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

Background and Purpose - Thrombolytic treatment of stroke may result in reperfusion injury. To investigate the role of selective gene expressions, C57B1/6J mice were subjected to middle cerebral artery (MCA) clot embolism, followed after 1 hour by intracarotid infusion of 10 mg/kg recombinant tissue plasminogen activator (rtPA) or vehicle. Methods - Before the onset of treatment and at 1, 3, 6, and 24 hours of recirculation, animals were frozen in situ and hsp70, c-fos, junB, and NSE mRNAs were imaged on cryostat sections using in situ hybridization autoradiography. Cerebral protein synthesis (CPS) and ATP content were measured on adjacent brain sections. Results - hsp70 mRNA was upregulated in the penumbral cortex of untreated animals and in the MCA core region of animals receiving rtPA (ie, regions characterized 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 untreated animals. In both groups, NSE mRNA declined in the central parts of the MCA territory together with a loss of silver impregnation, but this decline was more pronounced in the untreated animals. Conclusions - The genomic expression pattern after thrombolytic recanalization 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 and severity of the ischemic stress, but they do not predict reversibility of the ischemic injury.