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To investigate the changes of gene expression on the cerebral vasospasm after subarachnoid hemorrhage, we used genome-wide microarray for a canine double-hemorrhage model and analyzed the data by using a network-based analysis. Six dogs were assigned to two groups of three animals: control and hemorrhage. The effects were assessed by the changes in gene expressions in the artery 7 days after the first blood injection. Among 23,914 genes, 447 and 66 genes were up-regulated more than two- and fivefold, respectively, and 332 and 25 genes were down-regulated more than two- and fivefold, respectively. According to gene ontology, genes related to cell communication ( P = 5.28E-10), host–pathogen interaction (7.65E-8), and defense–immunity protein activity (0.000183) were significantly overrepresented. The top high-level function for the merged network derived from the network-based analysis was cell signaling, revealing that the subgroup that regulates the quantity of Ca2+ to have the strongest association significance ( P = 4.75E-16). Canine microarray analysis followed by gene ontology profiling and connectivity analysis identified several functional groups and individual genes responding to cerebral vasospasm. Ca2+ regulation may play a key role in these gene expression changes and may be involved in the pathogenesis of cerebral vasospasm. [ABSTRACT FROM AUTHOR]

A number of previous studies have revealed the abnormal expression of various angiogenesis-related genes or products in brain arteriovenous malformation (AVM). To understand the molecular process of this disease, we analyzed gene expression profiles in brain AVM. Using a DNA microarray consisting of 17,086 genes, we identified differentially expressed genes in 5 brain AVMs from their draining veins, vessels retaining basic venous architecture. Not many genes were differentially expressed between the AVM nidus and the draining vein. When we applied an absolute cut-off value for normalized log2 (cy5/cy3 ratio) of 0.4, 19 genes were selected. Genes such as SOX8, TRIM2, FENA1 (ephrin A1), and AQP4 were upregulated, and genes such as I_1000105, KRT18, IGFBP7, EMILIN-2, and KRT14 were downregulated. Genes relating to angiogenesis, such as vascular endothelial growth factor and angiopoietin and other members of the ephrin family, were not differentiated. Among differentially expressed genes detected in this analysis, we focused on ephrin A1, a gene related to embryogenesis and angiogenesis. The expression of ephrin A1 was two and three to nine times higher than that of the draining vein and normal brain, respectively, using real-time reverse transcription-polymerase chain reaction. For the first time, here we report the increased expression of ephrin A1 in brain AVM, which may play an important role in the pathogenesis of AVM. [ABSTRACT FROM AUTHOR]

A linkage region on chromosome 17cen has previously been found in 29 Japanese families with a history of familial intracranial aneurysms (IA). To investigate whether there is evidence of linkage in affected Japanese sib-pairs we performed nonparametric and parametric linkage analysis of a total of 253 familial aneurysm cases including 111 affected sib-pairs (ASP). Ten microsatellite markers covering a 17.7 cM region were chosen, in accordance with previous work in which nominal P had been below 0.05. Statistical analysis was performed by use of Genehunter and Sibpal software. After calculation of the logarithm of the odds (LOD) and nonparametric linkage analysis (NPL) scores our study did not show any linkage in the region analyzed. Our conclusion did not change even after only ASP were analyzed. In contrast with a previous study examining multigenerational Japanese families with IA, most Japanese ASP may not have a genetic linkage to chromosome 17 cen. [ABSTRACT FROM AUTHOR]

We previously performed a genome-wide linkage study of intracranial aneurysm (IA) and found positive evidence of linkage at chromosomes 5q22-31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, fibroblast growth factor 1 (FGF1), fibrillin 2 (FBN2), and lysyl oxidase gene (LOX) lie, and evaluate associations with IA. Genomic DNAs were obtained from 172 IA patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in FGF1, FBN2, and LOX, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in FGF1 (χ[SUB2] = 4.44, df=1, P=0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (χ[SUB2] =16.04, df=1, P=0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in FGF1 according to the linkage disequilibrium structure. No associations of FBN2 and LOX with IA were detected in the present study. [ABSTRACT FROM AUTHOR]