C-176 reduces TBI-induced proinflammatory cytokine response
2h-post injury
To elucidate the effect of C-176 on the neuroinflammatory milieu
post-TBI, gene expression of pro-inflammatory markers intimately related
to the type-I IFN response was measured in the ipsilateral cortex and
striatum region of the brain at 2h and 24h-post TBI (Fig 7).
Administration of C-176 significantly attenuated cortical expression ofCXCL10 2h-post TBI (Fig 7Av) compared to vehicle-treated mice and
did not have a marked effect on cortical expression of the other
pro-inflammatory markers measured (Figure 7Ai-iv,vi). C-176-treated mice
displayed a significant reduction in striatal gene expression of
pro-inflammatory cytokines TNF-α, IL-1β and CXCL10compared to their vehicle-treated counterparts at 2h post-TBI (Fig
7Ai,iii-,v).Vehicle-treated mice 24h post-TBI displayed significantly
elevated expression of IL-1 β, TNF-α and CXCL10 in
both the cortex and the striatum compared to sham (Fig 7i, iii, v).IL-6 and iNOS expression increased in the vehicle-treated
TBI mice in the cortex (Fig 7B ii, iv). C-176 treated mice displayed
significantly increased expression of TNF-α in both the cortex
and the striatum (Fig 7Biii) and CXCL10 in the cortex compared to
sham (Fig 7Bv). No significant difference in the expression of the
pro-inflammatory markers measured was detected between the
vehicle-treated mice and C-176 treated mice 24h-post TBI (Fig 7B).