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CHAPTER 1 due to neural plasticity (Onifer et al., 2011). However, these training strategies have not been shown to help the loss of sensation (Larson and Dension, 2013). Apart from these, electrical or magnetic brain stimulations, transcutaneous electrical nerve simulations, acupuncture and self- hypnosis have been investigated for alleviating pain associated with spinal cord injury (reviewed in Boldt et al., 2014). However, none has proven to be significantly beneficial in terms of pain relief. 1.1.2.4 Novel therapies Since current treatment strategies cannot provide long-term functional benefits following spinal cord injury, a variety of novel strategies have been investigated with the aim to repair the injured spinal cord. The two main areas of research are cellular therapy and molecular therapy. Most of these cells target the secondary damage following the injury to improve regeneration. Cellular therapy Cellular therapy involves the transplantation of different cells into the injured spinal cord. These cells mainly fall into two categories: stem cells and glial cells (reviewed in Tetzlaff et al., 2011). These cells are either directly injected into the injured spinal cord or with some aid such as hydrogels (Assuncao-Silva et al., 2015). Stem cells, including neural, mesenchymal, embryonic and induced pluripotent types, may be injected into the spinal cord directly or after in vitro pre-differentiation. These cells are capable of differentiating into neurons and glial cells. They are applied so that the damaged/lost cells in the spinal cord can be replaced. However, unclear cellular mechanisms, safety issues, and ethical concerns have halted the progress of stem cell therapy in clinical trials (Silva et al., 2014). The other cells used in cell transplantation are glial cells, which include olfactory ensheathing cells and Schwann cells. These cells are injected into the spinal cord to provide a better cellular environment for regeneration. Olfactory ensheathing cells and Schwann cells are known to assist axonal regeneration through removal of axonal debris, secretion of neurotrophic factors, and production of extracellular matrix (Oudega and Xu, 2006). More preclinical studies are required due to limited efficacy and evidence in clinical trials. Molecular therapy Molecular therapy involves the administration of compounds that could potentially improve recovery by altering the inflammatory response, blocking inhibitors, and promoting generation. Unfortunately, many of these therapies exhibit inconsistent efficacy and contradictory results. Molecules such as interleukin-10, minocycline, and riluzole have been demonstrated to alter inflammation; they have thus been used to treat spinal cord injury. Interleukin-10 has been tested in animal models due to its ability to inhibit the production of TNFα (Bethea et al., 1999). Minocycline, currently in phase III trial, is believed to inhibit microglial activation and prevent apoptosis (Heo et al., 2006; Stirling et al., 2005). Riluzole, also in phase III trial, is a sodium channel blocker, which indirectly stimulates glutamate uptake and reduces neurotoxicity (Azbill 15PDF Image | Effects of Red Light Treatment on Spinal Cord Injury
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