A new middle cerebral artery occlusion model for intra-arterial drug infusion in rats

With the wide application of intra-arterial therapy for cerebrovascular disorders, preclinical intra-arterial drug-delivery studies based on middle cerebral artery occlusion (MCAO) models have become urgent. In the present study, a novel stroke model was developed for intra-arterial drug delivery: MCAO and drug delivery were accomplished using a microcatheter device. MCAO was induced in Sprague-Dawley rats using the microcatheter device (cMCAO group, n=10) or a nylon suture (sMCAO group, n=10). After 24-h occlusion, neurological deficit and infarct volume were compared between the groups. Drug-delivery models used in stroke studies were compared with the present model to verify the drug-delivery ability of the microcatheter device. MCAO was induced using the microcatheter device in 21 Sprague-Dawley rats. At 4h after occlusion, 2% Evans blue dye was infused using different methods, and 1h later, the dye was extracted from each hemisphere and spectrophotometrically quantified. All cMCAO group rats showed neurological deficits; none developed subarachnoid hemorrhage or died before sacrifice. Neurological deficits and infarct volumes were similar in the cMCAO and sMCAO groups. Significantly more dye leakage occurred in the ischemic hemispheres of the rats that received the dye via the microcatheter device. Compared to other intra-arterial drug-delivery models used in stroke studies, the present model was easily established, had a high success rate, caused minimal surgical injury, and enabled highly efficient drug delivery. Thus, the present model is an efficient tool for investigating the effect of intra-arterial drug delivery on ischemic cerebral tissue.