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Hypothermia neuroprotection

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https://www.readbyqxmd.com/read/28504050/how-long-is-sufficient-for-optimal-neuroprotection-with-cerebral-cooling-after-ischemia-in-fetal-sheep
#1
Joanne O Davidson, Vittoria Draghi, Sean Whitham, Simerdeep K Dhillon, Guido Wassink, Laura Bennet, Alistair J Gunn
The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28469636/neuroprotective-mechanisms-and-translational-potential-of-therapeutic-hypothermia-in-the-treatment-of-ischemic-stroke
#2
REVIEW
Jin Hwan Lee, James Zhang, Shan Ping Yu
Stroke is a leading cause of disability and death, yet effective treatments for acute stroke has been very limited. Thus far, tissue plasminogen activator has been the only FDA-approved drug for thrombolytic treatment of ischemic stroke patients, yet its application is only applicable to less than 4-5% of stroke patients due to the narrow therapeutic window (< 4.5 hours after the onset of stroke) and the high risk of hemorrhagic transformation. Emerging evidence from basic and clinical studies has shown that therapeutic hypothermia, also known as targeted temperature management, can be a promising therapy for patients with different types of stroke...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28452885/optimization-of-brain-metabolism-using-metabolic-targeted-therapeutic-hypothermia-can-reduce-mortality-from-traumatic-brain-injury
#3
Jin-Zhou Feng, Wen-Yuan Wang, Jun Zeng, Zhi-Yuan Zhou, Jin Peng, Hao Yang, Peng-Chi Deng, Shi-Jun Li, Charles D Lu, Hua Jiang
BACKGROUND: Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target as optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof...
April 27, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28450915/emulsified-isoflurane-combined-with-therapeutic-hypothermia-improves-survival-and-neurological-outcomes-in-a-rat-model-of-cardiac-arrest
#4
Meng-Jun Wu, Ya-Jie Zhang, Hai Yu, Bin Liu
Emulsified isoflurane (EIso), when introduced following cardiopulmonary resuscitation (CPR), significantly improves survival and neurological outcomes in a rat model of cardiac arrest (CA). The present study aimed to examine whether EIso combined with therapeutic hypothermia (TH) confers an additive neuroprotective effect. Adult male Sprague-Dawley rats that were subjected to return of spontaneous circulation (ROSC) after a 6-min asphyxia-induced CA were randomized to five groups: Sham group, control group under normothermic conditions, EIso group (4 ml/kg for 30 min under normothermic conditions), TH group (33°C for 2 h), and EIso plus TH group...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28448965/neuroprotective-treatments-after-perinatal-hypoxic-ischemic-brain-injury-evaluated-with-magnetic-resonance-spectroscopy
#5
Hester Rijkje Berger, Eva Brekke, Marius Widerøe, Tora Sund Morken
Perinatal hypoxic-ischemic brain injury is a major health problem. Adjuvant treatments that improve the neuroprotective effect of the current treatment, therapeutic hypothermia, are urgently needed. The growing knowledge about the complex pathophysiology of hypoxia-ischemia (HI) has led to the discovery of several important targets for neuroprotection. Early interventions should focus on the preservation of energy metabolism, the reduction of glutamate excitotoxicity and oxidative stress, the maintenance of calcium homeostasis, and the prevention of apoptosis...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28407632/hypothermic-neuronal-rescue-from-infection-sensitised-hypoxic-ischaemic-brain-injury-is-pathogen-dependent
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
June 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28292952/hypothermia-induced-neuroprotection
#14
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
#15
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
#16
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...
May 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
#17
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
#18
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
#19
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
#20
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
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