Long-term changes of functional MRI-based brain function, behavioral status, and histopathology after transient focal cerebral ischemia in rats
Department of Neurology; Graduate School of Biomedical Sciences
Animals; *Behavior, Animal; Brain; Brain Damage, Chronic; Cell Death; Diffusion Magnetic Resonance Imaging; Hypercapnia; Infarction, Middle Cerebral; Artery; Ischemic Attack,; Transient; *Magnetic Resonance Imaging; Male; Movement Disorders; Neurons; Perceptual Disorders; Rats; Rats, Sprague-Dawley; Reaction Time; Sensation Disorders
Nervous System Diseases | Neurology
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.
DOI of Published Version
Stroke. 2006 Oct;37(10):2593-600. Epub 2006 Aug 31. Link to article on publisher's site
Stroke; a journal of cerebral circulation
Sicard, Kenneth M.; Henninger, Nils; Fisher, Marc; Duong, Timothy Q.; and Ferris, Craig F., "Long-term changes of functional MRI-based brain function, behavioral status, and histopathology after transient focal cerebral ischemia in rats" (2006). Neurology Publications and Presentations. 64.