Thromboembolic events lead to cortical spreading depression and expression of 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 trigger the expression of c-fos, brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and heat shock protein 70 (HSP70) mRNA were tested. Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) (n = 18) or sham (n = 8) procedures. In a subgroup of rats (n = 5), laser-Doppler flowmetry probes were placed overlying the right parietal cortex to record CSD-like changes in cortical blood flow during the initial 2-hour postinjury period. Rats were killed by decapitation at 2 or 24 hours after CCAT, and brains were processed for in situ localization of the gene expression. Two to five intermittent transient hyperemic episodes lasting 1 to 2 minutes were recorded ipsilaterally after CCAT. At 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 after CCAT, increased expression of GFAP mRNA was present in cortical and subcortical regions. In contrast, multifocal regions of HSP70 expression scattered throughout the thrombosed hemisphere were apparent at both 2 and 24 hours after injury. These data indicate that thromboembolic events lead to episodes of CSD and time-dependent alterations in gene expression. The ability of embolic processes to induce widespread molecular responses in neurons and glia may be important in the pathogenesis of transient ischemic attacks and may influence the susceptibility of the postembolic brain to subsequent insults including stroke.
Dietrich
W D
WD
Department of Neurology, Cerebral Vascular Disease Research Center, University of Miami School of Medicine, Florida 33101, USA.
Truettner
J
J
Prado
R
R
Stagliano
N E
NE
Zhao
W
W
Busto
R
R
Ginsberg
M D
MD
Watson
B D
BD
D000818:Animals; D001345:Autoradiography; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006439:Hemodynamics; D017403:In Situ Hybridization; D020766:Intracranial Embolism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D018840:HSP70 Heat-Shock Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger