The macrosphere model: Evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats

Abstract

Background and purpose: The suture middle cerebral artery occlusion (MCAO) model is widely used for the simulation of focal cerebral ischemia in rats. This technique causes hypothalamic injury resulting in hyperthermia, which can worsen outcome and obscure neuroprotective effects. Herein, we introduce a new MCAO model that avoids these disadvantages. Methods: Permanent MCAO was performed by intraarterial embolization using six TiO 2 macrospheres (0.3–0.4 mm in diameter) or by the suture occlusion technique. Body temperature was monitored, functional and histologic outcome was assessed after 24 h. Additional 16 rats were subjected to macrosphere or suture MCAO. Lesion progression was evaluated using magnetic resonance imaging (MRI). Results: The animals subjected to suture MCAO developed hyperthermia (>39 °C), while the temperature remained normal in the macrosphere MCAO group. Infarct size, functional outcome and model failure rate were not significantly different between the groups. Lesion size on MRI increased within the first 90 min and remained unchanged thereafter in both groups. Conclusions: The macrosphere MCAO model provides reproducible focal cerebral ischemia, similar to the established suture technique, but avoids hypothalamic damage and hyperthermia. This model, therefore, may be more appropriate for the preclinical evaluation of neuroprotective therapies and can also be used for stroke studies under difficult conditions, e.g., in awake animals or inside the MRI scanner.