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Hypothermia neuroprotection

David R Busch, Craig G Rusin, Wanda Miller-Hance, Kathy Kibler, Wesley B Baker, Jeffrey S Heinle, Charles D Fraser, Arjun G Yodh, Daniel J Licht, Kenneth M Brady
While survival of children with complex congenital heart defects has improved in recent years, roughly half suffer neurological deficits suspected to be related to cerebral ischemia. Here we report the first demonstration of optical diffuse correlation spectroscopy (DCS) for continuous and non-invasive monitoring of cerebral microvascular blood flow during complex human neonatal or cardiac surgery. Comparison between DCS and Doppler ultrasound flow measurements during deep hypothermia, circulatory arrest, and rewarming were in good agreement...
September 1, 2016: Biomedical Optics Express
Nagat Mohammed, Maria Ceprián, Laura Jimenez, M Ruth Pazos, Jose Martínez-Orgado
BACKGROUND: A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage. OBJECTIVE: to test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage. METHOD: 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation)...
September 27, 2016: CNS & Neurological Disorders Drug Targets
Tiffany D Stafford, Joseph L Hagan, Curtis G Sitler, Caraciolo J Fernandes, Jeffrey R Kaiser
Perinatal hypoxic ischemic encephalopathy (HIE) can lead to severe neurodevelopmental outcome and death. Therapeutic hypothermia is neuroprotective for infants with moderate-to-severe HIE. However, therapeutic hypothermia is only offered at high-level regional neonatal intensive care units (NICUs), necessitating the need to transport sick infants to referral centers. The goal of this study was to evaluate whether active cooling on transport is more effective than passive cooling in achieving temperatures in the treatment target range (33°C-34°C) on arrival to the Texas Children's Hospital (TCH) NICU...
September 27, 2016: Therapeutic Hypothermia and Temperature Management
Alistair J Gunn, Abbot R Laptook, Nicola J Robertson, John D Barks, Marianne Thoresen, Guido Wassink, Laura Bennet
Acute post-asphyxial encephalopathy around the time of birth remains a major cause of death and disability. The possibility that hypothermia may be able to prevent or lessen asphyxial brain injury is a "dream revisited". In this review, a historical perspective is provided from the first reported use of therapeutic hypothermia for brain injuries in antiquity, to the present day. The first uncontrolled trials of cooling for resuscitation were reported more than 50 years ago. The seminal insight that led to the modern revival of studies of neuroprotection was that after profound asphyxia, many brain cells show initial recovery from the insult during a short "latent" phase, typically lasting approximately 6 h, only to die hours to days later after a "secondary" deterioration characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism...
September 27, 2016: Pediatric Research
N Subirós, H Pérez-Saad, L Aldana, C L Gibson, W S Borgnakke, D Garcia-Del-Barco
BACKGROUND: Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. OBJECTIVES: The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke...
September 26, 2016: Neurological Research
Kota Kurisu, Takeo Abumiya, Masaki Ito, Masayuki Gekka, Toshiya Osanai, Hideo Shichinohe, Naoki Nakayama, Ken Kazumata, Kiyohiro Houkin
The robust neuroprotective effects of transarterial regional hypothermia have been demonstrated in the typical transient middle cerebral artery occlusion (tMCAO) model, but have not yet been tested in other ischemic stroke models, even though clinical ischemic conditions are diverse. In order to clarify these effects in a different ischemic stroke model, we employed a rat model of permanent MCAO (pMCAO) with transient collateral hypoperfusion (tCHP), which was achieved by direct MCA ligation through craniotomy and 1-hour bilateral common carotid artery occlusion at the beginning of pMCAO...
September 20, 2016: Brain Research
Jennifer K Lee, Bing Wang, Michael Reyes, Jillian S Armstrong, Ewa Kulikowicz, Polan T Santos, Jeong-Hoo Lee, Raymond C Koehler, Lee J Martin
Therapeutic hypothermia provides incomplete neuroprotection after hypoxia-ischemia (HI)-induced brain injury in neonates. We previously showed that cortical neuron and white matter apoptosis are promoted by hypothermia and early rewarming in a piglet model of HI. The unfolded protein response (UPR) may be one of the potential mediators of this cell death. Here, neonatal piglets underwent HI or sham surgery followed by 29 h of normothermia, 2 h of normothermia + 27 h of hypothermia or 18 h of hypothermia + rewarming...
September 14, 2016: Developmental Neuroscience
Mathilde Chevin, Clémence Guiraut, Caroline Maurice-Gelinas, Jessica Deslauriers, Sylvain Grignon, Guillaume Sébire
BACKGROUND: Despite the recent introduction of hypothermia as a mandatory standard of care, the incidence of neonatal encephalopathy in full-term newborns and its devastating neuro-behavioral outcomes continues to be a major individual, familial and social issue. Neonatal encephalopathy is mainly due to the compounding and interacting effects of hypoxia-ischemia and inflammation resulting from placental and other perinatal infections. It is unclear why hypothermia is effective in alleviating neonatal encephalopathy in some, but not all, full-term newborns...
September 9, 2016: International Journal of Developmental Neuroscience
Angie C Jelin, Kirsten Salmeen, Dawn Gano, Irina Burd, Mari-Paule Thiet
Antepartum, intrapartum, and neonatal events can result in a spectrum of long-term neurological sequelae, including cerebral palsy, cognitive delay, schizophrenia, and autism spectrum disorders [1]. Advances in obstetrical and neonatal care have led to survival at earlier gestational ages and consequently increasing numbers of periviable infants who are at significant risk for long-term neurological deficits. Therefore, efforts to decrease and prevent cerebral insults attempt not only to decrease preterm delivery but also to improve neurological outcomes in infants delivered preterm...
2016: F1000Research
Ou Lv, Fenggang Zhou, Yongri Zheng, Qingsong Li, Jianjiao Wang, Yulan Zhu
Subarachnoid hemorrhage (SAH) is a severe neurological disease, which is associated with a significant number of cases of premature mortality and disability worldwide. Mild hypothermia (MH) has been proposed as a potential therapeutic strategy to reduce neuronal injury following SAH. The present study aimed to investigate the mechanisms of MH's protective role in the process of SAH. The present study demonstrated that MH was able to protect against early brain injury in a rat model of SAH. Treating SAH rats with MH reduced the release of reactive oxygen species and prevented activation of apoptotic cascades...
October 2016: Molecular Medicine Reports
Dang Tang, Cheng Wang, Yongjun Gao, Jun Pu, Jiang Long, Wei Xu
Deep hypothermia is known for its organ-preservation properties, which is introduced into surgical operations on the brain and heart, providing both safety in stopping circulation as well as an attractive bloodless operative field. However, the molecular mechanisms have not been clearly identified. This study was undertaken to determine the influence of deep hypothermia on neural apoptosis and the potential mechanism of these effects in PC12 cells following oxygen-glucose deprivation. Deep hypothermia (18°C) was given to PC12 cells while the model of oxygen-glucose deprivation (OGD) induction for 1h...
October 6, 2016: Neuroscience Letters
Jung Ho Lee, Eun Jang Yoon, Jeho Seo, Adriana Kavoussi, Yong Eun Chung, Sung Phil Chung, Incheol Park, Chul Hoon Kim, Je Sung You
Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1...
2016: Molecular Brain
Hannah C Glass, David H Rowitch
Neonatal encephalopathy due to intrapartum events is estimated at 1 to 2 per 1000 live births in high-income countries. Outcomes have improved over the past decade due to implementation of therapeutic hypothermia, the only clinically available neuroprotective strategy for hypoxic-ischemic encephalopathy. Neonatal encephalopathy is the most common condition treated within a neonatal neurocritical care unit. Neonates with encephalopathy benefit from a neurocritical care approach due to prevention of secondary brain injury through attention to basic physiology, earlier recognition and treatment of neurologic complications, consistent management using guidelines and protocols, and use of optimized teams at dedicated referral centers...
September 2016: Clinics in Perinatology
Abbot R Laptook
Birth asphyxia, also termed perinatal hypoxia-ischemia, is a modifiable condition as evidenced by improved outcomes of infants ≥36 weeks' gestation provided hypothermia treatment in randomized trials. Preterm animal models of asphyxia in utero demonstrate that hypothermia can provide short-term neuroprotection for the developing brain, supporting the interest in extending therapeutic hypothermia to preterm infants. This review focuses on the challenge of identifying preterm infants with perinatal asphyxia; the neuropathology of hypoxic-ischemic brain injury across extreme, moderate, and late preterm infants; and patterns of brain injury, use of therapeutic hypothermia, and approach to patient selection for neuroprotective treatments among preterm infants...
September 2016: Clinics in Perinatology
Aldo L Schenone, Aaron Cohen, Gabriel Patarroyo, Logan Harper, XiaoFeng Wang, Mehdi H Shishehbor, Venu Menon, Abhijit Duggal
AIMS OF THE STUDY: We aimed to determine the benefit of an expanded use of TH. We also described the impact of a targeted temperature management on outcomes at discharge. DATA SOURCES: We identified studies by searching MEDLINE, EMBASE and Cochrane Library databases. We included RCTs and observational studiesrestricted to those reporting achieved temperature during TH after OHCA. No other patient, cardiac arrest or hypothermia protocol restrictions were applied...
August 10, 2016: Resuscitation
N Talma, W F Kok, C F de Veij Mestdagh, N C Shanbhag, H R Bouma, R H Henning
BACKGROUND: Targeted temperature management (TTM) is the induced cooling of the entire body or specific organs to help prevent ischemia and reperfusion (I/R) injury, as may occur during major surgery, cardiac resuscitation, traumatic brain injury and stroke. Ischemia and reperfusion induce neuronal damage by mitochondrial dysfunction and oxidative injury, ER stress, neuronal excitotoxicity, and a neuroinflammatory response, which may lead to activation of apoptosis pathways. SCOPE OF REVIEW: The aim of the current review is to discuss TTM targets that convey neuroprotection and to identify potential novel pharmacological intervention strategies for the prevention of cerebral ischemia and reperfusion injury...
November 2016: Biochimica et Biophysica Acta
Hector Lafuente, Maria R Pazos, Antonia Alvarez, Nagat Mohammed, Martín Santos, Maialen Arizti, Francisco J Alvarez, Jose A Martinez-Orgado
Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration...
2016: Frontiers in Neuroscience
Håvard T Garberg, Marianne U Huun, Javier Escobar, Jose Martinez-Orgado, Else-Marit Løberg, Rønnaug Solberg, Ola Didrik Saugstad
BACKGROUND: Cannabidiol (CBD), a non-psychoactive cannabinoid, has shown neuroprotective actions after neonatal hypoxia-ischemia (HI) in animals. We wanted to further explore the effects of CBD, alone and in conjunction with hypothermia, in a piglet model of global HI. METHODS: Fifty-five anesthetized newborn piglets were randomized to either controls (n=7) or HI (n=48) by ventilation with 8% O2 until MABP reached 20 mmHg and/or BE reached -20 mmol/l. After resuscitation piglets were randomized to either: vehicle (VEH), CBD 1mg/kg, VEH+hypothermia (H) or CBD 1mg/kg+H (each n=12)...
July 21, 2016: Pediatric Research
Marlene Fischer, Alois Schiefecker, Peter Lackner, Raimund Helbok, Ronny Beer, Bettina Pfausler, Erich Schmutzhard, Gregor Broessner
Fever is common in neurocritical care patients and is associated with poor outcome. Targeted temperature management (TTM), i.e. therapeutic hypothermia or controlled normothermia, after acute brain injury has been studied as a neuroprotectant for several decades. In contrast to pharmacological agents with specific targets TTM affects multiple pathophysiological mechanisms and is primarily thought to attenuate secondary brain injury. Most promising results have been obtained from experimental studies on cerebral ischemia or traumatic brain injury showing beneficial effects of hypothermia on structural and functional outcome...
July 3, 2016: Current Drug Targets
Liang He, Jun-Mei Xu, Hui Li, Feng Zhong, Zhi Liu, Chang-Qi Li, Ru-Ping Dai
BACKGROUND: Hypothermia reduces immediate paralysis during surgical repair of aortic aneurysms. However, it is unknown what the impact of hypothermia is on delayed paralysis, a serious complication of this type of surgery. METHODS: Sprague-Dawley rats were subjected to occlusion of the descending aorta at different duration under normothermia (38.0±0.5) or hypothermia (33.0±0.5°). Neurologic function was assessed. Motor neuron number, glial activation, and cytokine expression in the spinal cord were examined...
October 1, 2016: International Journal of Cardiology
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