Endothelin-1 induced MCAO: dose dependency of cerebral blood flow

The purpose of this study was to characterize the magnitude and duration of cerebral blood flow (CBF) reduction in the somatosensory cortical region in a rat model of middle cerebral artery occlusion (MCAO) induced by endothelin-1 (ET1) microinjection under isoflurane anesthesia. MCAO was induced by microinjection of ET1 proximal to the MCA in 41 isoflurane-anesthetized male Sprague-Dawley rats. Three doses of ET1 were studied, 60 pmol (Group 1), 150 pmol (Group 2), and 300 pmol (Group 3). CBF was monitored for 4h following injection using a laser Doppler probe stereotaxically inserted into the left somatosensory cortical region. Computed tomography perfusion imaging was used to verify the extent and duration of blood flow reduction in a subset of 12 animals. The magnitude and duration of blood flow reduction was variable (60-92% of baseline). The 300 pmol dose provided the greatest sustained decrease in blood flow. Evidence of tissue damage was obtained in cases where CBF decreased to <40% of baseline. At the doses studied, ET1-induced ischemia in the presence of isoflurane anesthesia can be used as a minimally invasive but variable model of MCAO. The model is well suited for acute imaging studies of ischemia.