The Glial Scar-Monocyte Interplay: A Pivotal Resolution Phase in Spinal Cord Repair
Figure 5
Expression of matrix metalloproteinase 13 by infiltrating monocytes is essential for functional recovery from spinal cord injury.
(A–D) 45D-vaccinated, [wt>wt] or [MMP-13−/−>wt] BM chimeras were subjected to spinal cord injury 8 weeks post transplantation. (A,B) Motor function evaluation was performed according to the BMS. Follow up is shown in A and individual scorings at day 21 are shown in B. Deficiency in MMP-13 resulted in worse motor function (A-Repeated ANOVA; Fbetween-groups(1,16) = 13.4; p<0.0001; B- Student's t-test; ***p<0.001). (C,D) Representative pictures of lesion sites stained for myelin integrity by Luxol-Nissl are presented in C. Lesion size evaluation according to Luxol-Nissl staining is shown in D. Increased lesion size is observed in MMP-13 deficient chimeras (Student's t-test; **p = 0.004). (E–H) [CD11c-DTR>wt] BM chimeric mice were subjected to spinal cord injury 8 weeks post BM transplantation. Four groups were used: one group was left untreated, one group was treated with DTx alone, and the other two groups received DTx in parallel to transfer with DTx-resistant monocytes isolated from either wt or MMP-13 KO mice. (E,F) Motor function evaluation was performed according to the BMS. Follow-up is shown in E and individual scorings at day 14 are shown in F. DTx depletion resulted in worse recovery. While reconstitution with wt monocytes restored lost motor function, replenishment with MMP-13 KO monocytes failed to do so (E-Repeated ANOVA; Fbetween-groups(3,44) = 16.28; p<0.0001; F- ANOVA; F3,39 = 44.15; p<0.0001). (G,H) Representative pictures of lesion sites stained for myelin integrity by Luxol-Nissl, G. Lesion size evaluation according to Luxol-Nissl staining is shown in H (ANOVA; F3,25 = 15.6; p<0.0001). Scale bar; 100 µm.