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Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.

Bailey EL, McBride MW, Beattie W, McClure JD, Graham D, Dominiczak AF, Sudlow CL, Smith C, Wardlaw JM - Neuropathol. Appl. Neurobiol. (2014)

Bottom Line: We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats.All were present at age 5 weeks thus predating blood pressure elevation. 'Neurological' and 'inflammatory' pathways were more affected than 'vascular' functional pathways.Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD.

View Article: PubMed Central - PubMed

Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.

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Heat maps were generated using hierarchical clustering of all significantly differentially expressed Neurological Genes from individual biological replicates of 5-week-old SHRSP and WKY animals. The relative expression of each gene is represented by colour intensity, where red is up and green is down-regulated in (a) 79 genes from the frontal region and (b) 48 genes identified in the mid-coronal region.
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fig01: Heat maps were generated using hierarchical clustering of all significantly differentially expressed Neurological Genes from individual biological replicates of 5-week-old SHRSP and WKY animals. The relative expression of each gene is represented by colour intensity, where red is up and green is down-regulated in (a) 79 genes from the frontal region and (b) 48 genes identified in the mid-coronal region.

Mentions: Ingenuity Pathway Analysis of all 452 differentially expressed genes at 5 weeks showed that these involved several functional pathways (Table 1), many of which remained affected at 16 and 21 weeks (Table 2). A common feature in both brain regions was the striking over-representation of genes for ‘neurological disease’ (Figure 1) particularly those involved in encephalopathy, stroke, depression and blood brain barrier leakage (Table 3; further details in Tables S1 and S2).


Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.

Bailey EL, McBride MW, Beattie W, McClure JD, Graham D, Dominiczak AF, Sudlow CL, Smith C, Wardlaw JM - Neuropathol. Appl. Neurobiol. (2014)

Heat maps were generated using hierarchical clustering of all significantly differentially expressed Neurological Genes from individual biological replicates of 5-week-old SHRSP and WKY animals. The relative expression of each gene is represented by colour intensity, where red is up and green is down-regulated in (a) 79 genes from the frontal region and (b) 48 genes identified in the mid-coronal region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260148&req=5

fig01: Heat maps were generated using hierarchical clustering of all significantly differentially expressed Neurological Genes from individual biological replicates of 5-week-old SHRSP and WKY animals. The relative expression of each gene is represented by colour intensity, where red is up and green is down-regulated in (a) 79 genes from the frontal region and (b) 48 genes identified in the mid-coronal region.
Mentions: Ingenuity Pathway Analysis of all 452 differentially expressed genes at 5 weeks showed that these involved several functional pathways (Table 1), many of which remained affected at 16 and 21 weeks (Table 2). A common feature in both brain regions was the striking over-representation of genes for ‘neurological disease’ (Figure 1) particularly those involved in encephalopathy, stroke, depression and blood brain barrier leakage (Table 3; further details in Tables S1 and S2).

Bottom Line: We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats.All were present at age 5 weeks thus predating blood pressure elevation. 'Neurological' and 'inflammatory' pathways were more affected than 'vascular' functional pathways.Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD.

View Article: PubMed Central - PubMed

Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.

Show MeSH
Related in: MedlinePlus