Aldynoglia are growth-promoting cells with a morphology similar to radial glia and share properties and markers with astrocytes and Schwann cells. They are distributed in several locations throughout the adult central nervous system, where the cells of the aldynoglia interact and respond to the signals of the immune cells. After spinal cord injury (SCI), the functions of resident aldynoglia, identified as ependymocytes, tanycytes, and ependymal stem cells (EpSCs) of the spinal cord are crucial for the regeneration of spinal neural tissue. These glial cells facilitate axonal regrowth and remyelination of injured axons. Here, we review the influence of M1 or M2 macrophage/microglia subpopulations on the fate of EpSCs during neuroinflammation and immune responses in the acute, subacute, and chronic phases after SCI.

Immunization with neural derived peptides (INDP) as well as scar removal—separately—have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α′-dipyridyl. During the chronic injury stage, two experiments were undertaken. The first experiment was aimed at testing the therapeutic effect of INDP combined with scar removal. Sixty days after therapeutic intervention, the expression of genes encoding for TNFα, IFNγ, IL4, TGFβ, BDNF, IGF1, and GAP43 was evaluated at the site of injury. Tyrosine hydroxylase and 5-hydroxytryptamine positive fibers were also studied. Locomotor evaluations showed a significant recovery in the group treated with scar removal + INDP. Moreover; this group presented a significant increase in IL4, TGFβ, BDNF, IGF1, and GAP43 expression, but a decrease of TNFα and IFNγ. Also, the spinal cord of animals receiving both treatments presented a significant increase of serotonergic and catecholaminergic fibers as compared to other the groups. The second experiment compared the results of the combined approach versus INDP alone. Rats receiving INDP likewise showed improved motor recovery, although on a lesser scale than those who received the combined treatment. An increase in inflammation and regeneration-associated gene expression, as well as in the percentage of serotonergic and catecholaminergic fibers was observed in INDP-treated rats to a lesser degree than those in the combined therapy group. These findings suggest that INDP, both alone and in combination with scar removal, could modify the non-permissive microenvironment prevailing at the chronic phase of SCI, providing the opportunity of improving motor recovery.

Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides (INDP), inhibition of glial scar formation (dipyridyl: DPY), as well as the use of biocompatible matrix (fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells (MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord (hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy (DPY+ INDP + FG + MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy (DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee (approval No. 178544; CSNBTBIBAJ 090812960) on August 15, 2016.

Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model.