Thromboembolic events lead to cortical spreading depression and expressionof c-fos, brain-derived neurotrophic factor, glial fibrillary acidic protein, and heat shock protein 70 mRNA in rats

The hypotheses that cerebral embolic events lead to repetitive episodes of cortical spreading depression (CSD) and that these propagating waves trigge r the expression of c-fos, brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and heat shock protein 70 (HSP70) mRNA we re tested. Wistar rats underwent photochemically induced right common carot id artery thrombosis (CCAT) (n = 18) or sham (n = 8) procedures. In a subgr oup of rats (n = 5), laser-Doppler flowmetry probes were placed overlying t he right parietal cortex to record CSD-Like changes in cortical blood flow during the initial 2-hour postinjury period. Rats were killed by decapitati on at 2 or 24 hours after CCAT, and brains were processed for in situ local ization of the gene expression. Two to five intermittent transient hyperemi c episodes lasting 1 to 2 minutes were recorded ipsilaterally after CCAT. A t 2 hours after CCAT, the widespread expression of c-fos and BDNF mRNAs was observed throughout the ipsilateral cerebral cortex. Pretreatment with the N-methyl-D-aspartate receptor blocker MK-801 (2 mg/kg) 1 hour before CCAT reduced the expression of BDNF mRNA expression at 2 hours. At 24 hours afte r CCAT, increased expression of GFAP mRNA was present in cortical and subco rtical regions. In contrast, multifocal regions of HSP70 expression scatter ed throughout the thrombosed hemisphere were apparent at both 2 and 24 hour s after injury. These data indicate that thromboembolic events lead to epis odes of CSD and time-dependent alterations in gene expression. The ability of embolic processes to induce widespread molecular responses in neurons an d glia may be important in the pathogenesis of transient ischemic attacks a nd may influence the susceptibility of the postembolic brain to subsequent insults including stroke.