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therapeutic hypothermia and stroke

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
Jin Hwan Lee, Zheng Z Wei, Wenyuan Cao, Soonmi Won, Xiaohuan Gu, Megan Winter, Thomas A Dix, Ling Wei, Shan Ping Yu
Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models...
September 19, 2016: Neurobiology of Disease
Satoko Tomita Ide, Ryoji Ide, Jacopo P Mortola
In embryos, cooling and hypoxia cause a decrease in oxygen consumption ( [Formula: see text] ); we asked what was the relative contribution of heart rate (HR) and of the 'not-HR' factor (the product of stroke volume and arterial-venous O2 difference) to the drop in [Formula: see text] . Data of HR (with subcutaneous electrodes) and [Formula: see text] (by an open-flow methodology) were collected simultaneously on chicken embryos close to end-incubation. Over the last four days of incubation (E16-E20) differences in HR contributed about 30% of the differences in resting [Formula: see text] among embryos...
August 30, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
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
Michael Qize Jiang, Ying-Ying Zhao, Wenyuan Cao, Zheng Zachory Wei, Xiaohuan Gu, Ling Wei, Shan Ping Yu
Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain. Adult mice were subjected to focal cerebral ischemia induced by permanent occlusion of distal branches of the middle cerebral artery (MCA) plus transient ligations of bilateral common carotid artery (CCA)...
August 11, 2016: Brain Pathology
Han-Yeong Jeong, Jun-Young Chang, Kyu Sun Yum, Jeong-Ho Hong, Jin-Heon Jeong, Min-Ju Yeo, Hee-Joon Bae, Moon-Ku Han, Kiwon Lee
BACKGROUND AND PURPOSE: The use of decompressive hemicraniectomy (DHC) for the treatment of malignant cerebral edema can decrease mortality rates. However, this benefit is not sufficient to justify its use in elderly patients. We investigated the effects of therapeutic hypothermia (TH) on safety, feasibility, and functional outcomes in elderly patients with malignant middle cerebral artery (MCA) infarcts. METHODS: Elderly patients 60 years of age and older with infarcts affecting more than two-thirds of the MCA territory were included...
September 2016: Journal of Stroke
Domenico Tupone, Justin S Cetas, Shaun F Morrison
The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Pharmacological manipulation of central autonomic thermoregulatory circuits could represent a potential target for the induction of a hypothermic state. Here we present a brief description of the CNS thermoregulatory centers and how the manipulation of these circuits can be useful in the treatment of pathological conditions such as stroke or brain hemorrhage...
April 2016: Nihon Shinkei Seishin Yakurigaku Zasshi, Japanese Journal of Psychopharmacology
Ana C Klahr, Colby A Nadeau, Frederick Colbourne
Extensive animal research facilitated the clinical translation of therapeutic hypothermia for cardiac arrest in adults and hypoxic-ischemic injury in infants. Similarly, clinical interest in hypothermia for other brain injuries, such as stroke, has been greatly supported by positive findings in preclinical work. The reliability, validity, and utility of animal models, among many research practices (blinding, randomization, etc.), are key to successful clinical translation. Here, we review methods used to induce and maintain hypothermia in animal models...
June 21, 2016: Therapeutic Hypothermia and Temperature Management
Rizwan A Tahir, Aqueel H Pabaney
BACKGROUND: Ischemic stroke is the fifth leading cause of death in the US. Clinical techniques aimed at helping to reduce the morbidity associated with stroke have been studied extensively, including therapeutic hypothermia. In this study, the authors review the literature regarding the role of therapeutic hypothermia in ischemic stroke to appreciate the evolution of hypothermia technology over several decades and to critically analyze several early clinical studies to validate its use in ischemic stroke...
2016: Surgical Neurology International
Thomas L Merrill, Jennifer E Mitchell, Denise R Merrill
Recent revascularization success for ischemic stroke patients using stentrievers has created a new opportunity for therapeutic hypothermia. By using short term localized tissue cooling interventional catheters can be used to reduce reperfusion injury and improve neurological outcomes. Using experimental testing and a well-established heat exchanger design approach, the ɛ-NTU method, this paper examines the cooling performance of commercially available catheters as function of four practical parameters: (1) infusion flow rate, (2) catheter location in the body, (3) catheter configuration and design, and (4) cooling approach...
August 2016: Medical Engineering & Physics
Jin Hwan Lee, Ling Wei, Xiaohuan Gu, Soonmi Won, Zheng Zachory Wei, Thomas A Dix, Shan Ping Yu
BACKGROUND AND PURPOSE: Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke. METHODS: Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament...
July 2016: Stroke; a Journal of Cerebral Circulation
Francesco Pisani, Carlotta Spagnoli
Due to the increasing number of surviving preterm newborns and to the recognition of therapeutic hypothermia as the current gold standard in newborns with hypoxic-ischaemic encephalopathy, there has been a growing interest in the implementation of brain monitoring tools in newborns at high risk for neurological disorders.Among the most frequent neurological conditions and presentations in the neonatal period, neonatal seizures and neonatal status epilepticus, paroxysmal non-epileptic motor phenomena, hypoxic-ischaemic encephalopathy, white matter injury of prematurity and stroke require specific approaches to diagnosis...
2016: Italian Journal of Pediatrics
Zhou Wu, Shu-Zhen Zhu, Ya-Fang Hu, Yong Gu, Sheng-Nan Wang, Zhen-Zhou Lin, Zuo-Shan Xie, Su-Yue Pan
In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors...
July 15, 2016: Brain Research
Jessica A Lamb, Padmesh S Rajput, Patrick D Lyden
BACKGROUND: Hypothermia is the most potent protective therapy available for cerebral ischemia. In experimental models, cooling the brain even a single degree Celsius alters outcome after global and focal ischemia. Difficulties translating therapeutic hypothermia to patients with stroke or after cardiac arrest include: uncertainty as to the optimal treatment duration; best target-depth temperature; and longest time delay after which therapeutic hypothermia won't benefit. Recent results from human clinical trials suggest that cooling with surface methods provides insufficient cooling speed or control over target temperature...
July 15, 2016: Journal of Neuroscience Methods
Oana M Dumitrascu, Jessica Lamb, Patrick D Lyden
Therapeutic hypothermia is the most potent neuroprotectant for experimental cerebral ischemia, illustrated in a 2007 meta-analysis published in this journal. To address recent therapeutic nihilism, we systematically reviewed recent experimental literature. Quality scoring showed considerable improvement in study design. Using several outcome measures in a variety of models and species, therapeutic hypothermia was protective compared with normothermia, with powerful and statistically significant normalized treatment effect sizes, in 60 papers comprising 216 comparisons...
July 2016: Journal of Cerebral Blood Flow and Metabolism
Lipeng Cai, Alexa Thibodeau, Changya Peng, Xunming Ji, Radhika Rastogi, Ruiqiang Xin, Sunpreet Singh, Xiaokun Geng, Jose A Rafols, Yuchuan Ding
Pyruvate dehydrogenase complex (PDH) is a brain mitochondrial matrix enzyme. PDH impairment after stroke is particularly devastating given PDH's critical role in the link between anaerobic and aerobic metabolism. This study evaluates the restoration of oxidative metabolism and energy regulation with a therapeutic combination of normobaric oxygen (NBO) plus either therapeutic hypothermia (TH) or ethanol. Sprague-Dawley rats were subjected to middle cerebral artery occlusion with an autologous embolus. One hour after occlusion, tissue-type plasminogen activator (t-PA) was administered alone or with NBO (60%), EtOH (1...
August 2016: Journal of Neuroscience Research
Brian Forreider, David Pozivilko, Qingwen Kawaji, Xiaokun Geng, Yuchuan Ding
Many mammalian species naturally undergo hibernation, a process that is associated with drastic changes in metabolism and systemic physiology. Their ability to retain an undamaged central nervous system during severely reduced cerebral blood flow has been studied for possible therapeutic application in human ischemic stroke. By inducing a less extreme 'hibernation-like' state, it has been hypothesized that similar neuroprotective effects reduce ischemia-mediated tissue damage in stroke patients. This manuscript includes reviews and evaluations of: (1) true hibernation, (2) hibernation-like state and its neuroprotective characteristics, (3) the preclinical and clinical methods for induction of artificial hibernation (i...
March 7, 2016: Progress in Neurobiology
Mark S Wainwright, Gregory Hansen, Juan Piantino
PURPOSE OF REVIEW: Approximately one in five children admitted to a pediatric ICU have a new central nervous system injury or a neurological complication of their critical illness. The spectrum of neurologic insults in children is diverse and clinical practice is largely empirical, as few randomized, controlled trials have been reported. This lack of data poses a substantial challenge to the practice of pediatric neurocritical care (PNCC). PNCC has emerged as a novel subspecialty, and its presence is expanding within tertiary care centers...
April 2016: Current Opinion in Critical Care
Lipeng Cai, James Stevenson, Xiaokun Geng, Changya Peng, Xunming Ji, Ruiqiang Xin, Radhika Rastogi, Christopher Sy, Jose A Rafols, Yuchuan Ding
In a thromboembolic stroke model after reperfusion by recombinant tissue plasminogen activator (rt-PA), we aimed to determine whether therapeutic hypothermia (TH) and ethanol (EtOH) in combination with low concentration (60 %) of normobaric oxygen (NBO) enhanced neuroprotection, as compared to using each of these agents alone. We further aimed to elucidate a potential role of the NADPH oxidase (NOX), phosphorylated protein kinase B (Akt), and protein kinase C-δ (PKC-δ) pathway in oxidative stress and neuroprotection...
January 28, 2016: Molecular Neurobiology
L Cai, J Stevenson, C Peng, R Xin, R Rastogi, K Liu, X Geng, Z Gao, X Ji, J A Rafols, Z Ji, Y Ding
BACKGROUND AND PURPOSE: Normobaric oxygen (NBO), ethanol (EtOH), and therapeutic hypothermia (TH) delivered alone or in combination have neuroprotective properties after acute stroke. We used an autologous thromboembolic rat stroke model to assess the additive effects of these treatments for reducing the deleterious effects of hyperglycolysis post-stroke in which reperfusion is induced with recombinant tissue plasminogen activator (rt-PA). METHODS: Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion with an autologous embolus...
March 24, 2016: Neuroscience
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