic/immune systems tissue-specific genes and related signaling pathways neonatal HIBD.Methods Microarray datasets in HIBD were downloaded from the Gene Expression Omnibus database, and DEGs were identified by R software.Enrichment analyses were performed and protein–protein interaction networks were constructed to understand the functions and enriched pathways of DEGs and to identify central genes and key modules. Results In the cerebral cortex tissue with HIBD, 2598 DEGs were identified, including 2362 up-regulated and 236 down-regulated DEGs. In the blood with HIBD, 1442 DEGs were identified, including 540 up-regulated and 902 down-regulated DEGs. The results of biological processes and KEGG enrichment were very similar in DEGs of the two kinds of tissues, and both involved inflammation, immunity and apoptosis. The common DEGs of the two kinds of tissues also showed similar results in biological processes and KEGG enrichment.and four hematologic/immune system tissues specifically expressed potential biomarker genes were confirmed through a variety of methods, which were verified by GEO datasets and published experimental research. Conclusion The DEGs of HIBD including the potential peripheral biomarkers TYROBP, ITGAM, EGR1 and HMOX1, which may play a role in the pathogenesis of HIBD through inflammation and immune-mediated signaling pathways.

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Cooling and immunomodulation for treating hypoxic‐ischemic brain injury

Cited by 20 publications

References 86 publications

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Identification of Potential Biomarkers and Pathways in Neonatal Hypoxic-Ischemic Brain Injury: Based on Bioinformatics Technology

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