A model of global forebrain ischemia/reperfusion in the awake rat

Anesthesia is an essential element during the induction of ischemia/reperfusion and cerebral blood flow (CBF) measurement in most animal models. Cerebral neuroprotection and intrinsic effects on CBF afforded by anesthetics are confounding variables in those models. A new model of global forebrain ischemia/reperfusion (GFIR) in awake rats is presented and characterized. Rats underwent permanent occlusion of the basilar, and the paired pterygopalatine, external carotid, and occipital arteries. Inflatable balloon occluders were inserted around both common carotids, the nine-vessel occlusion (9VO) preparation. A subgroup of 9VO rats underwent placement of a laser Doppler flowmetry (LDF) probe for measurement of cortical CBF. Twenty-four hours later, while awake, 9VO rats were subjected to 10 min of ischemia by occluding both common carotid arteries. Blood gases, glucose and hematocrit were analyzed before and during ischemia, and for up to 90 min during reperfusion. Behavioral observations and continuous LDF CBF and mean arterial blood pressure determinations during ischemia and reperfusion were made. Rats were rendered comatose and decerebrate rigidity was observed during 9VO. Following balloon deflation, rats immediately regained the righting reflex and achieved complete recovery in the next 24 h. Moderate hyperglycemia was observed at 5 min of ischemia and up to 90 min reperfusion in 9VO rats. LDF CBF decreased to 5% of baseline and remained unchanged during ischemia. The 9VO is a reproducible recovery model of GFIR. Behavioral and LDF CBF correlates are consistent and survival studies are feasible.