Characterization of a novel thrombotic middle cerebral artery occlusion model in monkeys that exhibits progressive hypoperfusion and robust cortical infarction.
In an attempt to establish a thrombotic middle cerebral artery (MCA) occlusion model using cynomolgus monkeys, we measured the blood flow in the main MCA tract and cerebral cortex, brain damage, and neurological deficits, and compared them with those of mechanical MCA occlusion model. Thrombotic occlusion was induced photochemically by green light application on the MCA following rose bengal treatment; mechanical occlusion was induced by MCA clipping for 3h. Patency of the main MCA tract showed two patterns in the thrombotic model: permanent occlusion or cyclical flow reduction (CFR). Regional cerebral blood flow (rCBF) decreased during occlusion followed by post-ischemic hyperperfusion in the clipping model, whereas rCBF reduction expanded time-dependently in the thrombotic occlusion model. Brain infarction and neurological scores in the thrombotic occlusion model were significantly larger than those in the clipping occlusion model. In histological assessment, microthrombi containing myeloperoxidase- and fibrinogen-positive cells were observed in the cortex following the thrombotic but not clipping occlusion. These results collectively suggest that this thrombotic MCA occlusion model, because it shows impairment of cerebral microcirculation, could provide a vital platform for understanding progressive ischemia as well as for evaluating potential therapeutic drugs.
Maeda
Masashi
M
Department of Neuroscience, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 2-1-6 Kashima, Yodogawa-Ku, Osaka 532-8514, Japan. masashi_maeda@po.fujisawa.co.jp
Takamatsu
Hiroyuki
H
Furuichi
Yasuhisa
Y
Noda
Akihiko
A
Awaga
Yuji
Y
Tatsumi
Mitsuyoshi
M
Yamamoto
Masashi
M
Ichise
Rikiya
R
Nishimura
Shintaro
S
Matsuoka
Nobuya
N
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology; D002544:Cerebral Infarction / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005340:Fibrinogen / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging* / Q000503:physiopathology; D020767:Intracranial Thrombosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008252:Macaca fascicularis; D008297:Male; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009195:Peroxidase / Q000378:metabolism; D010775:Photic Stimulation / Q000379:methods; D049268:Positron-Emission Tomography; D012395:Rose Bengal / Q000528:radiation effects; D013525:Surgical Instruments
D015415:Biomarkers; D012395:Rose Bengal; D005340:Fibrinogen; D009195:Peroxidase