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 6Ϯ1 mm 3 ) and involved both the internal capsule and hypothalamus in 12 animals (HTAϩAChA area infarct volume 48Ϯ10 mm 3 ). Rats with HTA infarction alone exhibited persistent hyperthermia for 72 hours; some also had transient mild postural abnormality. The AChAϩHTA 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 381Ϯ30 mm 3 , nϭ11). 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. (Stroke. 1999;30:2743-2751.)

Lasting Pure-Motor Deficits after Focal Posterior Internal Capsule White-Matter Infarcts in Rats

“…22 Although selective occlusion of the anterior choroidal artery in pigs has created small infarcts mainly involving the internal capsule, 23 in rodents infarcts have also involved thalamus and hypothalamus, thereby limiting the usefulness of this approach. 24 Global hypoperfusion (e.g., bilateral carotid occlusion in rats 25 or stenosis in mice 26 ) does lead to diffuse blood flow reduction, white-matter rarefaction, and cumulative ischemic damage, but lesions mimic more chronic progressive leukoaraiosis rather than sudden-onset focal ischemic whitematter infarction. Photothrombosis has recently been used to target the internal capsule causing motor deficits lasting at least 3 weeks.…”

Neuroprotective Effects of MK-801 in Different Rat Stroke Models for Permanent Middle Cerebral Artery Occlusion

“…1 The most important drawback of this technique, however, is the pathological increase of body temperature (Ͼ39°C) when this model is used for permanent MCAO. [2][3][4][5][6] It is widely accepted from experimental and clinical studies that hyperthermia increases infarct volume and worsens functional outcome. 4,[7][8][9][10] Hyperthermia can influence the evaluation of neuroprotective compounds in experiments in which the suture occlusion model is used.…”

Models That Matter: White Matter Stroke Models

“…The infarct size and location is more variable in this model than with the ET-1 method [38]. Accordingly, the postural reflex test showed varied grades but a consistent deficit in the postural reflex test that persisted for 72 h [37].…”

“…The anterior choroidal artery (AchA) is a branch of the internal carotid artery that arises just proximal to the carotid bifurcation into middle and anterior cerebral arteries [37]. Intraluminal occlusion of the AchA in the rat creates an ischemic core that involves the internal capsule, although the infarct size may vary and the hypothalamus may also be involved [37,38].…”

“…Intraluminal occlusion of the AchA in the rat creates an ischemic core that involves the internal capsule, although the infarct size may vary and the hypothalamus may also be involved [37,38]. 2,3,5-triphenyltetrazolium chloride (TTC) staining and cell death assays show a successful modeling of capsular lacunar infarct with this method.…”