Different Degrees of Hypothermia After Experimental Stroke

Abstract

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.

Effects of Global Cerebral Ischemia in the Pregnant Rat

“…29 It is also one of the few promising treatments for alleviating such damage in humans, 12,13 but we saw no such neuroprotective effect here. We should note that the neuroprotective effects associated with hypothermia are maximized under certain very specific conditions, such as with particular temperatures 30 or timing and duration of application. 31 Thus, generalized body-temperature attenuation or an alteration of the usual set point may not have the same neuroprotective effects.…”

Hypothermia in Stroke Therapy: Systemic versus Local Application

“…While there is no exact consensus on the optimal degree of cooling, several studies have found cooling at 33°C to be most efective [7][8][9][10]. The vast majority of investigations on the topic feature a mild to moderate degree of cooling, with very few venturing into moderate-deep to deep hypothermia ( Table 1).…”

Defeating Normal Thermoregulatory Defenses

“…It is most likely that other actions (eg, decreased release of excitatory amino acids, reduced inflammation) explain the protective action of hypothermia. 2 It appears that much of the total benefit from moderate hypothermia occurs within the first couple of degrees, 3 thereby making hypothermia an attractive therapeutic option because the benefits may well exceed the risks.…”