Applications, modifications, and complications of an endovascular suture occlusion model of middle cerebral artery in different rat strains

Middle cerebral artery occlusion (MCAO) by endovascular suture placement has gained increasing acceptance because it is relatively noninvasive and allows for reperfusion. However, its application in rats has resulted in inconsistent infarction volumes that involve only the subcortex or subcortex plus some cortex. We proposed to characterize and study those factors that affect its reproducibility. Middle cerebral artery occlusion was induced by inserting an intraluminal 3-0 nylon suture into the circle of Willis through the external carotid artery in Sprague-Dawley (SD) and spontaneously hypertensive rats (SHR). Cerebral blood flow (CBF) was measured in all animals. The SD rats underwent 2 hours of occlusion followed by reperfusion. Animals were divided into four groups (10 in each group): single MCAO, single MCAO induced by a suture coated with poly-L-lysime (PLL, an adhesive compound), MCAO plus ipsilateral carotid occlusion (two-vessel occlusion [2VO]), MCAO plus bilateral carotid occlusion (three-vessel occlusion [3VO]). In the later group, 3 hours of MCAO was also performed. The SHRs were subjected to 1 and 2 hours of single occlusion of the MCA and then reperfusion (10 animals for each time point). Infarction volumes were measured using 2,3,5-tetrazolium chloride stain 3 days after the occlusion. In single MCAO, single MCAO-PLL, and 2VO groups in SD, the drop in CBF was not sufficient, resulting in inconsistent infarction. The CBF dropped to 27 ± 13% and 30 ± 18% of baseline in 3VO groups for the 2- and 3-hour groups, respectively. However, three rats (33%) in the 3VO group for 2 hours and one rat (10%) in 3VO group for 3 hours had only subcortical infarction. In SHRs, both 1-and 2-hour groups MCAO induced consistent infarction volume (288 ± 55 and 325 ± 73 mm1, respectively, p < 0.05). Overall this model resulted in subarachnoid hemorrhage (SAH) in 10% of both strains of rats. In these rats, a dramatic drop in CBF was noted immediately after reperfusion. No SAH occurred during insertion of the suture. Hemorrhagic infarction occurred overall in 24% of rats regardless of strain, and this was observed even in rats with small subcortical infarcts. Two animals died due to massive hemorrhagic infarction. Results of this study shows that endovascular suture occlusion of the MCA results in a consistent infarction in SHRs, whereas its application in SD rats, even with addition of both carotid artery occlusion, may give inconsistent infarction. To predict the outcome in terms of infarction volume, we suggest that in every animal measurement of CBF should be undertaken.