Effects of Hypothermia on Excitatory Amino Acids and Metabolism in Stroke Patients

Berger, Christian; Schäbitz, Wolf‐Rüdiger; Georgiadis, Dimitrios; Steiner, Thorsten; Aschoff, A.; Schwab, Stefan

doi:10.1161/hs0102.100878

Cited by 122 publications

(80 citation statements)

References 40 publications

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“…It has been reported that mild hypothermia completely blocks (Busto et al, 1989b;Li et al, 1999;MartinezTica and Zornow, 2000;Patel et al, 1994), partially blocks Winfree et al, 1996;Yamamoto et al, 1999), merely delays (Asai et al, 2000(Asai et al, , 1998, or does not inhibit an increase in [Glu] e after cerebral ischemia (Berger et al, 1998;Zhao et al, 1997). Furthermore, the effect of hypothermia on [Glu] e depends on the brain area, ischemic severity, and animal age (Berger et al, 2002;Lo et al, 1993;Van Hemelrijck et al, 2003). It is not clear why there is such variation across studies concerning [Glu] e .…”

Section: Glutamate Releasementioning

confidence: 99%

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

Zhao

Steinberg

Sapolsky

2007

J Cereb Blood Flow Metab

156

135

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Mild or moderate hypothermia is generally thought to block all changes in signaling events that are detrimental to ischemic brain, including ATP depletion, glutamate release, Ca 2 + mobilization, anoxic depolarization, free radical generation, inflammation, blood-brain barrier permeability, necrotic, and apoptotic pathways. However, the effects and mechanisms of hypothermia are, in fact, variable. We emphasize that, even in the laboratory, hypothermic protection is limited. In certain models of permanent focal ischemia, hypothermia may not protect at all. In cases where hypothermia reduces infarct, some studies have overemphasized its ability to maintain cerebral blood flow and ATP levels, and to prevent anoxic depolarization, glutamate release during ischemia. Instead, hypothermia may protect against ischemia by regulating cascades that occur after reperfusion, including blood-brain barrier permeability and the changes in gene and protein expressions associated with necrotic and apoptotic pathways. Hypothermia not only blocks multiple damaging cascades after stroke, but also selectively upregulates some protective genes. However, most of these mechanisms are addressed in models with intraischemic hypothermia; much less information is available in models with postischemic hypothermia. Moreover, although it has been confirmed that mild hypothermia is clinically feasible for acute focal stroke treatment, no definite beneficial effect has been reported yet. This lack of clinical protection may result from suboptimal criteria for patient entrance into clinical trials. To facilitate clinical translation, future efforts in the laboratory should focus more on the protective mechanisms of postischemic hypothermia, as well as on the effects of sex, age and rewarming during reperfusion on hypothermic protection.

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Section: Glutamate Releasementioning

confidence: 99%

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

Zhao

Steinberg

Sapolsky

2007

J Cereb Blood Flow Metab

156

135

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“…For example, it may have a 'membrane-stabilizing' effect, improving the altered permeability to ions [44]. Hypothermia also prevents the extracellular increase of brain excitatory neurotransmitters in brain ischemia [45], [46], [47], [48], [49], [50] and [51] and neurotrauma [20] and [52]. The extracellular levels of glutamate correlate with the formation of free radicals [52] and [53], which can influence signalling pathways or cause direct damage of cellular components.…”

Section: Introductionmentioning

confidence: 99%

Keeping cool in acute liver failure: Rationale for the use of mild hypothermia

Vaquero

Rose

Butterworth

2005

Journal of Hepatology

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Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.

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“…Знижена температура тіла має підтримуватися упродовж тривалого періоду після інсульту для досягнення довгочасного не-йропротекторного ефекту [1,14,15,21]. Проте обґрунтовані стандартні параметри терапев-тичної гіпотермії на сьогодні відсутні [20].…”

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“…Методом мікродіалізу Berger показав, що незначна гіпотермія (33 °C) спричиняє зниження концентрації позаклітинного глутамату, пірувату, лактату та гліцеролу в ділянці пенумбри, проте не впливає на ділянку ядра інфаркту [1].…”

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Glutamate transport in rat cerebral hemisphere nerve terminals under conditions of deep and profound hypothermia

Pastukhov¹,

Krisanova²,

Borisova³

2017

Bìol. Tvarin

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Effects of Hypothermia on Excitatory Amino Acids and Metabolism in Stroke Patients

Abstract: Background and Purpose-The objective of this study was to assess the effect of therapeutic moderate hypothermia on excitatory amino acids and metabolism by applying cerebral microdialysis in patients suffering from space-occupying middle cerebral artery infarction. Methods-This

Cited by 122 publications

References 40 publications

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

Keeping cool in acute liver failure: Rationale for the use of mild hypothermia

Glutamate transport in rat cerebral hemisphere nerve terminals under conditions of deep and profound hypothermia

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