Experimental autoimmune encephalomyelitis and age-related correlations of NADPH oxidase, MMP-9, and cell adhesion molecules: The increased disease severity and blood–brain barrier permeability in middle-aged mice

• EAE severity and BBB permeability were increased in 6 M-EAE.
• NADPH oxidase activity, MMP-9 activity, ICAM-1, and VCAM-1 were up-regulated and correlated with age and EAE effects.
• Strong correlations between NADPH oxidase and other factors in CNS tissues were observed in 6 M-EAE.
• Immunological changes by increased age definitely affected EAE pathogenesis.
• NADPH oxidase had a leading role in EAE development of middle-aged mice.

The aim of the present study was to investigate effect of two different ages (6 weeks [6 W] vs. 6 months [6 M]) on blood–brain barrier (BBB) disruption in EAE and evaluate the expression and correlations of NADPH oxidase, MMP-9, ICAM-1, and VCAM-1 following increased age and EAE induction. Higher disease severity was observed in 6 M-EAE than 6 W-EAE. The four factors were significantly elevated and correlated in 6 M-EAE. BBB permeability increased with statistically significant interaction between age and EAE effects. We suggest strong correlations between NADPH oxidase and the other factors play important roles in increased BBB disruption and EAE susceptibility in middle-aged mice.

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