Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.

Abstract

SUMMARY We have examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia. We developed a neurologic examination and have correlated changes in neurologic status with the size and location of areas of infarction.The MCA was surgically occluded at different sites in six groups of normal rats. After 24 hr, rats were evaluated for the extent of neurologic deficits and graded as having severe, moderate, or no deficit using a new examination developed for this model. After rats were sacrificed the incidence of infarction was determined at histologic examination. In a subset of rats, the size of the area of infarction was measured as a percent of the area of a standard coronal section.Focal (1-2 nun) occlusion of the MCA at its origin, at the olfactory tract, or lateral to the inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats, respectively (N = 38) and produced variable neurologic deficits. However, more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the olfactory tract -thus isolating lenticulostriate end-arteries from the proximal and distal supply -produced infarctions of uniform size, location, and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17). Neurologic deficit correlated significantly with the size of the infarcted area (Grade 2, N = 17, 28 ± 5% infarction; Grade 1, N = 5, 19 ± 5%; Grade 0, N = 3, 10 ± 2%; p < 0.05).We have characterized precise anatomical sites of the MCA that when surgically occluded reliably produce uniform cerebral infarction in rats, and have developed a neurologic grading system that can be used to evaluate the effects of cerebral ischemia rapidly and accurately. The model will be useful for experimental assessment of new therapies for irreversible cerebral ischemia. Stroke Vol 17, No 3, 1986 DEVELOPMENT of a reproducible, reliable animal model of cerebral ischemia would allow the study of the pathophysiology of the lesion and the efficacy of various treatment modalities. Characteristics of models are based on similarities with syndromes of human cerebrovascular disease; 1 a review of available models of focal ischemic infarction has been published recently.2 Ideally, experimental occlusion with or without reperfusion is accompanied by predictable changes in blood flow and a consistent degree of infarction that produces lesions of predictable location and size.2 " 4 To insure that the neurologic examination is reliable, animals should be neurologically similar to humans in terms of behavior, sensory-motor integration, and relative amount of neocortex.5 These requirements are best met by occlusion of a single artery in subhuman primates.2 -6 However, primates are costly and difficult to maintain and therefore cannot be used by the majority of investigators who study cerebral ischemia.The laboratory rat is a well-studied, relatively inexpensive, and readily available animal that h...

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