Abstract
BackgroundSpinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems. Unfortunately, few effective and safe treatments are known to relieve the damages of SCI. Nanomedicines are used for the treatment of SCI with relatively few side effects, but only depending on the delivery of additional drugs, which increase complexity to the treatment. Considering the urgent need for saving SCI patients, it is important to develop promising nanobiotechnology for relieving their pains.MethodsThe clinical survey was used to investigate SCI patients, thereafter the therapy plan was designed. The receiver-operating characteristics (ROC) curves of the prediction model were built to find symptoms after SCI. The treatment plan (i.e. immunosuppressive strategy) was designed by manufacturing therapies based on gold nanoclusters (AuNCs). The response of the immune cells (macrophages) was studied accordingly. The western blot, reactive oxygen species (ROS) activity assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-qPCR), and immunochemical staining were used for evaluation of the in vivo and in vitro therapeutic effects.ResultsWe found increased monocytes/macrophages (M/Ms) levels in 114 SCI subjects (44.7% with severe SCI complications) by the clinical survey. Additionally, the enhanced macrophage level was found to be closely related to the walking disorder after SCI. Since macrophages were central effector cells of the immune system, we assumed that the immune-suppressing strategies could be used for SCI therapy. Thereafter, AuNCs were stabilized by dihydrolipoic acid (DHLA) enantiomers (including DL-DHLA, R-DHLA; A racemic mixture (R and S) was denoted as DL; R and S refer to Rectus and Sinister), obtaining DL-DHLA-AuNCs and R-DHLA-AuNCs, respectively. In addition, zinc-modified DL-DHLA and R-DHLA stabilized AuNCs (i.e., DL-DHLA-AuNCs-Zn and R-DHLA-AuNCs-Zn) were investigated. Among these AuNCs, R-DHLA-AuNCs-Zn showed the most remarkable therapeutic effect for promoting the polarization of pro-inflammatory macrophages and reducing neuronal ROS-induced apoptosis and inflammation in vitro and in vivo; the lesion size was decreased and the survival rate of ventral neurons is higher.ConclusionsR-DHLA-AuNCs-Zn have comprehensive therapeutic capabilities, especially the immune-suppressing effects for the therapy of SCI, which is promising to relieve the pain or even recover SCI for the patients.Graphical abstract
Highlights
Spinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems
Acute SCI patients had significantly enhanced white blood cell levels (P < 0.05), neutrophils levels (P < 0.05), and monocyte levels (P < 0.05) compared to the control group (Table 1). It had no significant difference in subjects with sex, age, and ASIA in patients compared to the control group (Additional file 1: Table S2)
It was found that the M/Ms level had a close relationship with the walking ability (area under the curve (AUC) = 0.6514, 95% confidence interval 0.807– 0.996, p < 0.0001) (Fig. 1a) after SCI
Summary
Spinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems. Few effective and safe treatments are known to relieve the damages of SCI. A spinal cord injury (SCI), i.e., damage to the spinal cord or nerves at the end of the spinal canal, causes continuous neuroinflammation in the epicenter and surrounding. Steroid pulse therapy and neurotrophic rehabilitation relieve spinal cord ischemia, hypoxia and promote motor function. These strategies have side effects such as the highfrequency treatment. It has been reported that monocytes/macrophages (M/Ms) gather in the lesion after SCI, the injured spinal cord predominantly exists M1 cytotoxic M/Ms [1, 3]. Exploring why the microenvironment induced by SCI plays a vital role in stimulating the polarization of M1, which is important for the establishment of new neuroprotective therapies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
