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Hypothermia neuroprotection

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https://www.readbyqxmd.com/read/28407632/hypothermic-neuronal-rescue-from-infection-sensitised-hypoxic-ischaemic-brain-injury-is-pathogen-dependent
#1
Mari Falck, Damjan Osredkar, Elke Maes, Torun Flatebø, Thomas Ragnar Wood, Hemmen Sabir, Marianne Thoresen
Perinatal infection increases the vulnerability of the neonatal brain to hypoxic-ischaemic (HI) injury. Hypothermia treatment (HT) does not provide neuroprotection after pre-insult inflammatory sensitisation by lipopolysaccharide (LPS), a gram-negative bacterial wall constituent. However, early-onset sepsis in term babies is caused by gram-positive species in more than 90% of cases, and neuro-inflammatory responses triggered through the gram-negative route (Toll-like receptor 4, TLR-4) are different from those induced through the gram-positive route via TLR-2...
April 14, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28391258/dexmedetomidine-combined-with-therapeutic-hypothermia-is-associated-with-cardiovascular-instability-and-neurotoxicity-in-a-piglet-model-of-perinatal-asphyxia
#2
Mojgan Ezzati, Go Kawano, Eridan Rocha-Ferreira, Daniel Alonso-Alconada, Jane K Hassell, Kevin D Broad, Igor Fierens, Bobbi Fleiss, Alan Bainbridge, David L Price, Pardis Kaynezhad, Brian Anderson, Mariya Hristova, Ilias Tachtsidis, Xavier Golay, Pierre Gressens, Robert D Sanders, Nicola J Robertson
The selective α2-adrenoreceptor agonist dexmedetomidine has shown neuroprotective, analgesic, anti-inflammatory, and sympatholytic properties that may be beneficial in neonatal encephalopathy (NE). As therapeutic hypothermia is only partially effective, adjunct therapies are needed to optimize outcomes. The aim was to assess whether hypothermia + dexmedetomidine treatment augments neuroprotection compared to routine treatment (hypothermia + fentanyl sedation) in a piglet model of NE using magnetic resonance spectroscopy (MRS) biomarkers, which predict outcomes in babies with NE, and immunohistochemistry...
April 8, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28377304/longitudinal-mri-evaluation-of-neuroprotective-effects-of-pharmacologically-induced-hypothermia-in-experimental-ischemic-stroke
#3
Silun Wang, Xiaohuan Gu, Ramesh Paudyal, Ling Wei, Thomas A Dix, Shan P Yu, Xiaodong Zhang
Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection...
April 2, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28366066/neuroprotective-strategies-and-the-underlying-molecular-basis-of-cerebrovascular-stroke
#4
REVIEW
Michael Karsy, Andrea Brock, Jian Guan, Phillip Taussky, M Yashar S Kalani, Min S Park
Stroke is a leading cause of disability in the US. Although there has been significant progress in the area of medical and surgical thrombolytic technologies, neuroprotective agents to prevent secondary cerebral injury and to minimize disability remain limited. Only limited success has been reported in preclinical and clinical trials evaluating a variety of compounds. In this review, the authors discuss the most up-to-date information regarding the underlying molecular biology of stroke as well as strategies that aim to mitigate this complex signaling cascade...
April 2017: Neurosurgical Focus
https://www.readbyqxmd.com/read/28355608/new-wavelet-neurovascular-bundle-for-bedside-evaluation-of-cerebral-autoregulation-and-neurovascular-coupling-in-newborns-with-hypoxic-ischemic-encephalopathy
#5
Lina F Chalak, Rong Zhang
Neonatal encephalopathy (NE) resulting from birth asphyxia constitutes a major global public health burden for millions of infants every year, and despite therapeutic hypothermia, half of these neonates have poor neurological outcomes. As new neuroprotective interventions are being studied in clinical trials, there is a critical need to establish physiological surrogate markers of therapeutic efficacy, to guide patient selection and/or to modify the therapeutic intervention. The challenge in the field of neonatal brain injury has been the difficulty of clinically discerning NE severity within the short therapeutic window after birth or of analyzing the dynamic aspects of the cerebral circulation in sick NE newborns...
March 30, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28351056/comparison-of-umbilical-serum-copeptin-relative-to-erythropoietin-and-s100b-as-asphyxia-biomarkers-at-birth
#6
Milla Summanen, Laura Seikku, Petri Rahkonen, Vedran Stefanovic, Kari Teramo, Sture Andersson, Kai Kaila, Leena Rahkonen
BACKGROUND: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. OBJECTIVES: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B...
March 29, 2017: Neonatology
https://www.readbyqxmd.com/read/28350947/traumatic-spinal-cord-injury-repair-and-regeneration
#7
Christopher S Ahuja, Satoshi Nori, Lindsay Tetreault, Jefferson Wilson, Brian Kwon, James Harrop, David Choi, Michael G Fehlings
BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery. PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28306631/thermoregulate-autoregulate-and-ventilate-brain-directed-critical-care-for-pediatric-cardiac-arrest
#8
Jonathan E Kurz, Craig M Smith, Mark S Wainwright
PURPOSE OF REVIEW: Cardiac arrest in childhood is associated with a high risk for mortality and poor long-term functional outcome. This review discusses the current evidence for neuroprotective therapies and goals for postarrest care in the context of the pathophysiology of hypoxic-ischemic injury, modalities for neurologic prognostication in these children and potential future monitoring paradigms for maximizing cerebral perfusion in the postarrest period. RECENT FINDINGS: The recent publication of the in-hospital and out-of-hospital Therapeutic Hypothermia After Cardiac Arrest trials demonstrated a lack of statistically significant benefit for the use of postarrest therapeutic hypothermia...
March 16, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28292952/hypothermia-induced-neuroprotection
#9
Annalisa M VanHook
A reticulon contributes to the neuroprotective effects of hypothermia.
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28288145/rectal-temperature-in-the-first-five-hours-after-hypoxia-ischaemia-critically-affects-neuropathological-outcomes-in-neonatal-rats
#10
Thomas Wood, Catherine Hobbs, Mari Falck, Anne Charlotte Brun, Else Marit Løberg, Marianne Thoresen
BACKGROUND: Hyperthermia after hypoxia-ischaemia (HI) in newborn infants is associated with worse neurological outcomes. Loss of thermoregulation may also be associated with greater injury. METHODS: In the postnatal-day 7 (P7) rat, the effect of 5h of graded hyperthermia (38°C or 39°C) immediately after unilateral HI was compared to normothermia (NT, 37°C), and therapeutic hypothermia (TH, 32°C). Early (negative geotaxis) and late (staircase test) behavioural testing was performed, as well as neuropathology scoring in adulthood...
March 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28285429/hypothermia-decreased-the-expression-of-heat-shock-proteins-in-neonatal-rat-model-of-hypoxic-ischemic-encephalopathy
#11
Byong Sop Lee, Euiseok Jung, Yeonjoo Lee, Sung-Hoon Chung
Hypothermia (HT) is a well-established neuroprotective strategy against neonatal hypoxic ischemic encephalopathy (HIE). The overexpression of heat shock proteins (HSP) has been shown to provide neuroprotection in animal models of stroke. We aimed to investigate the effect of HT on HSP70 and HSP27 expression in a neonatal rat model of HIE. Seven-day-old rat pups were exposed to hypoxia for 90 min to establish the Rice-Vannucci model and were assigned to the following four groups: hypoxic injury (HI)-normothermia (NT, 36 °C), HI-HT (30 °C), sham-NT, and sham-HT...
March 11, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28277490/erythropoietin-monotherapy-in-perinatal-asphyxia-with-moderate-to-severe-encephalopathy-a-randomized-placebo-controlled-trial
#12
R R Malla, R Asimi, M A Teli, F Shaheen, M A Bhat
OBJECTIVE: Erythropoietin (EPO) is neuroprotective after asphyxia in animal studies. The efficacy and safety of EPO monotherapy in term neonates with hypoxic ischemic encephalopathy (HIE) is uncertain. STUDY DESIGN: Hundred term neonates with moderate or severe HIE were randomized by random permuted block algorithm to receive either EPO 500 U kg(-1) per dose in 2 ml saline intravenously (50 neonates) on alternate days for a total of five doses with the first dose given by 6 h of age (treatment group) or 2 ml of normal saline (50 neonates) similarly for a total of five doses (placebo group) in a double-blind study...
March 9, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28268879/optimal-control-of-inspired-perfluorocarbon-temperature-for-induction-of-hypothermia-by-total-liquid-ventilation-in-juvenile-lamb-model
#13
Mathieu Nadeau, Michael Sage, Jean-Paul Praud, Renaud Tissier, Herve Walti, Philippe Micheau
Mild hypothermia is well known for its therapeutic value in cardio- and neuroprotection. Many recent experimental studies have shown that the swiftness of the cooling offered by total liquid ventilation (TLV) holds great promise in achieving maximal therapeutic effect. TLV is an emerging ventilation technique in which the lungs are filled with breathable liquids, namely perfluorocarbons (PFCs). A liquid ventilator ensures subject ventilation by periodically renewing a volume of oxygenated, CO2-free and temperature-controlled breathable PFC...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268471/examining-the-effect-of-mgso4-on-sharp-wave-transient-activity-in-the-hypoxic-ischemic-fetal-sheep-model
#14
Meherzad J Lakadia, Hamid Abbasi, Alistair J Gunn, Charles P Unsworth, Laura Bennet
Hypoxic-ischemic encephalopathy (HIE) due to lack of oxygen is a debilitating disorder experienced by a significant number of preterm infants during birth. Studies show that the brain undergoes different phases of injury following hypoxic insult, but the first 6-8 hours (known as a latent phase) are the key to treatment efficacy. Cerebral hypothermia is one known treatment, and for it to be effective it must be started during the latent phase and continued for several days. In order to determine the effectiveness of treatment it is important to pinpoint the time of insult...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28253907/systemic-pro-inflammatory-cytokine-status-following-therapeutic-hypothermia-in-a-piglet-hypoxia-ischemia-model
#15
Eridan Rocha-Ferreira, Dorottya Kelen, Stuart Faulkner, Kevin D Broad, Manigandan Chandrasekaran, Áron Kerenyi, Takenori Kato, Alan Bainbridge, Xavier Golay, Mark Sullivan, Boris W Kramer, Nicola J Robertson
BACKGROUND: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines...
March 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28252661/predictive-value-of-amplitude-integrated-eeg-aeeg-after-rescue-hypothermic-neuroprotection-for-hypoxic-ischemic-encephalopathy-a-meta-analysis
#16
M Chandrasekaran, B Chaban, P Montaldo, S Thayyil
OBJECTIVE: Amplitude-integrated electroencephalography (aEEG) is a useful bedside tool in predicting the neurodevelopmental outcome after neonatal encephalopathy; however, the prognostic accuracy may be altered by rescue hypothermic neuroprotection. The objective of this study is to examine the prognostic accuracy of aEEG for predicting long-term neurodevelopmental outcomes in term newborn infants undergoing therapeutic hypothermia for neonatal encephalopathy. STUDY DESIGN: We examined all studies (Medline, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library; 2000 to 2014) comparing aEEG (6, 24, 48 or 72 h) in term encephalopathic babies undergoing therapeutic hypothermia, with neurodevelopmental outcome at 1 year or more...
March 2, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28250763/molecular-chaperones-and-hypoxic-ischemic-encephalopathy
#17
REVIEW
Cong Hua, Wei-Na Ju, Hang Jin, Xin Sun, Gang Zhao
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28243991/normothermia-and-stroke
#18
REVIEW
Jonathan Marehbian, David M Greer
In the past two decades, there has been much focus on the adverse effect of fever on neurologic outcome, the benefits of hypothermia on functional outcomes, and the interplay of associated complications. Despite decades of experience regarding randomized, safety and feasibility, case-controlled, retrospective studies, there has yet to be a large, randomized, multicenter, clinical trial with the appropriate power to address the potential benefits of targeted temperature modulation compared to hypothermia alone...
January 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28242326/therapeutic-hypothermia-attenuates-global-cerebral-reperfusion-induced-mitochondrial-damage-by-suppressing-dynamin-related-protein-1-activation-and-mitochondria-mediated-apoptosis-in-a-cardiac-arrest-rat-model
#19
Jingjing Fan, Shenquan Cai, Hao Zhong, Liangbin Cao, Kangli Hui, Miaomiao Xu, Manlin Duan, Jianguo Xu
Therapeutic hypothermia is effective to attenuate brain ischemia/reperfusion (I/R) injury after cardiac arrest, and multiple mechanisms have been proposed. Dynamin-related protein 1 (Drp1), a large GTPases of dynamin superfamily, predominantly controls mitochondrial fission and is related to IR-induced Cyt C release and apoptosis. However, the effect of therapeutic hypothermia on Drp1 and mitochondrial fission after cardiac arrest remains still unclear. In this study, non-cardiac arrest and post-cardiac arrest rats received 6-h normothermia (37-38°C) or therapeutic hypothermia (32-34°C), and the hippocampus was harvested at 6h and 72h after cardiac arrest...
February 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28238655/rtn3-is-a-novel-cold-induced-protein-and-mediates-neuroprotective-effects-of-rbm3
#20
Amandine Bastide, Diego Peretti, John R P Knight, Stefano Grosso, Ruth V Spriggs, Xavier Pichon, Thomas Sbarrato, Anne Roobol, Jo Roobol, Davide Vito, Martin Bushell, Tobias von der Haar, C Mark Smales, Giovanna R Mallucci, Anne E Willis
Cooling and hypothermia are profoundly neuroprotective, mediated, at least in part, by the cold shock protein, RBM3. However, the neuroprotective effector proteins induced by RBM3 and the mechanisms by which mRNAs encoding cold shock proteins escape cooling-induced translational repression are unknown. Here, we show that cooling induces reprogramming of the translatome, including the upregulation of a new cold shock protein, RTN3, a reticulon protein implicated in synapse formation. We report that this has two mechanistic components...
March 6, 2017: Current Biology: CB
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