Transient MRI-detected water apparent diffusion coefficient reduction correlates with c-fos mRNA but not hsp70 mRNA induction during focal cerebral ischemia in rats

Cerebral ischemia induces immediate early genes such as c-Sos and stress ge nes such as hsp70, In this study, the spatial relationships between c-fos a nd hsp70 mRNA expression and changes detectable with diffusion and perfusio n magnetic resonance (MR) imaging were examined. The middle cerebral artery (MCA) of young adult rats was occluded for 30 or 60 min, Diffusion MR (D-M R) images were acquired continuously during the ischemic period and dyspros ium-contrast perfusion (P-MR) images were acquired at the end of the ischem ic period. C-fos and hsp70 mRNA expression were examined with in situ hybri dization. The most significant finding of this work was that for both durat ions of ischemia, c-fos induction was observed in cortical and sub-cortical regions exhibiting a transient reduction in the apparent diffusion coeffic ient of water (ADC). Transients which occurred on a time scale of 3 min may have been caused by spreading depression. Those occurring on a 10-min time scale may have been caused by an initial reduction in blood flow with occl usion that was followed by an ischemia-induced increase in collateral blood flow. P-MR imaging showed that perfusion in c-fos positive regions was hig her than in regions with persistently reduced ADC. Hsp70 induction did not correlate with transient ADC reduction. It was induced in the MCA territory in regions showing persistent ADC changes, with induction being greatest a t the periphery of these regions. It was also induced in regions that exhib ited both spontaneous reversal of the diffusion changes and decreased perfu sion. (C) 1999 Elsevier Science B.V. All rights reserved.