Strategies to Repair Spinal Cord Injuries: Single Vs. Combined Treatments
Paraplegia [Working Title]
Several experimental strategies have been developed in past years for the repair of damages evoked in axons, myelin, and motor functions by spinal cord injuries. This chapter briefly reviews some of such strategies. On the one hand, it examines individual procedures, such as: tissue or cell transplants (i.e. evolving cells of the olfactory glia or mesenchymal cells), implants of biomaterials (fibrine and chitosan), application of enzymes (chondroitinase and ChABC), growth factors (brain-derived
... tors (brain-derived neurotrophic factor, BDNF; neurotrophin-3, NT-3; or glial-derived neurotrophic factor, GDNF), and drugs (myocyclines or riluzole) among others, that induce different recovery degrees in axonal regeneration, myelination, and motor performance in experimental animals. On the other hand, it also examines the recent strategy of combining some of the previous experimental procedures to potentialize the positive effects evoked by each one in experimentally spinal cord lesioned animals and explores the possible use of this strategy in future preclinical research for the treatment of spinal cord lesions. Paraplegia 2 NgR1 is anchored to its GPI protein, in its intracellular domain, different co-receptors are activated that favor the activation of axonal inhibition signaling. In this activation, the two molecules P75 (molecule belonging to the TNF receptor) and TOY (LINGO-1) are involved. Activation of this co-receptor complex favors the activation of a RhoA kinase, which activates another ROCK kinase, in turn promoting the activation of LIM. This LIM kinase can activate the cofilin factor, thus causing the collapse of the axonal cone and depolymerization of the actin filaments [3, 4]. On the other hand, the glial reaction, which happens after the injury, promotes the recruitment of the microglia, oligodendrocyte precursors, meninges cells, and astrocytes in their reactive form at the site of the injury . The result of this cell migration is the formation of a physical barrier, the fibroglial scar, which has the function of isolating the area of injury from the rest of the tissue, secreting factors that cause axonal growth to be inhibited in order to avoid aberrant connectivity. The factors that are present in the glial scar are: tenacines, semaphorins, ephrines, and chondroitin sulfate proteoglycans . These molecules that are expressed from the extracellular matrix after a TSCI promote inhibition of axonal and neuritic growth as well as collapse of the axonal cone [6, 7]. The activation of all these molecules is due to an RHO-(RhoA) kinase; by activating the RhoA signaling pathway, it causes a decrease in the activity of RAC1 kinase, through binding to the PTPα receptor (transmembrane protein tyrosine phosphatase), in addition to LAR and NGR1 and 3 leukocyte-related phosphatase. This causes RhoA to be phosphorylated from Rho-GDP to Rho-GTP, activating ROCK kinase, thereby promoting inhibition of axonal growth (Figure 1 ; [6, 7]).