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...

SUMMARY We have evaluated the use of 2, 3, 5-triphenyltetrazolium chloride (TTC) as an histopathologic stain for identification of infarcted rat brain tissue. The middle cerebral artery (MCA) of 35 normal adult rats was occluded surgically. At various times after surgical occlusion, rats were sacrificed and brain slices were obtained and stained with TTC or hematoxolin and eosin (H & E); the size of the area of infarcted tissue stained by each method was quantified. In rats sacrificed 24 hr after occlusion of the MCA, the size of the area of infarction was 21 ± 2% of the coronal section for TTC, and 21 ± 2% for H & E (mean ± S.D., N = 13). The size of areas of infarction determined by either staining method was not significantly different in area by the paired t test, and a significant correlation between sizes determined by each method was found by linear regression analysis (r = 0.91, slope = 0.89, and the y intercept = 4.4%). Staining with TTC is a rapid, convenient, inexpensive, and reliable method for the detection and quantification of cerebral infarction in rats 24 hr after the onset of ischemia.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

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✓ Recent studies attempting to define the outcome from severe head injury have implied, directly or indirectly, that the severity of injury (as determined by the Glasgow Coma Scale (GSC)) is the sole determinant of outcome. Little attention has been focused on the type of lesion that causes the low GCS score, and there exists an unstated hypothesis that the lesion type is not an important determinant of outcome. No attempt has been made to determine whether patients who have the same GCS score caused by different lesions have the same or different outcomes. Since this is impossible to test without a large number of cases, data were obtained from seven head-injury centers on patients who fulfilled the Glasgow criteria for severe head injury (GCS ≤ 8 for at least 6 hours). Patients were categorized according to a simple classification system comprising seven lesion types, each of which was further subdivided into two GCS score ranges (3 to 5 and 6 to 8). Of 1107 patients, the overall mortality was 41%, but ranged from 9% to 74% among the different lesion categories. Conversely, 26% had good recovery (at 3 months), but among the different lesion groups the range was 6% to 68%. Acute subdural hematoma with GCS scores of 3 to 5 was uniformly the worst problem (74% mortality and 8% good recovery), whereas diffuse injury coma of 6 to 24 hours with GCS scores of 6 to 8 had 9% mortality and 68% incidence of good recovery. Results of this study demonstrate marked heterogeneity within this severe head-injury group and point out that patients with the same GCS score have markedly different outcomes, depending on the causative lesion. The type of lesion is thus as important a factor in determining outcome as is the GCS score, and both must be considered when describing severely head-injured patients.