SUMMARY A method for the volumetric assessment of early cerebral infarction, together with its statistical and biological validation, is described. In halothane anaesthetised rats the stem of the right middle cerebral artery was occluded and 3 hours later (with full monitoring of respiratory and cardiovascular status) the animals were killed by perfusion fixation. In normotensive normocapnic animals the volume of infarction was 52 + 4mm3 in the cerebral cortex and 21 + 1 mm3 in the corpus striatum. The reproducibility of the volumetric assessment was found to be excellent (coefficient of correlation 0995 on 18 replicate measurements). The minimum number of stereotactic levels which must be assessed to yield accurate volumetric measurements of infarction is 8. The method is sensitive at detecting alterations in the amount of infarction. For example, it can readily detect the increase in amount of structural damage in cerebral cortex following a transient episode of hypotension. This approach allows an objective assessment of drug therapy and management strategies in the treatment of cerebral infarction.Numerous attempts have been made to produce experimentally an ischaemic lesion resembling that seen in man. One of the most commonly used methods has been to occlude the middle cerebral artery in various experimental animals`6 in the belief that proximal occlusion of this artery is equivalent to a large focal cerebral infarct in man.We have developed a technique for occluding the middle cerebral artery (MCA) in the rat7 which has proved useful for correlating local cerebral blood flow8 and dysfunction of the blood-brain barrier9 with histological evidence of ischaemic brain damage. 10 In this paper we detail a rigorous means for measuring the volume of early cerebral infarction in the rat after occlusion of the middle cerebral artery. This method, with its statistical validation, together with a demonstration of its ability to measure changes in the amount of structural damage in various experimental conditions, is described. Some of this data has appeared previously in abstract form." Materials and methods General preparationThirteen adult male Sprague Dawley rats (weighing between 320-415 g each) were anaesthetised and ventilated mechanically with a nitrous oxide/oxygen mixture (70%:30%) and, during the surgical procedures, 2% halothane. Polyethylene catheters were inserted into both femoral arteries and veins to allow the continuous monitoring of blood pressure, repeated sampling of arterial blood and the administration of drugs. The body temperature was monitored by a rectal thermometer and the animals were maintained at normothermia by external heating.In normotensive animals, if there was a transient reduction in mean arterial blood pressure below 80mm Hg for more than two minutes during the observation period of 3-4 hours after occlusion of the MCA, the animals were not processed for inclusion in the study.Operative procedure The proximal portion of the MCA was occluded permanently under halothane anaesthesi...