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

Abstract

The temperature threshold for protection by brief postischemic cooling was evaluated in a model of transient focal ischemia in the Spontaneously Hypertensive Rat, using an array of epidural probes to monitor regional brain temperatures. Rats were subjected to 90 mins tandem occlusion of the right middle cerebral artery (MCA) and common carotid artery. Systemic cooling to 321C was initiated 5 mins before recirculation, with simultaneous brain cooling to temperatures ranging from 281C to 321C within the MCA territory by means of a temperature-controlled saline drip. Rewarming was initiated at 2 h recirculation and was complete within 30 mins. Tissue damage and edema volume showed clear temperature-dependent reductions when evaluated at 3 days survival, with no protection evident in the group at 321C but progressive effects on both parameters after deeper cooling. A particularly striking effect was the essentially complete elimination of edema progression between 1 and 3 days. Temperature at distal sites within the MCA territory better predicted reductions in lesion volume, indicating that protection required effective cooling of the penumbral regions destined to be spared. These results show that even brief cooling can be highly protective when initiated at the time of recirculation after focal ischemia, but indicate a substantially lower temperature threshold for hypothermic protection than has been reported for other strains, occlusion methods, and cooling durations.

Temporal Thresholds for Infarction and Hypothermic Protection in Long-Evans Rats

“…The N-methyl-D-aspartate receptor antagonist, MK-801, which globally increases CBF, 24,25 demonstrates efficacy with a single early administration in a model of permanent MCA occlusion in Fischer-344 rats 26 but not in spontaneously hypertensive rats. 26,27 Conversely, results in the proximal-occlusion model essentially confirm previous demonstrations of experimentally accessible reperfusion injury with a very short temporal window, based on the protective efficacy of acute cooling initiated before reperfusion 1,9 (group F in Figure 4), although protection remained just short of stringent statistical significance in this limited study. Comparable injury mechanisms may operate for a more protracted time course during permanent occlusions under conditions of robust collateral perfusion.…”

“…When applied during early reperfusion, this intervention is highly protective after transient focal ischemia, with persistent protection verified through 1 week. 9 …”

“…1,9 Cooling was achieved by resetting the control point for systemic temperature and packing the animals in ice to reach 32Ϯ0.2°C with a time course of 20 to 30 minutes. At the same time, the saline superfusate temperature setpoint was adjusted to 27°C, requiring Ϸ10 minutes to reach a mean temperature of 26.8Ϯ0.3°C in the saline pool overlying the exposed MCA.…”

Epidurale Kühlung

“…[22]. Eine Vielzahl an Studien zeigt auf indirektem Weg anhand von po sitiven protektiven Effekten im gekühlten Gewebe, das es tatsächlich zu einer Hypo thermie im Zielgewebe kommt [23,24,25].…”

Review: Therapeutic applications of hypothermia in cerebral ischaemia

“…Two laboratory studies using Spargue Dawley [SD; Huh et al 2000] or spontaneously hypertensive rats [SHR; Kurasako et al 2007], but similar levels and durations of marked hypothermia (27-28 C/2-3 h) induced immediately after transient focal ischaemia produced a positive neuroprotective outcome or a trend towards neuroprotection. In addition, to the strain of rat used in the two studies, the shorter period of ischaemia in the positive SHR rat study (90 min) compared to the negative SD rat study (120 min) may have accounted for these results.…”