Neuroprotective Effect of Delayed Moderate Hypothermia After Focal Cerebral Ischemia

Abstract

Background and Purpose-In contrast to early hypothermia, the effects of delayed hypothermia in focal cerebral ischemia have not been widely addressed. We examined the influence of delayed hypothermia on secondary ischemic injury, MRI lesion size, and neurological outcome after transient focal cerebral ischemia in a rat model. Methods-Rats (nϭ30) were subjected to transient middle cerebral artery occlusion (MCAO, 120 minutes) by use of the intraluminal filament model. Animals of the treatment group (nϭ12) were exposed to whole-body hypothermia of 33°C for 5 hours starting 3 hours after MCAO, whereas the control group (nϭ18) was kept at 37°C throughout the whole experiment. The normothermia-and hypothermia-treated animals were investigated daily by using the Menzies neurological score. Serial MRI was performed 1, 3, and 6 hours after MCAO and on days 1, 2, 3, and 5. After the final MRI scan, the rats were euthanized, and brain slices were stained by 2,3,5-triphenyltetrazolium chloride. Results-Delayed hypothermia resulted in a significant increase of survival rate and a significant improvement of the Menzies score. Moreover, a significant decrease in the extent of hyperintense volumes in T2-weighted scans and a reduction of cerebral edema as calculated from T2-weighted scans throughout the examination period were obvious. The extent of cerebral infarct volume and cerebral brain edema examined by MRI was consistent with 2,3,5-triphenyltetrazolium chloride staining. Conclusions-Our results suggest that even delayed postischemic hypothermia can reduce the extent of infarct volume and brain edema after transient focal cerebral ischemia.

Different Degrees of Hypothermia After Experimental Stroke

“…9 Cooling of the animals was performed immediately after middle cerebral artery occlusion (MCAO) of 90 minutes by using ice packs and temperature was maintained by adjusting the heating pad to the target temperature. 5 After the hypothermic period, rewarming was initiated by readjusting the temperature pad to 37°C. This goal was reached after 20 to 30 minutes subjected to the depth of the target temperature.…”

“…The areas of the nonischemic hemisphere, ischemic hemisphere, and infarction were multiplied by the slice thickness. The following formula was used to calculate the infarct volume corrected for the cerebral edema 5 : corrected infarct volumeϭvolume of the left, nonischemic hemisphereϪ(volume of the right, ischemic hemisphereϪinfarct volume). The volume of the brain edema has been calculated with the following formula: volume of the left, nonischemic hemisphereϪvolume of the right, ischemic hemisphere.…”

“…[1][2][3][4][5] Still, some issues concerning its appropriate use remain unsolved. The optimal depth is probably the most important factor.…”

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

“…Using this model it was found that transient (2 h) postischemic hypothermia to 321C failed to reduce infarct volume when initiated at the time of reperfusion after 1.5 h MCA occlusion, although further brain cooling to 301C could provide significant protection (Ren et al, 2004). This suggests a notably lower temperature threshold for postischemic hypothermic protection than has been observed in studies involving other strains, different occlusion methods, and/or longer cooling durations (Colbourne et al, 2000;Huh et al, 2000;Kollmar et al, 2002;Zhang et al, 1993a), including those that specifically targeted cooling during initial reperfusion (Ding et al, 2004), in which temperature reductions to 321C to 341C were typically effective. This study examined in detail the relationship between lesion size and regional temperature change at sites within and outside the MCA territory in a model of brief postischemic cooling in the SHR.…”

Nifedipine treatment reduces brain damage after transient focal ischemia, possibly through its antioxidative effects

“…[15][16][17] Briefly, after anesthesia was induced with pentobarbital (Dainabot, Tokyo, Japan), the rats were placed on a non-magnetic holder, which was placed into the bore of the MRI magnet. Spin-echo scout images were acquired first in the coronal and then in the sagittal planes to select reproducible coronal slice positions.…”