Reduced Severity of Outcome of Recurrent Ipsilateral Transient Cerebral Ischemia Compared with Contralateral Transient Cerebral Ischemia in Rats.

BACKGROUND:To investigate whether prior transient ischemic attack (TIA) had a preconditioning effect on subsequent cerebral infarction in a rat model using middle cerebral artery occlusion (MCAO). METHODS:Thirty-six adult male Sprague-Dawley rats were divided into 3 groups: those with transient (5 minutes) left MCAO (left TIA) (n = 15), those with transient right MCAO (right TIA) (n = 15), and a sham operation group (n = 6). Seven days after the initial transient MCAO, rats in all groups underwent permanent left MCAO. After 24 hours, all rats underwent motor function measurement (the Garcia score and tilting plane test), magnetic resonance imaging, postmortem brain examination, and biomarkers of stroke. RESULTS:Following permanent MCAO, the Garcia score, the brain edema area of T2-weighted images, brain infarction volume, and the level of tumor necrosis factor α mRNA of the ipsilateral and contralateral TIA groups showed no significant difference. The angle of sliding off in the tilting plane test, the mean intensity of the brain edema area of T2-weighted images, levels of matrix metalloproteinase 9, interleukin-1β, inducible nitric oxide synthase mRNA, and apoptosis-related proteins, BAX, and phosphorylated-p38, were lower in the ipsilateral TIA group compared with the contralateral TIA group. CONCLUSION:The main finding of this study was that a transient, mild, unilateral focus of cerebral ischemia (or TIA) in either the left or right hemisphere, which is then followed by a second unilateral severe and focal ischemic event, results in brain injury. The severity of the brain injury following this second ischemic event will be alleviated when the second insult is ipsilateral to the first TIA.