Inflammatory Pathways in Spinal Cord Injury - International Review of Neurobiology - page 138

A B C D

E F G H

Figure 5.3 (A) Low-magnification image of spinal cord cross-section 14 days after spinal
cord contusion injury double labeled for GFAP and SLPI (L¼lesion). Note the increased
expression of SLPI (green) in areas bordering the lesion and in neurons in the ventral
horn. The area outlined in the box is shown in higher magnification in panels (B - D).
(B - D) Higher magnification shows strong SLPI immunoreactivity (C) in reactive astro-
cytes (B) along the border of the lesion; the merged image with DAPI labeling is shown
in panel (D) (L¼lesion). (E) Low-magnification image of spinal cord cross-section 1 day
postinjury double labeled for neutrophils (antibody 7/4) (red) and SLPI (green). Note also
the SLPI labeling in the ventral horn, which appears to be neurons. (F - H) Higher mag-
nification of the area outlined in the box in panel (E) is shown in (F - H). Some neutrophils
(F) (arrows) are also labeled for SLPI (G); the merged image is shown in panel (H). The
inset in (H) shows higher magnification of the area outlined with the dashed lines show-
ing SLPI labeling in neutrophils. Scale bar in (A and E)¼500 mm, in (D and H)¼100 mm,
inset in H¼25 mm. With permission from Ghasemlou, Bouhy, et al. (2010) .

mice overexpressing SLPI showed improved locomotor recovery between 3
and 10 days postinjury, however, this effect was lost by day 14. Based on this
result, we hypothesized that SLPI may be beneficial in the early phase of SCI
when the expression of proinflammatory mediators (cytokines, proteases,
etc.) are high, while its anti-inflammatory effects may be detrimental to re-
covery at later time-points. We therefore treated wild-type mice daily with
1 m g/g rSLPI by intraperitoneal injection for the first 7 days after SCI and
found improved locomotor recovery starting 3 days after injury and con-
tinuing until the end of the experiment at 28 days ( p < 0.05). Histological
analysis of the spinal cords from rSLPI-treated animals at 28 days revealed
significantly reduced lesion size measured using GFAP-immunoreactivity,