A Critical Reevaluation of the Intraluminal Thread Model of Focal Cerebral Ischemia: Evidence of Inadvertent Premature Reperfusion and Subarachnoid Hemorrhage in Rats by Laser-Doppler Flowmetry

Abstract

Background and Purpose —The intraluminal thread model for middle cerebral artery occlusion (MCAO) has gained increasing acceptance. Numerous modifications have been reported in the literature, indicating that the technique has not been standardized. The present study was performed to evaluate and optimize the reliability of this model. Methods —One hundred Sprague-Dawley rats were subjected to MCAO by 2 different intraluminal filaments. Cortical blood flow was continuously monitored over both hemispheres by laser-Doppler flowmetry (LDF). In part I (3-0 filament), we evaluated the incidence of adequate MCAO, subarachnoid hemorrhage (SAH), intraluminal thrombus formation, and the effects of heparinization. In part II (silicone-coated 4-0 filament), we also determined the influence of insufficient MCAO on morphological and functional outcome and the incidence of postischemic hyperthermia. Results —In part I, SAH occurred in 30% and premature reperfusion in 24%. All animals with a decrease in contralateral flow had suffered SAH. Thrombus formation was not observed in any group. In part II, SAH occurred in 8% and premature reperfusion in 26%. There was no difference in outcome between rats with primary MCAO and rats with filament correction. Animals with uncorrected premature reperfusion had significantly smaller infarct volumes and fewer neurological deficits. Conclusions —SAH and insufficient MCAO may be more common in the intraluminal thread model than previously reported. Inadvertent premature reperfusion contributes to the interanimal variability associated with this model. The incidence of valid experiments increases with the use of a silicone-coated 4-0 filament. Continuous bilateral LDF is indispensable to monitor adequate MCAO and is highly sensitive to recognize SAH.