Experimental Model of Small Deep Infarcts Involving the Hypothalamus in Rats

Abstract

Background and Purpose —Intraluminal middle cerebral artery (MCA) occlusion in rats has been reported to cause hyperthermia assumed to be caused by hypothalamic damage. To clarify the effects of hypothalamic ischemia on body temperature and to obtain a model simulating lacunar infarction, we attempted to produce small infarcts in deep structures (including the hypothalamus). Methods —A surgical suture was advanced to occlude the origin of the hypothalamic (HTA) and/or anterior choroidal arteries (AChA) without compromise of the anterior or middle cerebral artery origins. After treatment, rectal temperature and postural reflex were examined repeatedly for 3 days under nonanesthetic conditions. The AChA and HTA and their link with small deep infarction were then confirmed by TTC, hematoxylin and eosin, and TUNEL stains and by microsurgical dissection after colored silicone perfusion into the cerebral arteries. Results —Advancement of the suture near to but not occluding the MCA origin (0.5 to 1.9 mm proximal) produced small, deep, nonneocortical stokes in 25 of 36 animals without producing MCA ischemic changes. These infarctions mainly affected the hypothalamus in 13 animals (HTA area: infarct volume 6±1 mm 3 ) and involved both the internal capsule and hypothalamus in 12 animals (HTA+AChA area infarct volume 48±10 mm 3 ). Rats with HTA infarction alone exhibited persistent hyperthermia for 72 hours; some also had transient mild postural abnormality. The AChA+HTA infarct group showed a transient elevation of body temperature for 24 hours and definitive postural abnormality. In the remaining 11 animals, the suture was inadvertently advanced across the MCA origin, producing a large infarct that affected both the neocortex (MCA territory) and nonneocortical structures (volume 381±30 mm 3 , n=11). The MCA infarct group displayed a transient hyperthermia and severe postural abnormality. Conclusions —When properly positioned, the intraluminal suture method permits selective AChA and/or HTA obstruction without inducing MCA territory ischemia. This model confirms that selective hypothalamic infarction produces significant and sustained temperature regulation abnormalities. The model also may be useful in investigating the pathophysiology of small, deep, end-vessel infarction.