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bioRxiv · 10.1101/2020.11.11.377721

Chirality-dependent anti-inflammatory effect of glutathione after spinal cord injury

Kim, S. J.·Ko, W.-K.·Han, G. H.·Lee, D.·Lee, Y.·Sheen, S. H.·Hong, J. B.·Sohn, S.
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Abstract

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared to that in L-GSH-treated rats (***p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared to those outcomes in L-GSH-treated rats (**p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial scar via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared to L-GSH (***p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (***p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.

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Kim, S. J., Ko, W.-K., Han, G. H., Lee, D., Lee, Y., Sheen, S. H., Hong, J. B., Sohn, S.. 2020-11-12. Chirality-dependent anti-inflammatory effect of glutathione after spinal cord injury. https://doi.org/10.1101/2020.11.11.377721

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