scholarly journals Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model

2021 ◽  
Vol 14 (8) ◽  
pp. 792
Author(s):  
Seong-Jun Kim ◽  
Wan-Kyu Ko ◽  
Gong-Ho Han ◽  
Daye Lee ◽  
Yuhan Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Potential ◽  
Specific Interaction ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Secondary Damage ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Pro Inflammatory Cytokines

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. 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 with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with 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.

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

2020 ◽  
Author(s):  
Seong Jun Kim ◽  
Wan-Kyu Ko ◽  
Gong Ho Han ◽  
Daye Lee ◽  
Yuhan Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Potential ◽  
Mapk Signaling ◽  
Glial Scar ◽  
Mitogen Activated Protein Kinase ◽  
Secondary Damage ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Pro Inflammatory Cytokines

AbstractNeuroinflammation 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.

scholarly journals Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) Contributes to Secondary Damage after Spinal Cord Injury

2010 ◽  
Vol 30 (41) ◽  
pp. 13750-13759 ◽  
Author(s):  
N. Ghasemlou ◽  
R. Lopez-Vales ◽  
C. Lachance ◽  
T. Thuraisingam ◽  
M. Gaestel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Secondary Damage ◽  
Cord Injury ◽  
Mitogen Activated Protein

scholarly journals Leucine rich repeats and calponin homology domain containing 1 inhibits microglia-mediated neuroinflammation in a rat traumatic spinal cord injury model

2020 ◽  
Author(s):  
Wen-Kai Chen ◽  
Lin-Juan Feng ◽  
Qiao-Dan Liu ◽  
Qing-Feng Ke ◽  
Pei-Ya Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Cytokines ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Neuron Death ◽  
Microglial Polarization ◽  
Cord Injury ◽  
Pro Inflammatory Cytokines

Abstract Background Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. Methods To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture, and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. Results We found that LRCH1 was down-regulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. Conclusion Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI, and provides clues for developing novel therapeutic approaches against SCI.

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