Gene expression profiles in the peri-infarct brain cortex in a rat model of stroke-prone renovascular hypertension

BACKGROUND:Previous studies have focused on gene expression acutely following stroke onset. However,there have been a few reports of gene expression during later stages of cerebral infarction. OBJECTIVE:To determine gene expression profiling in the peri-infarct brain cortex 7 days after ischemia in a rat model of cerebral infarction in renovascular hypertensive rats. DESIGN,TIME AND SETTING:An in vivo,molecular experiment was performed at the Experimental Animal Center of Sun Yat-sen University and CapitalBio,Beijing,China between February 2004 and August 2005. MATERIALS:A 70-mer oligo chip containing 5 705 rat genes was supplied by CapitalBio,Beijing, China;and the Oligo rat gene bank was provided by Qiagen,the Netherlands. METHODS:Six Sprague Dawley rats were utilized to establish a stroke-prone renovascular hypertensive model using the two-kidney and two-clip method.The rats were subsequently randomly assigned to two groups:middle cerebral artery occlusion and sham-operation,with three rats in each group.The middle cerebral artery occlusion model was induced by intraluminal suture method.Incisions were sutured following isolation of carotid arteries in the sham-operation group. MAIN OUTCOME MEASURES:Total RNA was extracted from the peri-infarct cerebral cortex 7 days after surgery.Following fluorescent labeling,RNA was hybridized to an Oligo chip containing 5 705 genes and was then scanned.Images were collected and the differentially expressed genes (number and category) were selected by data analysis. RESULTS:A total of 174 genes were upregulated,and 23 were down regulated,in the peri-infarct cerebral cortex 7 days after ischemia.The upregulated genes were distributed among 12 functional categories,and the downregulated genes belonged to categories of transport,transcription regulators,signals,response to stress,metabolism,and cell adhesion.The expression of some cytoskeletal genes was upregulated,including VIM,A2M,B2M,ACTR3,and ARPC1B.Expression of a few cell adhesion-related genes(such as NLGN1,LGALS1,LGALS3,COL1A1,COL2A1,and SPP1) and other inflammation-related genes(such as C1QB,C1S,C4,C5R1,CFH,CD14,CD164, CD47,CD48,CD53,CD8B,IFNGR,and TFITM2) were upregulated.The glutamate-receptor gene GRIK5 was downregulated,which is related to the excitatory neurotransmitter glutamate.However, expression of the inhibitory neurotransmitter GABA-related genes was bidirectional - namely, GABRA5 downregulation and GABARAP upregulation. CONCLUSION:Upregulation of many cell adhesion and inflammation related genes and downregulation of excitatory glutamate-related receptor genes revealed active gene expression during later stages of cerebral infarction,which suggested molecular mechanisms of injury or repair.

The Possibility and Molecular Mechanisms of Cell Pyroptosis After Cerebral Ischemia

Introduction Stroke is an important disease that is prevalent worldwide [1-3].Ischemic stroke accounts for 80%of stroke cases. Currently,evidence-based effective treatments for ischemic stroke are limited,and only intravenous throm- bolysis with Alteplase (a commercially available throm- bolytic agent)within 4.5 h of stroke onset and thrombectomy and arterial thrombolysis within 6-24h of onset are effective [4,5].However,because these two treatments have strict indications and certain risks (reper- fusion injury and bleeding)[5-8],there is an urgent need to develop new treatment methods.Thus,comprehensive elucidation of the molecular mechanisms underlying ischemic brain damage and the search for key signaling pathways and protein molecules are important for guiding the clinical treatment of ischemic stroke.

An MA-MRR model for transaction-level analysis of highfrequency trading processes

The transaction-level analysis of security price changes by Madhavan,Richardson,and Roomans(1997,hereafter MRR)is a useful framework for financial analysis.The first-order Markov property of trading indicator variables is a critical assumption in the MRR model,which contradicts the information lag empirically demonstrated in high-frequency trading processes.In this study,a nonparametric test is employed,which shows that the Markov property of the trading indicator variables is rejected on most trading days.Based on the spread decomposed structure,an MA-MRR model was proposed with a moving average structure adopted to absorb the information lag as an extension.The empirical results show that the information lag plays an important role in measuring the adverse selection risk parameter and that the difference in this parameter between the original and the extension is significant.Furthermore,our analysis suggests that the information lag parameter is a useful measure of the average speed at which information is incorporated into prices.