Spontaneous Hyperthermia and its Mechanism in the Intraluminal Suture Middle Cerebral Artery Occlusion Model of Rats

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Abstract
Background and Purpose —The intraluminal suture middle cerebral artery occlusion (MCAO) model is increasingly used in experimental stroke studies. The purposes of this study were to determine whether (1) spontaneous hyperthermia occurs after different periods of MCAO in this model, (2) hypothalamic injury contributes to hyperthermia, and (3) hyperthermia increases infarct volume after permanent MCAO. Methods —Rats were subjected to 60, 90, and 120 minutes of transient MCAO (n=8 per group), permanent MCAO (n=8 per group, 5 groups), and permanent hypothalamic occlusion, in which an occluder was inserted 15 to 15.5 mm to block only the hypothalamic branch from the internal carotid artery (n=4) with the use of the intraluminal suture MCAO method. In one group undergoing permanent MCAO, the body temperature was maintained at 37°C throughout the experiment. In another group (n=4) undergoing 90 minutes of temporary MCAO, diffusion- and perfusion-weighted imaging were performed to document the in vivo ischemic changes in the hypothalamus. Body temperature was measured hourly for 12 hours. At 24 hours (12 hours in 2 permanent MCAO groups), triphenyltetrazolium chloride staining was used to verify ischemic hypothalamic injury and to calculate corrected infarct volumes. Results —Spontaneous hyperthermia (>39°C) occurred in the 120-minute group, all permanent MCAO groups, and the hypothalamic occlusion group but not in the 60-minute or the 90-minute groups. Hypothalamic infarction was found in 1 rat each in the 60-minute and 90-minute groups, 6 of the 8 rats in the 120-minute group, 37 of the 40 rats in the permanent occlusion groups, and all 4 rats in the hypothalamic occlusion group. After 90 minutes of transient MCAO, the decreased cerebral blood flow and apparent diffusion coefficient values in the hypothalamic region during occlusion recovered fully 2 hours after reperfusion. The corrected infarct volumes were identical in all permanent occlusion groups. Conclusions —The intraluminal suture MCAO lasting for ≥2 hours induces spontaneous hyperthermia that is associated with hypothalamic injury, and delayed spontaneous hyperthermia does not increase infarct volume after permanent intraluminal suture MCAO.