Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke

Wang, G.J; Deng, Holly Y; Maier, Carolina M.; Sun, Guo Hua; Yenari, Midori A.

doi:10.1016/s0306-4522(02)00350-0

Cited by 153 publications

(114 citation statements)

References 58 publications

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“…2,3 Different experimental studies indicated that inflammation contributes significantly to cerebral injury after ischemia 15 and that mild hypothermia in part attenuates this inflammatory response. 13,14 Within ischemic brain tissue, leukocytes contribute to secondary injury releasing reactive oxygen species, activating thrombosis, disrupting the blood-brain barrier, increasing cerebral edema, and plugging the cerebral microvasculature. 15,16 Various studies show that blocking leukocytes infiltration decreases ischemic brain injury and mild hypothermia decreases their accumulation after focal cerebral brain ischemia.…”

Section: Discussionmentioning

confidence: 99%

Different Degrees of Hypothermia After Experimental Stroke

Kollmar

Blank

Han

et al. 2007

Stroke

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Background and Purpose-The neuroprotective role of mild therapeutic hypothermia was established in animal models of cerebral ischemia. Still, several issues, including optimal target temperature, remain unclear. The optimal depth of hypothermia in a rat model of focal cerebral ischemia was investigated. Methods-Eighty-four male Wistar rats (nϭ84) were subjected to filament occlusion of the middle cerebral artery for 90 minutes. Sixty animals were equally split into 6 groups kept at core temperatures of 37°C, 36°C, 35°C, 34°C, 33°C, and 32°C over a period of 4 hours starting 90 minutes after middle cerebral artery occlusion. Twenty-four hours later, after performing a neuroscore, animals were killed and brains examined for infarct size, edema, and invasion of leukocytes.In the second part, 24 animals (8 per group) were kept at 33°C, 34°C, and 37°C for 4 hours, allowed to survive for 5 days, and underwent additional investigation of transferase dUTP nick-end labeling. Results-In the first part, one animal in each treatment group and 2 animals in group 37°C died. The infarct size and edema were smaller for 34°C and 33°C compared with all other groups (PϽ0.05) over 24 hours. These animals also had better functional outcome (PϽ0.05) with an advantage for 34°C versus 33°C (PϽ0.05). Leukocyte count was lower for 34°C and 33°C as compared with the 37°C group. Similar results were obtained in the second part of the study with an advantage for 34°C versus 33°C. Conclusion-Our results suggest that the optimal depth of therapeutic hypothermia in temporary middle cerebral artery occlusion is 34°C.

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Section: Discussionmentioning

confidence: 99%

Different Degrees of Hypothermia After Experimental Stroke

Kollmar

Blank

Han

et al. 2007

Stroke

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“…Intraischemic hypothermia delays or attenuates both ATP depletion (Ibayashi et al, 2000;Sutton et al, 1991;Welsh et al, 1990) and anoxic depolarization (Bart et al, 1998;Nakashima and Todd, 1996;Takeda et al, 2003), it also blocks glutamate release (Busto et al, 1989b;Patel et al, 1994;Winfree et al, 1996), suppresses inflammation (Kawai et al, 2000;Wang et al, 2002), maintains the integrity of the BBB (Dietrich et al, 1990;Huang et al, 1999;Kawanishi, 2003), reduces free radical production , inhibits protein kinase C translocation (Cardell et al, 1991;Shimohata et al, 2007a, b;Tohyama et al, 1998), inhibits matrix metalloproteinase expression (Hamann et al, 2004), and blocks both necrosis and apoptosis. Intraischemic hypothermia also preserves the base-excision repair pathway, which repairs oxidative damage (Luo et al, 2007).…”

Section: The Ostensible Pan-inhibitive Effects Of Hypothermiamentioning

confidence: 99%

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

Zhao

Steinberg

Sapolsky

2007

J Cereb Blood Flow Metab

155

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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“…PMNL accumulation is maximal at 48-72h. Attenuation of the inflammatory response may be one of the mechanisms by which hypothermia reduces ischemic neuronal injury 13,19,20 . Since it has been demonstrated that carr a g eenin is a highly reactive substance with inflammat o ry pro p e rt i e s 2 1 and brain inflammation can be induced with its subarachnoidal injection in brains of mice 2 2 , in this study we aimed to demonstrate that mild hypothermia can have neuroprotective e ffects in brains of rats submitted to inflammatory injury by means of the use of carrageenin.…”

mentioning

confidence: 99%

Mild hypothermia reduces polymorphonuclear leukocytes infiltration in induced brain inflammation

Prandini

Filho

Lapa

et al. 2005

Arq. Neuro-Psiquiatr.

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Over the last 50 years deep hypothermia (23(0) C) has demonstrated to be an excellent neuroprotective agent in cerebral ischemic injury. Mild hypothermia (31-33(0) C) has proven to have the same neuroprotective properties without the detrimental effects of deep hypothermia. Mechanisms of injury that are exaggerated by moderate hyperthermia and ameliorated by hypothermia include, reduction of oxygen radical production, with peroxidase damage to lipids, proteins and DNA, microglial activation and ischemic depolarization, decrease in cerebral metabolic demand for oxygen and reduction of glycerin and excitatory amino acid (EAA) release. Studies have demonstrated that inflammation potentiates cerebral ischemic injury and that hypothermia can reduce neutrophil infiltration in ischemic regions. To further elucidate the mechanisms by which mild hypothermia produces neuroprotection in ischemia by attenuating the inflammatory response, we provoked inflammatory reaction, in brains of rats, dropping a substance that provokes a heavy inflammatory reaction. Two groups of ten animals underwent the same surgical procedure: the skull bone was partially removed, the duramater was opened and an inflammatory substance (5% carrageenin) was topically dropped. The scalp was sutured and, for the group that underwent neuroprotection, an ice bag was placed covering the entire skull surface, in order to maintain the brain temperature between 29,5-31(0) C during 120 minutes. After three days the animals were sacrificed and their brains were examined. The group protected by hypothermia demonstrated a remarkable reduction of polymorphonuclear leukocytes (PMNL) infiltration, indicating that mild hypothermia can have neuroprotective effects by reducing the inflammatory reaction.

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Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke

Cited by 153 publications

References 58 publications

Different Degrees of Hypothermia After Experimental Stroke

Different Degrees of Hypothermia After Experimental Stroke

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

Mild hypothermia reduces polymorphonuclear leukocytes infiltration in induced brain inflammation

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