Differences in ischemic lesion evolution in different rat strains using diffusion and perfusion imaging.
OBJECTIVE
Interstrain differences in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. We investigated, in 2 commonly used rat strains (Sprague-Dawley [SD] and Wistar-Kyoto [WK]), the spatiotemporal evolution of ischemia after permanent suture MCAO using diffusion and perfusion imaging.


METHODS
Serial measurements of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were performed up to 210 min after MCAO. Lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO.


RESULTS
While the ADC-derived lesion volume increased rapidly during the first 120 min after MCAO and essentially stopped growing after 3 hours in SD rats, ADC lesion in WK rats increased progressively during the entire 210-min period and was significantly smaller at all time points (P<0.05). The abnormal perfusion volume correlated highly with the TTC-defined infarct size in both groups. In WK rats, the abnormal perfusion volume was significantly larger than the abnormal diffusion volume up to 90 min after MCAO (P<0.001), whereas the diffusion/perfusion mismatch was significant (P<0.001) only at 45 min in SD rats. ADC-CBF scatterplots analysis revealed a slower and less robust ADC decline over time in WK rats in pixels with severe (<20% of normal) and moderate (21 to 40% of normal) CBF reduction.


CONCLUSIONS
This study demonstrated substantial differences in acute ischemic lesion evolution between SD and WK rats. These interstrain variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.
Bardutzky
Juergen
J
Department of Neurology, University of Heidelberg, Heidelberg, Germany. juergen_bardutzky@med.uni-heidelberg.de
Shen
Qiang
Q
Henninger
Nils
N
Bouley
James
J
Duong
Timothy Q
TQ
Fisher
Marc
M
D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D004396:Coloring Agents / Q000494:pharmacology; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007511:Ischemia / Q000473:pathology; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013778:Tetrazolium Salts / Q000494:pharmacology; D013997:Time Factors
D004396:Coloring Agents; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium