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(Stroke. 2006;37:2593.)
© 2006 American Heart Association, Inc.

Original Contributions

Long-Term Changes of Functional MRI–Based Brain Function, Behavioral Status, and Histopathology After Transient Focal Cerebral Ischemia in Rats

From the Center for Comparative Neuroimaging (K.M.S., C.F.F.), Department of Psychiatry, and the Department of Neurology (N.H., M.F.), University of Massachusetts Medical School, Worcester, Mass, and the Yerkes Imaging Center (T.Q.D.), Department of Neurology, Emory University, Atlanta, Ga.

Correspondence to Kenneth M. Sicard, Center for Comparative Neuroimaging (CCNI), University of Massachusetts Medical School, 303 Belmont St, Worcester, MA 01604. E-mail kenneth.sicard{at}umassmed.edu

Background and Purpose— The relation between recovery of brain function and neurological status after clinical and experimental cerebral ischemia is incompletely characterized. We assessed the evolution of ischemic injury, behavioral status, and brain activity at acute to chronic periods after transient middle cerebral artery occlusion (tMCAO) in rats.

Methods— Male Sprague-Dawley rats were subjected to 20-minute tMCAO (n=10) or sham operation (n=10). Sensorimotor behavioral testing and multimodal (diffusion, perfusion, T2, and functional) MRI, as well as postmortem hematoxylin-eosin staining, were performed before and up to 21 days after tMCAO. MRI and histological parameters were evaluated in 5 regions of interest within the sensorimotor network. Diffusion, perfusion, and T2 lesion volumes were calculated according to previously established viability thresholds.

Results— Diffusion and perfusion lesions were present during occlusion but disappeared completely and permanently within 30 minutes after reperfusion, with no T2 lesions seen. Functional MRI and behavioral deficits did not normalize until 1 and 21 days after tMCAO, respectively. Histology demonstrated selective neuronal cell death at 7 and 21 days after reperfusion.

Conclusions— Twenty-minute tMCAO produced distinct changes on multimodal MRI, histology, and behavioral parameters acutely and chronically. Normal findings on MRI after transient ischemia may not indicate normal tissue status, as behavioral and histological anomalies remain. Behavioral dysfunction persisting long after the recovery of MRI parameters may relate to the subtle neuronal damage seen on histology. Together, these results may help explain unremitting neurological deficits in stroke or transient ischemic attack patients with normal MRI findings.

Key Words: cerebral blood flow • magnetic resonance imaging, diffusion-weighted • magnetic resonance imaging, functional • magnetic resonance imaging, perfusion-weighted • middle cerebral artery occlusion

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