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.
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada. nikolova@imaging.robarts.ca
Simona
S
Nikolova
Slavianka
S
Moyanova
Sarah
S
Hughes
Miranda
M
Bellyou-Camilleri
Ting-Yim
TY
Lee
Robert
R
Bartha
D000704:Analysis of Variance; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage*; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008845:Microinjections; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D014057:Tomography, X-Ray Computed
D019332:Endothelin-1