Gene expressions after thrombolytic treatment of middle cerebral artery clot embolism in mice

Background and Purpose-Thrombolytic treatment of stroke may result in reper fusion injury. To investigate the role of selective gene expressions, C57B1 /6J mice were subjected to middle cerebral artery (MCA) clot embolism, foll owed after I hour by intracarotid infusion of 10 mg/kg recombinant tissue p lasminogen activator (rtPA) or vehicle. Methods-Before the onset of treatment and at 1, 3, 6, and 24 hours of recir culation, animals were frozen in situ and hsp70, c-fos, junB. and NSE mRNAs were imaged on cryostat sections using in situ hybridization autoradiograp hy. Cerebral protein synthesis (CPS) and ATP content were measured on adjac ent brain sections. Results-hsp70 mRNA was upregulated in the penumbral cortex of untreated ani mals and in the MCA core region of animals receiving rtPA (ie, regions char acterized by a mismatch between high ATP levels and suppressed CPS). c-fos and junB mRNAs were transiently expressed mainly in the peri-infarct intact cortex for up to 3 to 6 hours in the treated and up to 24 hours in the unt reated animals. In both groups, NSE mRNA declined in the central parts of t he MCA territory together with a loss of silver impregnation, but this decl ine was more pronounced in the untreated animals. Conclusions-The genomic expression pattern after thrombolytic recanalizatio n of clot embolism resembles that of other types of transient ischemia such as reversible thread occlusion, although the outcome is markedly different . The investigated gene expressions, notably hsp70 mRNA, reflect the kind a nd severity of the ischemic stress, but they do not predict reversibility o f the ischemic injury.