Rapid and long-lasting tolerance to clomethiazole-induced hypothermia in the rat

Visser, Sandra A.G.; Pozarek, Susanna; Martinsson, Svante; Forsberg, Tomas; Ross, Svante B.; Gabrielsson, Johan

doi:10.1016/j.ejphar.2005.02.036

Cited by 12 publications

(5 citation statements)

References 37 publications

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“…GABA‐ergic activation reduces the metabolic respiratory rate, preserving glucose and reducing acidosis, and facilitates local cerebral blood flow . GABA receptor agonists can induce hypothermia, which is also regarded as a neuroprotective condition for acute stroke . To test these theories, a multicenter, randomized, stratified, double‐blind, placebo‐controlled clinical human trial was conducted.…”

Section: Discussionmentioning

confidence: 99%

Benzodiazepine use and risk of stroke: A retrospective population‐based cohort study

Huang

Muo²,

Chang³

et al. 2013

Psychiatry Clin Neurosci

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Aim:The aim of this study was to investigate the possible association between benzodiazepine (BZD) use and risk of incident stroke by utilizing data from 2000 to 2003 from the National Health Insurance system of Taiwan.Methods: Study subjects consisted of 38 671 patients with new BZD use and 38 663 people without BZD use who were frequency-matched for age, sex and baseline comorbidity with BZD users. All subjects had no history of stroke. Each study patient's case was followed until a new diagnosis of stroke was made or until the patient was censored by loss to follow up, death, or termination of insurance. The study lasted until the end of 2009. A Cox proportional hazards regression model was used to estimate the incidences and hazard ratios (HR) of stroke.Results: The HR of hemorrhagic stroke was significantly lower in the BZD group when compared with the non-BZD group. For patients aged 20-39 years, the HR of ischemic stroke was significantly higher in the BZD group when compared with the non-BZD group. Compared to the non-BZD group, patients with a lower annual dosage (<1 g) or duration (<30 days) of BZD use had a lower risk of stroke in the elder group (P < 0.0001) and patients with a higher annual dosage (≥ 4 g) or duration (≥ 95 days) of BZD use had a higher risk of stroke in all age groups (P < 0.0001). Conclusions:Our findings may suggest neuroprotection under lower-dosage BZD use and neurotoxicity under higher-dosage BZD use.

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Section: Discussionmentioning

confidence: 99%

Benzodiazepine use and risk of stroke: A retrospective population‐based cohort study

Huang

Muo²,

Chang³

et al. 2013

Psychiatry Clin Neurosci

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“…It would be foolish to simply constrain animal temperature to the normal range during experiments as the induction of hypothermia, or other changes that lead to it, might be the mechanism of action of a new drug. A number of candidate pharmacological neuroprotectants such as the AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole- propionate) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione) (NBQX) (Nurse and Corbett, 1996) and the sedative clomethiazole (Visser et al , 2005) probably involve hypothermic effects in their mechanism of action, whereas others such as Mg 2+ (Campbell et al , 2008) and tacrolimus (FK506) (Nito et al , 2004) are reported to have their effects enhanced by even mild hypothermia. Even the prototypical antiexcitotoxic dizocilpine (MK-801) alters body temperature and can have its effects masked by concomitant hyperthermia (Memezawa et al , 1995).…”

Section: Experimentally Controllable Physiologic Variables That Affecmentioning

confidence: 99%

Different Strokes for Different Folks: The Rich Diversity of Animal Models of Focal Cerebral Ischemia

Howells

Porritt

Rewell

et al. 2010

J Cereb Blood Flow Metab

270

231

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No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research.

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“…The use of unwarmed anesthetic gases exacerbates this problem (Haskins and Patz, 1980). Cooling can be profoundly neuroprotective (van der Worp et al, 2007), and the mechanism of action of a putative neuroprotectant itself may be related to a hypothermic process, as is thought for clomethiazole (Visser et al, 2005). In humans, however, hyperthermia is common following ICH and duration of fever is an independent prognostic indicator (Schwarz et al, 2000).…”

Section: Minimizing Excess Inflammationmentioning

confidence: 99%

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

J Cereb Blood Flow Metab

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Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes, yet treatments are mainly limited to supportive management, and surgery remains controversial. Despite significant advances in our understanding of ICH pathophysiology, we still lack preclinical models that accurately replicate the underlying mechanisms of injury. Current experimental ICH models (including autologous blood and collagenase injection) simulate different aspects of ICH-mediated injury but lack some features of the clinical condition. Newly developed models, notably hypertension-and oral anticoagulant therapy-associated ICH models, offer added benefits but further study is needed to fully validate them. Here, we describe and discuss current approaches to experimental ICH, with suggestions for changes in how this condition is studied in the laboratory. Although advances in imaging over the past few decades have allowed greater insight into clinical ICH, there remains an important role for experimental models in furthering our understanding of the basic pathophysiologic processes underlying ICH, provided limitations of animal models are borne in mind. Owing to differences in existing models and the failed translation of benefits in experimental ICH to clinical practice, putative neuroprotectants should be trialed in multiple models using both histological and functional outcomes until a more accurate model of ICH is developed.

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Rapid and long-lasting tolerance to clomethiazole-induced hypothermia in the rat

Cited by 12 publications

References 37 publications

Benzodiazepine use and risk of stroke: A retrospective population‐based cohort study

Benzodiazepine use and risk of stroke: A retrospective population‐based cohort study

Different Strokes for Different Folks: The Rich Diversity of Animal Models of Focal Cerebral Ischemia

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

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