Spontaneous cerebral hypothermia diminishes focal infarction in rat brain.

Moyer, Donald J.; Welsh, Frank A.; Zager, Eric L.

doi:10.1161/01.str.23.12.1812

Cited by 80 publications

(21 citation statements)

References 27 publications

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“…These findings have been supported by other laboratories. Denes et al [30] reported that LPS compromised survival and increased brain edema but not infarct size as assessed by crystal-violet staining; Moyer et al [31] reported hypothermia during occlusion diminishes cerebral infarction in rats. Several groups have reported that NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F)quinoxaline), an α-amino-3-hydroxy-5-methyl-4-isoxazole propionate antagonist, provides robust protection against neuronal loss in experimental stroke models [32][33][34][35].…”

Section: Aging and Disease • Volume 7 Number 3 June 2016 11mentioning

confidence: 99%

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Hu¹,

Doll²,

Sun³

et al. 2016

Aging and disease

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Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients -targeting endothelial mitochondria may be a clinically useful approach for stroke therapy.

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Section: Aging and Disease • Volume 7 Number 3 June 2016 11mentioning

confidence: 99%

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Hu¹,

Doll²,

Sun³

et al. 2016

Aging and disease

View full text Add to dashboard Cite

show abstract

“…Intraischemic hypothermia is most effective in transient ischemia or 'reperfusion' models (Busto et al, 1989a;Carroll and Beek, 1992;Colbourne and Corbett, 1995); the effects of intraischemic hypothermia in permanent ischemia models are far less uniform (Baker et al, 1991;Kader et al, 1992;Kozlowski et al, 1997;Lo et al, 1993;Morikawa et al, 1992;Moyer et al, 1992;Ridenour et al, 1992;Zhao et al, 2007) . In addition, it will be most meaningful clinically if hypothermia protects when applied postischemically; however, therapeutic time windows for postischemic hypothermia are limited.…”

Section: Hypothermia Does Not Always Attenuate Stroke Even In the Labmentioning

confidence: 99%

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

Zhao

Steinberg

Sapolsky

2007

J Cereb Blood Flow Metab

153

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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“…As little as 1 hour of moderate to deep hypothermia delayed for 1 hour after ischemia onset was beneficial in some models 16,18 but not in others. 19,25 There is no experimental evidence that brief deep hypothermia ameliorates infarct volume if initiated later than 60 minutes after onset of ischemia in permanent occlusion models. 16 Studies in other cerebral ischemia models indicate that hypothermia can protect even if cooling is delayed by several hours, provided the duration of cooling is prolonged.…”

Section: Mild Hypothermia In Models Of Pmcaomentioning

confidence: 99%

Therapeutic Hypothermia for Acute Ischemic Stroke

Krieger

Yenari

2004

Stroke

192

125

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Background and Purpose-The significance of brain temperature to outcome in cerebral ischemia is recognized.Numerous variations of depth, duration, and delay of cooling have been studied in animal models. It is important to become familiar with these studies to design appropriate clinical trials. With that in mind, a critical review of the pertinent literature is presented, taking into consideration potential limitations in translating such laboratory work to the clinical level. Methods-Hypothermia is an especially robust neuroprotectant in the laboratory and has been shown to alter many of the damaging effects of cerebral ischemia. Most laboratory research on therapeutic cooling in cerebral ischemia has been conducted in rodent models of temporary and permanent middle cerebral artery occlusion and report the effects of mild or moderate hypothermia arranged during or after ischemia. Results-Intraischemic cooling vastly reduces infarct size in most occlusion models. Tissue salvage with delayed onset of cooling is less dramatic but is commonly observed when cooling is begun within 60 minutes of stroke onset in permanent and 180 minutes of stroke onset in temporary occlusion models. Prolonged postischemic cooling further enhances efficacy. Conclusions-Laboratory studies have shown that intraischemic hypothermia is more protective than postischemic hypothermia and more benefit is conferred with temporary occlusion than permanent occlusion models. The efficacy of postischemic hypothermia is critically dependent on the duration and depth of hypothermia and its timing relative to ischemia.

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Spontaneous cerebral hypothermia diminishes focal infarction in rat brain.

Cited by 80 publications

References 27 publications

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

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

Therapeutic Hypothermia for Acute Ischemic Stroke

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