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-fos and stress genes such as hsp70. In this study, the spatial relationships between c-fos and hsp70 mRNA expression and changes detectable with diffusion and perfusion 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-MR) images were acquired continuously during the ischemic period and dysprosium-contrast perfusion (P-MR) images were acquired at the end of the ischemic period. C-fos and hsp70 mRNA expression were examined with in situ hybridization. The most significant finding of this work was that for both durations of ischemia, c-fos induction was observed in cortical and sub-cortical regions exhibiting a transient reduction in the apparent diffusion coefficient 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 occlusion that was followed by an ischemia-induced increase in collateral blood flow. P-MR imaging showed that perfusion in c-fos positive regions was higher 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 at the periphery of these regions. It was also induced in regions that exhibited both spontaneous reversal of the diffusion changes and decreased perfusion.
Mancuso
A
A
Department of Neurological Surgery, University of California at San Francisco and the Department of Veterans Affairs Medical Center, 4150 Clement St., San Francisco, CA 94121, USA. tony@mail.mmrrcc.upenn.edu
Derugin
N
N
Ono
Y
Y
Hara
K
K
Sharp
F R
FR
Weinstein
P R
PR
D000818:Animals; D001834:Body Water / Q000378:metabolism*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D004058:Diffusion; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D002546:Ischemic Attack, Transient / Q000175:diagnosis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010477:Perfusion; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger