Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury?

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Methylprednisolone (MP) is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury (SCI). Vitamin C (VC) is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells (BMMSCs), as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups: control, SCI (SCI induction by weight-drop method), MP (SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times), VC (SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days), MP + VC (SCI induction, followed by administration of MP and VC as the former), BMMSCs (SCI induction, followed by injection of 3 × 10 ⁶ BMMSCs at the injury site), and BMMSCs + VC (SCI induction, followed by BMMSCs injection and VC administration as the former). Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI.

Related collections

Most cited references 73

Record: found
Abstract: found
Article: not found

The cellular inflammatory response in human spinal cords after injury.

Jennifer Fleming, Michael Norenberg, David A Ramsay … (2006)

Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were 'dead at the scene' or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1-3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil alpha-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1-3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1-3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8(+) lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative enzymes myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate oxidase (gp91(phox)), and of the pro-inflammatory matrix metalloproteinase (MMP)-9, was analysed to determine their potential to cause oxidative and proteolytic damage. Oxidative activity, inferred from MPO and gp91(phox) immunoreactivity, was primarily associated with neutrophils and activated microglia. Phagocytic macrophages had weak or no expression of MPO or gp91(phox). Only neutrophils expressed MMP-9. These data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory 'neuroprotective' strategies should be directed at preventing early neutrophil influx and modifying microglial activation.

0 comments Cited 243 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Oxidative stress in spinal cord injury and antioxidant-based intervention.

H Misra, Xiaoqian Wang, Z Jia … (2012)

Literature review. Spinal cord injury (SCI) remains a major public health issue in developed countries as well as worldwide. The pathophysiology of SCI is characterized by an initial primary injury followed by secondary deterioration. Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress have a significant role in the pathophysiology of SCI. Thus, alleviating oxidative stress may be an effective strategy for therapeutic intervention of SCI. The aim of this review was to describe (i) the sources of ROS as well as the major antioxidant defenses with particular attention being paid to lipid peroxidation; (ii) the biomarkers of oxidative stress in SCI and (iii) the neuroprotective effects of various compounds with antioxidative properties in animal models of SCI. PubMed, one of the most comprehensive biomedical databases, was searched from 1976-2011. All relevant papers were read by title, abstract and full-length article. Oxidative stress is considered a hallmark of injury of SCI. Thus, alleviating oxidative stress may be an effective way of therapeutic intervention of SCI. Two of these agents, the glucocorticoid steroid methylprednisolone and the non-glucocorticoid 21-aminosteroid tirilazad, have been shown to possess significant antioxidant activities and improve recovery of SCI patients in clinical trials. Other promising botanical compounds and their molecular targets and mechanisms of action with regard to potential protection against SCI were also described. These include carotenoids and phenolic compounds. ROS and oxidative stress have a significant role in the pathophysiology of SCI. Alleviating oxidative stress is be an effective strategy for therapeutic intervention of SCI. Extensive research over the past several decades has identified numerous bioactive compounds that have antioxidative stress benefits in animal models of SCI. Thus, continued studies on bioactive compounds with ROS-scavenging capacity may lead to the development of effective antioxidant-based modalities for treating SCI in human subjects.

0 comments Cited 105 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Pharmacological therapy for acute spinal cord injury.

Daniel E Gelb, R J Hurlbert, Nicholas Theodore … (2013)

0 comments Cited 85 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Neural Regen Res

Journal ID (iso-abbrev): Neural Regen Res

Journal ID (publisher-id): NRR

Title: Neural Regeneration Research

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 1673-5374

ISSN (Electronic): 1876-7958

Publication date (Print): December 2017

Volume: 12

Issue: 12

Pages: 2050-2058

Affiliations

[1 ]Department of Histology and Cell Biology, Faculty of Medicine, Banha University, Banha, Egypt

[2 ]Department of Neurosurgery, Faculty of Medicine, Banha University, Banha, Egypt

[3 ]Department of Community Medicine, Faculty of Medicine, Banha University, Banha, Egypt

[4 ]Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Giza, Egypt

[5 ]Department of Surgery and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

[6 ]Department of Surgery, Faculty of Veterinary Medicine, Banha University, Banha, Egypt

[7 ]Department of Medical Physiology, Faculty of Medicine, Banha University, Banha, Egypt

[8 ]Department of Medical Biochemistry, Faculty of Medicine, El Fayoum University, Egyptian, Egypt

Author notes

[* ] Correspondence to: Dina Sabry, dinasabry@ 123456kasralainy.edu.eg .

Author contributions: MME and MzAE designed the study and performed data analysis. NS, MYS, DS and AE were responsible for histological and molecular assessment of the work. MoAE was in charge of statistical analysis. AS and AHHE were responsible for surgical procedure of the experiment. NI assessed physiological and molecular procedures. All authors contribited to writing of the paper and approved the final version of this paper .

Author information

Dina Sabry http://orcid.org/0000-0002-6720-3385

Article

Publisher ID: NRR-12-2050

DOI: 10.4103/1673-5374.221163

PMC ID: 5784354

PubMed ID: 29323045

SO-VID: c656c4ff-d48b-41cb-9d8c-b77e820daa50

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury?

Read this article at

Abstract

Related collections

Gamma Delta T cells

Most cited references 73

The cellular inflammatory response in human spinal cords after injury.

Oxidative stress in spinal cord injury and antioxidant-based intervention.

Pharmacological therapy for acute spinal cord injury.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 209

Cited by 4

Most referenced authors 910