Mild Intraischemic Hypothermia Reduces Postischemic Hyperperfusion, Delayed Postischemic Hypoperfusion, Blood-Brain Barrier Disruption, Brain Edema, and Neuronal Damage Volume after Temporary Focal Cerebral Ischemia in Rats

Karibe, Hiroyuki; Zarow, Gregory J.; Graham, Steven H.; Weinstein, Philip

doi:10.1038/jcbfm.1994.77

Cited by 224 publications

(90 citation statements)

References 68 publications

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“…Nevertheless, one study reported that moderate hypothermia (301C) significantly reduced CBF using a diffusion-weighted imaging technique (Jiang et al, 1994). Some studies suggest that hypothermia does not affect CBF after reperfusion in focal ischemia (Kawai et al, 2000;Morikawa et al, 1992), whereas others suggest that hypothermia blocks the postischemic hyperperfusion and the delayed, sustained hypoperfusion (Huang et al, 1998;Jiang et al, 1994;Karibe et al, 1994b).…”

Section: Cerebral Blood Flowmentioning

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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Section: Cerebral Blood Flowmentioning

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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“…Early transient postischemic hyperperfusion followed by a period of delayed hypoperfusion is believed to result in reperfusion injuries, with microvascular damage as one of the primary contributing factors (Traupe et al, 1982;Todd et al, 1986;Marchal et al, 1999). Recent studies indicated that possible mechanisms of reperfusion injury include secondary hemodynamic disturbances (Carden and Granger, 2000), the enhancement of inflammatory processes (Karibe et al, 1994), free-radical formation (del Zoppo, 1994;Jiang et al, 1995), disturbance of the mitochondrial function, and vasogenic edema (Chan, 1996) secondary to the breakdown of the blood-brain barrier (Yang and Betz, 1994). Very few studies, however, reported observation of increased cerebral hemodynamics in experimental ischemia after more than 24 hours of reperfusion (Dijkhuizen et al, 1998;van Lookeren Campagne et al, 1999).…”

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confidence: 99%

Late Reversal of Cerebral Perfusion and Water Diffusion after Transient Focal Ischemia in Rats

Wang

Yushmanov

Liachenko

et al. 2002

J Cereb Blood Flow Metab

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Summary: Region-specific cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) of tissue water in the rat brain were quantified by high-field magnetic resonance imaging at 9.4 T in the rat suture occlusion model. Cerebral blood flow and ADC were compared during the short-(4.5 hours) and long-term (up to 6 days) reperfusion after 80 minutes of transient middle cerebral artery occlusion, and correlated with the histology analysis. On occlusion, average CBF fell from ∼100 to less than 50 mL 100 g −1 min −1 in the cortex, and to less than 20 mL 100 g −1 min −1 in the caudate putamen (CP). Corresponding ADC values decreased from (6.98 ± 0.82) × 10 −4 to (5.49 ± 0.54) × 10 −4 mm 2 /s in the cortex, and from (7.16 ± 0.58) × 10 −4 to (4.86 ± 0.62) × 10 −4 mm 2 /s in the CP. On average, CBF recovered to ∼50% of baseline in the first 24 hours of reperfusion. After 2 to 4 days, a strong hyperperfusion in the ipsilateral cortex and CP, up to ∼300 mL 100 g −1 min −1 , was observed. The ADC ratio in the ipsilateral and contralateral CP was also inverted in the late reperfusion period. Histology revealed more severe tissue damage at the late stage of reperfusion than at 4.5 hours. Significant reversal of CBF and ADC during the late reperfusion period may reflect the impairment of autoregulation in the ischemic regions. Vascular factors may play an important role in the infarct development after 80-minute focal ischemia.

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“…The pathophysiological mechanisms involved include stabilization of the blood-brain barrier, [1][2][3] downregulation of cerebral metabolism, 4 and decrease of excitatory amino acids. 5,6 Additionally, preliminary clinical findings suggested that moderate hypothermia may influence mortality in patients with malignant middle cerebral artery infarction.…”

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confidence: 99%

Endovascular Cooling for Moderate Hypothermia in Patients With Acute Stroke: First Results of a Novel Approach

Georgiadis

Schwarz²,

Kollmar³

et al. 2001

Stroke

232

122

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Background and Purpose-We undertook this study to evaluate the feasibility of inducing and maintaining moderate hypothermia with the use of endovascular rather than surface cooling. Methods-Six patients with severe acute ischemic stroke were treated with moderate hypothermia. This was induced and maintained by circulating temperature-adjusted normal saline in a closed-loop system entailing 3 balloons located near the tip of a central line, which dwelled in the inferior vena cava. Results-The meanϮSD initial temperature of the patients was 37Ϯ1°C (range, 35.5°C to 38.4°C). The pace of cooling was 1.4Ϯ0.6°C/h , and target temperature was reached after 3Ϯ1 hours (range, 2 to 4.5 hours). During hypothermia, the maximal temperature observed was 33.4°C, and the minimal temperature was 32.2°C. Temperature deviations Ͼ0.2°C or Ͼ0.3°C were observed during 21% or 10% of the hours under hypothermia, respectively. Singultus was the only device-related complication encountered. Pulmonary infection, arterial hypotension, bradycardia, arrhythmia, and thrombocytopenia were the most common side effects. Key Words: stroke, acute Ⅲ stroke management T he neuroprotective properties of moderate hypothermia in acute ischemic stroke were demonstrated in several experimental models. The pathophysiological mechanisms involved include stabilization of the blood-brain barrier, 1-3 downregulation of cerebral metabolism, 4 and decrease of excitatory amino acids. 5,6 Additionally, preliminary clinical findings suggested that moderate hypothermia may influence mortality in patients with malignant middle cerebral artery infarction. 7,8 Currently, hypothermia is being induced by surface cooling with the use of cooling blankets, alcohol applied to exposed skin, or ice bags to groin, axilla, and neck. This approach, however, requires intensive effort from the medical and nursing staff for induction as well as maintenance of the target temperature. Conclusions-InductionRecently, an alternative approach based on intravenous cooling was proposed. A custom-built central line is advanced in the inferior vena cava. Normal saline is circulated through 3 balloons located near the tip of this line in a closed-loop system. Temperature regulation is achieved by adjusting the temperature of the circulating saline by a temperature-managing device.We undertook this study to evaluate the potential of intravenous cooling for induction as well as maintenance of moderate hypothermia (33°C). Subjects and MethodsA total of 6 patients (5 men and 1 woman aged 64.5Ϯ8.4 years) with an ischemic infarction involving at least two thirds of the territory of the left (nϭ5) or right (nϭ1) middle cerebral artery were treated with moderate hypothermia according to our institutional protocol. All patients were sedated with midazolam at the time of the study; fentanyl was used for analgesia and atracurium for neuromuscular blockade. Alpha-stat was used for acid-base management. Patients lay in the 30°head-up position and were ventilated with a volumecontrolled, pressure-regulated...

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Mild Intraischemic Hypothermia Reduces Postischemic Hyperperfusion, Delayed Postischemic Hypoperfusion, Blood-Brain Barrier Disruption, Brain Edema, and Neuronal Damage Volume after Temporary Focal Cerebral Ischemia in Rats

Cited by 224 publications

References 68 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

Late Reversal of Cerebral Perfusion and Water Diffusion after Transient Focal Ischemia in Rats

Endovascular Cooling for Moderate Hypothermia in Patients With Acute Stroke: First Results of a Novel Approach

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