Glutathione in the Pons Is Associated With Clinical Status Improvements in Subacute Spinal Cord Injury

Abstract

Objectives: In spinal cord injury (SCI), the primary mechanical injury is followed by secondary sequelae that develop over the subsequent months and manifests in biochemical, functional, and microstructural alterations, at the site of direct injury but also in the spinal cord tissue above and below the actual lesion site. Noninvasive magnetic resonance spectroscopy (MRS) can be used to assess biochemical modulation occurring in the secondary injury phase, in addition to and supporting conventional MRI, and might help predict and improve patient outcome. In this article, we aimed to examine the metabolic levels in the pons of subacute SCI by means of in vivo proton MRS at 3 T and explore the association to clinical scores. Materials and Methods: In this prospective study, between November 2015 and February 2018, single-voxel short-echo MRS data were acquired in healthy controls and in SCI subjects in the pons once during rehabilitation. Besides the single-point MRS examination, in addition, in participants with SCI, the clinical status (ie, motor, light touch, and pinprick scores) was assessed twice: (1) around the MRS session (approximately 10 weeks postinjury) and (2) before discharge (at approximately 9 months postinjury). The group differences were assessed with Kruskal-Wallis test, the post hoc comparison was assessed with Wilcoxon rank sum test, and the clinical correlations were conducted with Spearman rank correlation test. Bayes factor calculations completed the statistical part providing relevant evidence values. Results: Twenty healthy controls (median age, 50 years; interquartile range, 41-55 years; 18 men) and 18 subjects with traumatic SCI (median age, 50 years; interquartile range, 32-58 years; 16 men) are included. Group comparison showed an increase of total N-acetylaspartate and combined glutamate and glutamine levels in complete SCI and a reduction of total creatine in incomplete paraplegic SCI. The proton MRS-based glutathione levels at baseline correlate to the motor score improvement during rehabilitation in incomplete subacute SCI. Conclusions: This exploratory study showed an association of the metabolite concentration of glutathione in the pons assessed at approximately 10 weeks after injury with the improvements of the motor score during the rehabilitation. Pontine glutathione levels in subjects with traumatic subacute incomplete SCI acquired remote from the injury site correlate to clinical score and might therefore be beneficial in the rehabilitation assessments.

Glutathione effect on functional and histological recovery after spinal cord injury in rats

“…Our study used the standardized model to investigate the effects of GSH, an antioxidant, in the experimental spinal cord injury. 26 , 27 , 28 , 29 , 30 GSH plays an important role in controlling reactive oxygen species that arise after spinal cord injury and are responsible for the propagation of tissue injury. Different studies demonstrate the GSH in its reduced form when there is injury by oxygen free radicals in different cell types, being even more important in neuronal cells.…”

“…The secondary cellular events that follow the initial traumatic mechanical injury contribute to the propagation of tissue damage associated with cell damage caused by the release of oxygen free radicals and the reduction of mechanisms and substances responsible for maintaining cellular homeostasis, highlighting the role of GSH in its reduced form. 29 , 30 Furthermore, associated with oxidative stress and inflammatory reaction, the harmful effect of vascular and ischemic disorders and homeostasis in this propagation of secondary damage is added, which can also be addressed with different therapeutic strategies, making the approach to spinal cord trauma increasingly multifactorial. 31 , 32 , 33 …”

Avaliação do efeito da glutationa na recuperação funcional e histológica após lesão medular experimental em ratos

“…Wyss et al 123 (2022) examinaram os níveis dos metabólitos da glutationa na ponte cerebral na lesão medular incompleta subaguda em humanos e compararam com controles saudáveis. Encontraram uma associação entre a concentração de metabólitos de glutationa na ponte cerebral e melhora dos escores motores de reabilitação com 10 semanas da lesão.…”