An Optimized Mouse Model for Transient Ischemic Attack

• Published in: Journal of neuropathology and experimental neurology Vol. 69; no. 2; pp. 188 - 195
• Main Authors: Pedrono, Eric, Durukan, Aysan, Strbian, Daniel, Marinkovic, Ivan, Shekhar, Shashank, Pitkonen, Miia, Abo-Ramadan, Usama, Tatlisumak, Turgut
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.02.2010; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Animals; Apoptosis; Biological and medical sciences; Brain - pathology; Brain - physiopathology; Cerebral Infarction - diagnosis; Cerebral Infarction - etiology; Disease Models, Animal; Follow-Up Studies; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery - complications; Ischemic Attack, Transient - complications; Ischemic Attack, Transient - diagnosis; Ischemic Attack, Transient - etiology; Ischemic Attack, Transient - physiopathology; Laser-Doppler Flowmetry; Magnetic Resonance Imaging; Male; Medical sciences; Mice; Mice, Inbred Strains; Necrosis; Nervous System Diseases - etiology; Neurology; Time Factors; Animal model; Stroke; Nervous system diseases; Transient ischemic attack; Rodentia; Middle cerebral artery; Cardiovascular disease; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Mouse; Animal; Imaging; Central nervous system disease; Cerebrovascular disease
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/NEN.0b013e3181cd331c

Transient ischemic attacks (TIAs) are brief neurological deficits ofcerebrovascular origin that are followed by complete clinical recovery. Although a plethora of animal models exist for ischemic stroke, a verified TIA model is lacking. We aimed to optimize such a model in mice, investigating the impact of varying durations (from 2.5 to 20 minutes) of intraluminal middle cerebral artery occlusion (MCAo). Three conditions were required to mimic clinical TIA reliably1) an objective demonstration of occlusion and reperfusion (assessed by laser Doppler flowmetry); 2) no permanent neurological deficit (assessed by sensorimotor neurological evaluation); and 3) no lesion at 24 hours after reperfusion (assessed by magnetic resonance imaging [MRI]). We observed high incidences of MRI lesions with MCAo durations of 15 minutes or longer. In contrast, no permanent neurological deficits or MRI lesions were observed in animals with MCAo below or equal to 10 minutes. Middle cerebral artery occlusion of 12.5 minutes rarely induced MRI lesions, but histopathologic evaluation using routine and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining revealed minute ischemic changes even after 2.5-minute MCAo. Abundance of necrotic and apoptotic changes gradually increased with the duration of ischemia. These results indicate that 10 minutes or shorter focal cerebral ischemia proves a suitable mouse TIA model; in addition, they indicate that MRI-negative microscopic ischemic damage may occur with even a few minutes of arterial occlusion.