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Hypothermia neuroprotection

Robert Galinsky, Joanne O Davidson, Justin M Dean, Colin R Green, Laura Bennet, Alistair J Gunn
Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypothermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction (connexin) hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation...
February 2018: Neural Regeneration Research
Divyen K Shah, Vennila Ponnusamy, Jane Evanson, Olga Kapellou, Georgia Ekitzidou, Neelam Gupta, Paul Clarke, Adina T Michael-Titus, Ping K Yip
Aims and hypothesis: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was to show that it is feasible to study plasma neurofilament light (NfL) levels from newborns and to evaluate their temporal course. Hypothesis: Raised plasma NFL protein levels from newborns who undergo TH after HIE are associated with abnormal MRI outcomes...
2018: Frontiers in Neurology
Heather Campbell, Rathinaswamy B Govindan, Srinivas Kota, Tareq Al-Shargabi, Marina Metzler, Nickie Andescavage, Taeun Chang, Gilbert Vezina, Adre du Plessis, An N Massaro
OBJECTIVE: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury. STUDY DESIGN: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia...
March 6, 2018: Journal of Pediatrics
Sandra E Juul, Bryan A Comstock, Patrick J Heagerty, Dennis E Mayock, Amy M Goodman, Stephanie Hauge, Fernando Gonzalez, Yvonne W Wu
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, and to describe a new phase III randomized, placebo-controlled trial of Epo neuroprotection in term and near-term infants with moderate to severe HIE treated with therapeutic hypothermia...
March 7, 2018: Neonatology
Nazli Kuter, Nese Aysit-Altuncu, Gurkan Ozturk, Eren Ozek
BACKGROUND: In high-risk newborns indirect hyperbilirubinemia can lead to acute bilirubin encephalopathy and kernicterus. Despite the current therapeutic modalities, preventing or reversing the neurotoxicity cannot be achieved in all infants. OBJECTIVE: To investigate the neuroprotective effects of hypothermia on bilirubin-induced toxicity in primary mouse neuronal cell cultures. METHODS: Hippocampal cell cultures, isolated from newborn mouse brains, were incubated with unconjugated bilirubin (UCB) at 3 days in vitro (DIV) and immediately exposed to varying degrees of hypothermia...
March 6, 2018: Neonatology
Lina Chalak, Samantha Latremouille, Imran Mir, Pablo J Sánchez, Guilherme Sant'Anna
A review of the conundrum called mild hypoxic-ischemic encephalopathy (HIE) is provided. During the past decades, the definition of HIE has evolved to accommodate the short window of time required for the initiation of therapeutic hypothermia. Also, neurological evaluations have changed with the use of simpler staging systems that can be applied within the first 6 h of life. In this review, we discuss the challenges in the identification of newborns with "mild HIE" within 6 h after birth, the limitations in the existing early biomarkers of brain injury, and the current knowledge gaps in the long term neurodevelopmental outcomes of infants diagnosed with mild HIE...
March 2, 2018: Early Human Development
Fred Rincon
Evidence from animal models indicates that lowering temperature by a few degrees can produce substantial neuroprotection. In humans, hypothermia has been found to be neuroprotective with a significant impact on mortality and long-term functional outcome only in cardiac arrest and neonatal hypoxic-ischemic encephalopathy. Clinical trials have explored the potential role of maintaining normothermia and treating fever in critically ill brain injured patients. This review concentrates on basic concepts to understand the physiologic interactions of thermoregulation, effects of thermal modulation in critically ill patients, proposed mechanisms of action of temperature modulation, and practical aspects of targeted temperature management...
April 2018: Neurosurgery Clinics of North America
Shadnaz Asgari, Hana Moshirvaziri, Fabien Scalzo, Nima Ramezan-Arab
Cardiac arrest (CA) is the leading cause of death and disability in the United States. Early and accurate prediction of CA outcome can help clinicians and families to make a better-informed decision for the patient's healthcare. Studies have shown that electroencephalography (EEG) may assist in early prognosis of CA outcome. However, visual EEG interpretation is subjective, labor-intensive, and requires interpretation by a medical expert, i.e., neurophysiologists. These limiting factors may hinder the applicability of such testing as the prognostic method in clinical settings...
February 26, 2018: Journal of Clinical Monitoring and Computing
Henry H Cheng, Satish K Rajagopal, Arnold J Sansevere, Erica McDavitt, Daniel Wigmore, Jessica Mecklosky, Kristofer Andren, Kathryn Williams, Amy Danehy, Janet S Soul
BACKGROUND: While therapeutic hypothermia (TH) is an effective neuroprotective therapy for neonatal hypoxic-ischemic encephalopathy, TH has not been demonstrated to improve outcome in other pediatric populations. Patients with acquired or congenital heart disease (CHD) are at high risk of both cardiac arrest and neurodevelopmental impairments, and therapies are needed to improve neurologic outcome. The primary goal of our study was to compare safety/efficacy outcomes in post-arrest CHD patients treated with TH versus controls not treated with TH...
February 21, 2018: Resuscitation
Molly Potter, Ted Rosenkrantz, R Holly Fitch
The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981). This preparation models brain injury seen in premature infants (gestational age (GA) 32-35 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language/learning disabilities...
February 21, 2018: International Journal of Developmental Neuroscience
Hans Jørgen Timm Guthe, Torbjørn Nedrebø, Jan Kristian Damås, Helge Wiig, Ansgar Berg
BACKGROUND: Therapeutic hypothermia is neuroprotective in asphyxiated neonates by counteracting mechanisms contributing to brain injury. Although an initial increased permeability is part of an inflammatory reaction and thereby a natural healing process, an excessive endothelial permeability with edema formation may result in impaired hemodynamics. Reduced permeability may, however, benefit healing. Although plasma and interstitial colloid osmotic pressure are accessible and essential parameters for understanding fluid imbalance, the mechanisms of fluid exchange remain poorly understood...
February 23, 2018: BMC Pediatrics
Ericka L Fink, Robert S B Clark, Rachel P Berger, Anthony Fabio, Derek C Angus, R Scott Watson, John J Gianakas, Ashok Panigrahy, Clifton W Callaway, Michael J Bell, Patrick M Kochaneka
AIM: Children surviving cardiac arrest (CA) lack proven neuroprotective therapies. The role of biomarkers in assessing response to interventions is unknown. We hypothesized that 72 versus 24 h of hypothermia (HT) would produce more favorable biomarker profiles after pediatric CA. METHODS: This single center pilot randomized trial tested HT (33 ± 1 °C) for 24 vs. 72 h in 34 children with CA. Children comatose after return of circulation aged 1 week to 17 years and treated with HT by their physician were eligible...
February 14, 2018: Resuscitation
Mark S Wainwright
PURPOSE OF REVIEW: All critical care is directed at maintaining brain health, but recognizing neurologic complications of critical illness in children is difficult, and limited data exist to guide practice. This article discusses an approach to the recognition and management of seizures, stroke, and cardiac arrest as complications of other critical illnesses in the pediatric intensive care unit. RECENT FINDINGS: Convulsive and nonconvulsive seizures occur frequently in children after cardiac arrest or traumatic brain injury and during extracorporeal membrane oxygenation...
February 2018: Continuum: Lifelong Learning in Neurology
Shin Nakayama, Noriko Taguchi, Makoto Tanaka
The hydrogen sulfide donor sodium hydrogen sulfide (NaHS) is recognized as a neuroprotective agent, which induces a hibernation-like metabolic state and hypothermia. However, it remains unclear whether it is the sulfide itself or the hypothermia induced by the sulfide that mediates treatment outcomes following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). We therefore tested whether NaHS improved outcomes following CA/CPR in mice maintained at 35.0°C by active warming during recovery. Adult male mice were subjected to 8 minutes CA/CPR and randomly treated intraperitoneally with either implantation of miniosmotic pump with NaHS (50 μmol/kg/day) for 3 days or vehicle 30 minutes after CPR...
February 12, 2018: Therapeutic Hypothermia and Temperature Management
Artem Pastukhov, Tatiana Borisova
Deep and profound hypothermia is successfully practiced in the prevention of ischemic stroke consequences and aortic arch cardiac surgery accompanied by reduction of cerebral circulation. Hypothermia is a current neuroprotection standard in hypoxic/ischemic encephalopathy. Drug-hypothermia administration is proposed as a new approach in pharmacotherapy for neonatal seizures. Also, hypothermia is useful as neuroprotective approach in long-term interplanetary space missions. We recently revealed gradual dynamics of hypothermia-induced decrease in transporter-mediated release and uptake of L-[14C]glutamate in presynaptic rat brain nerve terminals (synaptosomes), thereby confirming potent unspecific neuroprotective effect of hypothermia...
February 8, 2018: Therapeutic Hypothermia and Temperature Management
Ingran Lingam, Nicola J Robertson
Magnesium is an intracellular cation essential for many en-zymatic processes and cellular functions. Magnesium sulfate acts as an endogenous calcium channel antagonist at neuronal synapses, thought to prevent excessive activation of N-methyl-D-aspartate receptors by excitatory amino acids, such as glutamate, and by downregulation of proinflammatory pathways. Early intervention is essential in the prevention of the secondary phase of neuronal injury. The immature brain is particularly prone to excitotoxicity, and inflammation has been strongly implicated in the pathogenesis of cerebral palsy...
February 7, 2018: Developmental Neuroscience
Stefania Gedrova, Jan Galik, Martin Marsala, Monika Zavodska, Jaroslav Pavel, Igor Sulla, Miroslav Gajdos, Imrich Lukac, Jozef Kafka, Valent Ledecky, Igor Sulla, Martina Karasova, Peter Reichel, Alexandra Trbolova, Igor Capik, Viktoria Lukacova, Katarina Bimbova, Maria Bacova, Andrea Stropkovska, Nadezda Lukacova
This study investigated the neuroprotective efficacy of local hypothermia in a minipig model of spinal cord injury (SCI) induced by a computer-controlled impactor device. The tissue integrity observed at the injury epicenter, and up to 3 cm cranially and caudally from the lesion site correlated with motor function. A computer-controlled device produced contusion lesions at L3 level with two different degrees of tissue sparing, depending upon pre-set impact parameters (8N- and 15N-force impact). Hypothermia with cold (4°C) saline or Dulbecco's modified Eagle's medium (DMEM)/F12 culture medium was applied 30 min after SCI (for 5 h) via a perfusion chamber (flow 2 ml/min)...
January 2018: Experimental and Therapeutic Medicine
Peng Wang, Yi Li, Zhengfei Yang, Tao Yu, Guanghui Zheng, Xiangshao Fang, Zitong Huang, Longyuan Jiang, Wanchun Tang
Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates cerebral ischemic injury after cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: Mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12)...
January 8, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Elisa Landucci, Luca Filippi, Elisabetta Gerace, Serena Catarzi, Renzo Guerrini, Domenico E Pellegrini-Giampietro
Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and subsequent severe neurological sequelae. Mild hypothermia is a standard therapy for HIE, but is used only in selected Reference Centers and in neonates >1800 g. Since neuronal death following HIE occurs by a cascade of events triggered by activation of glutamate receptors, we used in vitro and in vivo models of HIE to examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA receptor antagonist memantine could exert neuroprotective effects, alone or in combination with hypothermia...
January 12, 2018: Neuroscience Letters
Dan Yu, Xueying Wang, Feng Zhou, Liang Wang, Guoshuai Yang, Wei Zhong, Ying Li, Zhiping Zhou, Aiyue Wang, Yanhui Zhou
We assessed neurological outcomes, infarct volume, and the expression of nestin and caspase-3 in the hippocampal dentate gyrus following middle cerebral artery occlusion (MCAO) followed by reperfusion, with mild hypothermia (MH) treatment at the onset of ischemia in a MCAO rat model. Reperfusion began 2 hours after the MCAO model was set-up. MH treatment began at the onset of ischemia and was maintained for 4 hours. We evaluated neurological deficit score, brain infarct volumes, along with the immunohistochemical staining of nestin and caspase-3 in the sub-granular zone of the injured hemisphere on the 1st, 3rd, 7th, and 14th day after the onset of ischemia...
December 12, 2017: Oncotarget
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