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Delayed inflammatory mRNA and protein expression after spinal cord injury.

Byrnes KR, Washington PM, Knoblach SM, Hoffman E, Faden AI - J Neuroinflammation (2011)

Bottom Line: As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury.Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma.These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Georgetown University Medical Center, NW, Washington, DC (20057), USA. kbyrnes@usuhs.mil

ABSTRACT

Background: Spinal cord injury (SCI) induces secondary tissue damage that is associated with inflammation. We have previously demonstrated that inflammation-related gene expression after SCI occurs in two waves - an initial cluster that is acutely and transiently up-regulated within 24 hours, and a more delayed cluster that peaks between 72 hours and 7 days. Here we extend the microarray analysis of these gene clusters up to 6 months post-SCI.

Methods: Adult male rats were subjected to mild, moderate or severe spinal cord contusion injury at T9 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury and processed for microarray analysis and protein expression.

Results: Anchor gene analysis using C1qB revealed a cluster of genes that showed elevated expression through 6 months post-injury, including galectin-3, p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these genes occurred primarily in microglia/macrophage cells and was confirmed at the protein level using both immunohistochemistry and western blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury. Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma.

Conclusions: These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss.

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Related in: MedlinePlus

Graphical representation of the expression of the delayed-expression cluster of genes. A subset of genes in the delayed-expression cluster, including C1qB (C1q), CD53, p22PHOX (Cyba), and galectin-3 (Lgals3) are graphed to demonstrate the fold expression change over naïve from 4 hr to 6 months post-injury. Note the similar pattern of expression within the group as well as between injury severities (Moderate, Mild, and Severe). Note also that expression of genes in the delayed-expression cluster remained up-regulated (above a 2 fold increase) through 6 months post-injury.
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Figure 2: Graphical representation of the expression of the delayed-expression cluster of genes. A subset of genes in the delayed-expression cluster, including C1qB (C1q), CD53, p22PHOX (Cyba), and galectin-3 (Lgals3) are graphed to demonstrate the fold expression change over naïve from 4 hr to 6 months post-injury. Note the similar pattern of expression within the group as well as between injury severities (Moderate, Mild, and Severe). Note also that expression of genes in the delayed-expression cluster remained up-regulated (above a 2 fold increase) through 6 months post-injury.

Mentions: The 'delayed expression' cluster, identified using the C1qB anchor gene, was not up-regulated until 24 to 48 hours after injury, but then remained up-regulated throughout the study, up to 6 months post-injury (Table 1, Figure 1, 2). Expression of genes in this cluster peaked between 7 and 28 days post-injury, and remained elevated in comparison to sham-injured rats through 6 months post-injury. This expression profile was similar regardless of injury severity. Twenty-three genes were found to be temporally correlated, with an r2 value of greater than 0.99 in this cluster (Table 3).


Delayed inflammatory mRNA and protein expression after spinal cord injury.

Byrnes KR, Washington PM, Knoblach SM, Hoffman E, Faden AI - J Neuroinflammation (2011)

Graphical representation of the expression of the delayed-expression cluster of genes. A subset of genes in the delayed-expression cluster, including C1qB (C1q), CD53, p22PHOX (Cyba), and galectin-3 (Lgals3) are graphed to demonstrate the fold expression change over naïve from 4 hr to 6 months post-injury. Note the similar pattern of expression within the group as well as between injury severities (Moderate, Mild, and Severe). Note also that expression of genes in the delayed-expression cluster remained up-regulated (above a 2 fold increase) through 6 months post-injury.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198932&req=5

Figure 2: Graphical representation of the expression of the delayed-expression cluster of genes. A subset of genes in the delayed-expression cluster, including C1qB (C1q), CD53, p22PHOX (Cyba), and galectin-3 (Lgals3) are graphed to demonstrate the fold expression change over naïve from 4 hr to 6 months post-injury. Note the similar pattern of expression within the group as well as between injury severities (Moderate, Mild, and Severe). Note also that expression of genes in the delayed-expression cluster remained up-regulated (above a 2 fold increase) through 6 months post-injury.
Mentions: The 'delayed expression' cluster, identified using the C1qB anchor gene, was not up-regulated until 24 to 48 hours after injury, but then remained up-regulated throughout the study, up to 6 months post-injury (Table 1, Figure 1, 2). Expression of genes in this cluster peaked between 7 and 28 days post-injury, and remained elevated in comparison to sham-injured rats through 6 months post-injury. This expression profile was similar regardless of injury severity. Twenty-three genes were found to be temporally correlated, with an r2 value of greater than 0.99 in this cluster (Table 3).

Bottom Line: As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury.Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma.These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Georgetown University Medical Center, NW, Washington, DC (20057), USA. kbyrnes@usuhs.mil

ABSTRACT

Background: Spinal cord injury (SCI) induces secondary tissue damage that is associated with inflammation. We have previously demonstrated that inflammation-related gene expression after SCI occurs in two waves - an initial cluster that is acutely and transiently up-regulated within 24 hours, and a more delayed cluster that peaks between 72 hours and 7 days. Here we extend the microarray analysis of these gene clusters up to 6 months post-SCI.

Methods: Adult male rats were subjected to mild, moderate or severe spinal cord contusion injury at T9 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury and processed for microarray analysis and protein expression.

Results: Anchor gene analysis using C1qB revealed a cluster of genes that showed elevated expression through 6 months post-injury, including galectin-3, p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these genes occurred primarily in microglia/macrophage cells and was confirmed at the protein level using both immunohistochemistry and western blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury. Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma.

Conclusions: These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss.

Show MeSH
Related in: MedlinePlus