MRI analysis of the changes in apparent water diffusion coefficient, T(2) relaxation time, and cerebral blood flow and volume in the temporal evolution of cerebral infarction following permanent middle cerebral artery occlusion in rats.
Detailed knowledge of similarities and differences between animal models and human stroke is decisive for selecting clinically effective drugs based on efficacy data obtained preclinically. Differences in the temporal evolution of stroke pathologies between animal models and man have been reported. In view of the importance of this issue for the development of neuroprotective treatments, the temporal evolution of stroke pathologies in the rat permanent middle cerebral artery occlusion (pMCAO) model has been evaluated with magnetic resonance imaging modalities under experimental conditions matching as close as possible those used in humans. Changes in the ipsilateral and contralateral cortex and striatum of cerebral blood flow (CBF) and volume (CBV), apparent diffusion coefficient (ADC), and spin-spin relaxation time (T(2)), as well as total cortical and striatal infarct volumes, calculated from CBF, ADC, and T(2) maps, were determined starting 1 h up to 216 h post-pMCAO. The temporal evolution of the MRI parameters in this rat model was similar to that observed in humans. In particular, the ADC values were decreased for more than 3 days and returned back to baseline between 4 to 8 days, to increase by day 9 only. Thus the stroke pathology in this rat model develops at a similar pace as in stroke patients arguing against a fundamental difference in the mechanisms involved. The infarct volumes however develop differently in this rat model as they invariably increase over the first 48 h, while in humans the evolution of infarct volume is slower and more heterogeneous.
Rudin
M
M
Core Technology, Novartis Pharma AG, Basel, CH-4002, Switzerland.
Baumann
D
D
Ekatodramis
D
D
Stirnimann
R
R
McAllister
K H
KH
Sauter
A
A
D000818:Animals; D001783:Blood Flow Velocity; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002544:Cerebral Infarction / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology; D004058:Diffusion; D004195:Disease Models, Animal; D018450:Disease Progression; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D014867:Water / Q000378:metabolism*
D014867:Water