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Introduction: Spinal cord injury (SCI) is a serious clinical disorder, which involves the patient’s family as well as the community. After sever SCI, astrocytes of the central nervous system become reactive astrocytes, and produce glial scar which is a major obstacle to axons regeneration in the spinal cord. However, some studies have confirmed a spontaneous partial locomotor recovery in injured animals in the course of time and without any therapeutic interventions. Thus, in this study, locomotor function of animals with SCI was assessed to determine the exact scope of such a recovery through BBB (Basso, Bresnahan and Beattie) locomotor test during 20 weeks. Materials and Methods: In this research, 18 adult male Wistar rats were used and randomly divided into 3equale groups: the normal control, the sham, the injured. Animals in the normal control group did not received any intervention, but for the sham and injured groups, laminectomy and contusion model in segment T10 of spinal cord were accomplished, respectively. Locomotor improvement of animals in all the groups was evaluated for 20 weeks. Findings: According to our investigation, comparison of the results of locomotor assessment of the second week against that of the 20th week of the spinal cord injured group without treatment demonstrated a partial locomotor recovery, since the BBB score of lesion in these animals was 1.4 in the second week and reached up to 16 in the Twentieth week. Discussion & Conclusion: Our Results showed that spontaneous locomotor recovery in animals with spinal cord defects increases after 20 weeks (from 16 21 score) in the course of time and without any therapeutic interventions.

Abstract Complete transected spinal cord injury (SCI) severely influences the quality of life and mortality rates of animals and patients. In the past decade, many simple and combinatorial therapeutic treatments have been tested in improving locomotor function in animals with this extraordinarily challenging SCI. The potential mechanism for promotion of locomotor function relies either on direct motor axon regeneration through the lesion gap or indirect neuronal relay bridging to functionally reconnect transected spinal stumps. In this review, we first compare the advantages and problems of complete transection SCI animal models with other prevailing SCI models used in motor axon regeneration research. Next, we enumerate some of the popular bio-scaffolds utilized in complete SCI repair in the last decade. Then, the current state of motor axon regeneration as well as its role on locomotor improvement of animals after complete SCI is discussed. Last, the current approach of directing endogenous neuronal relays formation to achieve motor function recovery by well-designed functional bio-scaffolds implantation in complete transected SCI animals is reviewed. Although facilitating neuronal relays formation by bio-scaffolds implantation appears to be more practical and feasible than directing motor axon regeneration in promoting locomotor outcome in animals after complete SCI, there are still challenges in neuronal relays formation, maintaining and debugging for spinal cord regenerative repair. [ABSTRACT FROM AUTHOR]

Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

Transplantation of somatic cells, including bone marrow stromal cells (BMSCs), bone marrow mononuclear cells (BMNCs), and choroid plexus epithelial cells (CPECs), enhances the outgrowth of regenerating axons and promotes locomotor improvements. They are not integrated into the host spinal cord, but disappear within 2-3 weeks after transplantation. Regenerating axons extend at the spinal cord lesion through the astrocyte-devoid area that is filled with connective tissue matrices. Regenerating axons have characteristics of peripheral nerves: they are associated with Schwann cells, and embedded in connective tissue matrices. It has been suggested that neurotrophic factors secreted from BMSCs and CPECs promote “intrinsic” ability of the spinal cord to regenerate. Transplanted Schwann cells survive long-term, and are integrated into the host spinal cord, serving as an effective scaffold for the outgrowth of regenerating axons in the spinal cord. The disadvantage that axons are blocked to extend through the glial scar at the border of the lesion is overcome. Schwann cells have been approved for clinical applications. Neural stem/progenitor cells (NSPCs) survive long-term, proliferate, and differentiate into glial cells and/or neurons after transplantation. No method is available at present to manipulate and control the behaviors of NPSCs to allow them to appropriately integrate into the host spinal cord. NPSP transplantation is not necessarily effective for locomotor improvement.

We identified a suitable biomatrix that improved axon regeneration and functional outcome after partial (moderate) and complete (severe) chronic spinal cord injury (SCI) in rat. Five weeks after dorsal thoracic hemisection injury the lesion scar was resected via aspiration and the resulting cavity was filled with different biopolymers such as Matrigel™, alginate-hydrogel and polyethylene glycol 600 (PEG) all of which have not previously been used as sole graft-materials in chronic SCI. Immunohistological staining revealed marked differences between these compounds regarding axon regeneration, invasion/elongation of astrocytes, fibroblasts, endothelial and Schwann cells, revascularization, and collagen deposition. According to axon regeneration-supporting effects, the biopolymers could be ranked in the order PEG > > alginate-hydrogel > Matrigel™. Even after complete chronic transection, the PEG-bridge allowed long-distance axon regeneration through the grafted area and for, at least, 1 cm beyond the lesion/graft border. As revealed by electron microscopy, bundles of regenerating axons within the matrix area received myelin ensheathment from Schwann cells. The beneficial effects of PEG-implantation into the resection-cavity were accompanied by long-lasting significant locomotor improvement over a period of 8 months. Following complete spinal re-transection at the rostral border of the PEG-graft the locomotor recovery was aborted, suggesting a functional role of regenerated axons in the initial locomotor improvement. In conclusion, scar resection and subsequent implantation of PEG into the generated cavity leads to tissue recovery, axon regeneration, myelination and functional improvement that have not been achieved before in severe chronic SCI.

The effects of multiple injection of bone marrow mononuclear cells (BMNCs) on spinal cord injury (SCI) were compared with those of single injection in rats. BMNCs separated by density-gradient centrifugation from a bone marrow perfusate were injected three times (once weekly) through the cerebrospinal fluid (CSF) via the fourth ventricle, and the locomotor improvement and tissue recovery, including axonal regeneration, were compared with those of single injection. While the single-injection group showed a steep elevation of the Basso-Beattie-Bresnahan (BBB) score 1 week after transplantation, the multiple-injection group maintained a similar steep elevation for 2 weeks after transplantation, and the BBB scores of the multiple-injection group remained thereafter at a level approximately 2-3 points higher than those of the single-injection group until the end of the experiment. There were significant differences between the single- and multiple-injection groups at 3, 4, and 8 weeks after transplantation. The difference in BBB scores at 8 weeks after transplantation suggested that there was a marked difference in the quality of locomotor behaviors between the single-and multiple-injection groups at this stage. An extensive outgrowth of regenerating axons through the astrocyte-devoid areas and a marked reduction of cavity formation were found in both the single- and multiple-injection groups. There were, however, no significant differences in the density of regenerating axons or volumes of cavities between the single- and multiple-injection groups. These results showed that although tissue recoveries were similar between single and multiple injection, the multiple injection of BMNCs was more beneficial for locomotor improvement than single injection for the treatment of SCI. Considering the technically simple and low-cost procedures for the preparation and injection of BMNCs, multiple injection of BMNCs by lumbar puncture has an advantage over single injection on clinical application. [ABSTRACT FROM AUTHOR]

Abstract: We identified a suitable biomatrix that improved axon regeneration and functional outcome after partial (moderate) and complete (severe) chronic spinal cord injury (SCI) in rat. Five weeks after dorsal thoracic hemisection injury the lesion scar was resected via aspiration and the resulting cavity was filled with different biopolymers such as Matrigel™, alginate-hydrogel and polyethylene glycol 600 (PEG) all of which have not previously been used as sole graft-materials in chronic SCI. Immunohistological staining revealed marked differences between these compounds regarding axon regeneration, invasion/elongation of astrocytes, fibroblasts, endothelial and Schwann cells, revascularization, and collagen deposition. According to axon regeneration-supporting effects, the biopolymers could be ranked in the order PEG>>alginate-hydrogel>Matrigel™. Even after complete chronic transection, the PEG-bridge allowed long-distance axon regeneration through the grafted area and for, at least, 1cm beyond the lesion/graft border. As revealed by electron microscopy, bundles of regenerating axons within the matrix area received myelin ensheathment from Schwann cells. The beneficial effects of PEG-implantation into the resection-cavity were accompanied by long-lasting significant locomotor improvement over a period of 8months. Following complete spinal re-transection at the rostral border of the PEG-graft the locomotor recovery was aborted, suggesting a functional role of regenerated axons in the initial locomotor improvement. In conclusion, scar resection and subsequent implantation of PEG into the generated cavity leads to tissue recovery, axon regeneration, myelination and functional improvement that have not been achieved before in severe chronic SCI. [Copyright &y& Elsevier]

Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety., Competing Interests: Conflicts of Interest: None declared.

Transplantation of somatic cells, including bone marrow stromal cells (BMSCs), bone marrow mononuclear cells (BMNCs), and choroid plexus epithelial cells (CPECs), enhances the outgrowth of regenerating axons and promotes locomotor improvements. They are not integrated into the host spinal cord, but disappear within 2-3 weeks after transplantation. Regenerating axons extend at the spinal cord lesion through the astrocyte-devoid area that is filled with connective tissue matrices. Regenerating axons have characteristics of peripheral nerves: they are associated with Schwann cells, and embedded in connective tissue matrices. It has been suggested that neurotrophic factors secreted from BMSCs and CPECs promote "intrinsic" ability of the spinal cord to regenerate. Transplanted Schwann cells survive long-term, and are integrated into the host spinal cord, serving as an effective scaffold for the outgrowth of regenerating axons in the spinal cord. The disadvantage that axons are blocked to extend through the glial scar at the border of the lesion is overcome. Schwann cells have been approved for clinical applications. Neural stem/progenitor cells (NSPCs) survive long-term, proliferate, and differentiate into glial cells and/or neurons after transplantation. No method is available at present to manipulate and control the behaviors of NPSCs to allow them to appropriately integrate into the host spinal cord. NPSP transplantation is not necessarily effective for locomotor improvement., Competing Interests: Conflicts of Interest: None declared.