Figure 8: Schematic model of T1-regulated GAG balance after SCI.

(a) Summary of the results on SCI recovery. In WT (uppermost) mice, CS (dark pink) production was elevated in the reactive astrocytes (star-like form in blue), and thick scars (black)³, which inhibited axon regeneration, formed; consequently, very few regenerating axons could migrate to areas past the SCI lesion. In contrast, in T1KO mice (middle), CS production was reduced and the scars were smaller than those in WT mice. In addition, HS (green) expression was high in T1KO neurons, and the number of regrowing or sprouting axons was higher than that in WT. Although ChABC-treated mice (ChABC; lowermost) had less CS than did WT or T1KO, they had larger scars than T1KO mice, and they did not overproduce HS; therefore, axonal regeneration was reduced and restricted relative to that in T1KO. WT and ChABC-treated mice, unlike T1KO mice, experienced only baseline levels of HS synthesis after SCI; these baseline levels could not promote recovery from SCI. (b) Possible biochemical mechanism that promotes better recovery from SCI in TIKO mice²⁶. In WT, T1 is upregulated in reactive astrocytes after SCI; however, Ext1 and Ext2, which are genes with putative ‘axon growth-promoting activity/potential’, are upregulated in neurons of T1KO mice, and T1 is not expressed (minus in red); consequently, HS, rather than CS, accumulates around T1KO neurons. As a result, the amount of CS decreases and that of HS increases, and this shift in the CS-HS balance promotes axon regrowth³⁹. As increases in HS and decreases in CS persist, the potential for axon growth is elevated.