Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: a time-course study

Abstract

The effect of hypothermia on neuronal injury following permanent middle cerebral artery (MCA) occlusion in the rat was examined. Moderate hypothermia (body temperature 24 degrees C) was induced before MCA occlusion (0-minute delay group) in six rats, at 30 minutes in eight rats, and at 1 (seven rats), 2 (seven rats), and 3 (nine rats) hours after occlusion. The rats were kept at a 24 degrees C body temperature for 1 hour, then allowed to rewarm over 90 minutes. The animals were sacrificed 24 hours after MCA occlusion, and infarction was visualized by staining of coronal sections with 2,3,5-triphenyltetrazolium chloride. Infarct volumes were compared to matched normothermic control rats (body temperature 36 degrees C). Additional groups of 0-minute delay hypothermic (10 rats) and control animals (nine rats) were sacrificed 72 hours after MCA occlusion to examine the effects of prolonged survival. A significant reduction in the percentage of infarcted right hemisphere was seen in the animals sacrificed after 24 hours with 0-minute, 30-minute, and 1-hour delays in inducing hypothermia (mean +/- standard error of the mean: 2.2% +/- 0.7%, 4.4% +/- 0.9%, and 3.6% +/- 1.1%, respectively) as compared to normothermic control rats (10.8% +/- 1.5%, p less than 0.01 by Student's t-test). In the 2- and 3-hour delay groups, the percentage of infarcted right hemisphere was 17.1% +/- 2.4% and 12.0% +/- 2.7%, respectively, and no decrease in infarct volume was observed. The 0-minute delay hypothermia group sacrificed after 72 hours also displayed a significant reduction in right hemisphere infarct compared to their respective controls (4.8% vs. 11.7%, p less than 0.05). These findings indicate that, in the setting of permanent MCA occlusion, hypothermia markedly decreases brain injury even when its induction is delayed for up to 1 hour after the onset of ischemia. Ischemic damage does not appear to be merely retarded but permanently averted.

Hypothermic Protection in Rat Focal Ischemia Models: Strain Differences and Relevance to “Reperfusion Injury”

“…5 provide confirmation that infarct volume is significantly reduced by 2-hour hypothermia in this strain, whereas identical intervention in the SHR is ineffective. The present results also indicate that moderate cooling is as protective as profound (24°C) cooling (Baker et al, 1992). Clearly, temperature-sensitive mechanisms operate during a substantial postocclusion window, with or without overt reperfusion, that determine the extent of subsequent injury expansion in Wistar rats.…”

Transient Cooling during Early Reperfusion Attenuates Delayed Edema and Infarct Progression in the Spontaneously Hypertensive Rat. Distribution and Time Course of Regional Brain Temperature Change in a Model of Postischemic Hypothermic Protection

“…Furthermore, as typically implemented such models also have the potential to produce unrecognized vascular trauma and a resultant prothrombotic state, which would extend the effective duration of cerebral blood flow reduction and thereby increase sensitivity to prolonged, moderate cooling. In addition, filament models typically use strains that exhibit sufficient collateral perfusion to tolerate prolonged obstruction of the internal carotid artery, and brains of such animals can be protected by transient hypothermia even in the absence of overt reperfusion (Baker et al, 1992;Kader et al, 1992;Morikawa et al, 1992;Ren et al, 2004;Yanamoto et al, 2001), provided that cooling is initiated soon enough after occlusion (Baker et al, 1992). It should also be noted that occasional studies of moderate postischemic cooling after filament occlusions have been negative (Huang et al, 1998), including the finding of delayed lesion evolution without significant long-term protection (Inamasu et al, 2000).…”

“…As in other strains, moderate intraischemic hypothermia is clearly protective during transient middle cerebral artery (MCA) occlusion in SHR (Aronowski et al, 1994;Barone et al, 1997;Ridenour et al, 1992). Cooling in the absence of reperfusion has been generally found not to be protective (Ren et al, 2004;Ridenour et al, 1992), in contrast to its beneficial effects in Wistar rats that maintain better collateral perfusion during occlusion (Baker et al, 1992;Kader et al, 1992;Ren et al, 2004). The one exception employed profound 241C cooling of SHR during the initial hour of permanent occlusion of the MCA alone (Onesti et al, 1991), which would have allowed appreciable residual perfusion even in this strain.…”

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

“…Delayed induction of hypothermia -after the ischemic or traumatic insult -provided brain protection in various experimental models [16], [35], [39], [40] and [41]. Reductions of only 2-4 °C, which produce relatively small decreases of brain metabolism, also have protective effects.…”