*4.1.2 Resveratrol*

Resveratrol is a natural polyphenolic compound that has exhibited beneficial health properties as well as antioxidant, anti-inflammatory, and antitumor effects. Resveratrol exerts a neuroprotective effect by regulating apoptosis [118]. Studies have shown that the anti-inflammatory effects of resveratrol are mediated mainly by sirtuin (SIRT) 1 [119, 120]. Resveratrol enhances locomotor recovery [121–123]. Furthermore, resveratrol increases nuclear factor erythroid 2-related factor (Nrf-2) activation, providing antioxidant effects [121]. Further investigation is needed in order to provide more evidence about the efficacy of this treatment.


**169**

**Table 4.**

*Stem cell therapy in spinal cord injury.*

BMSCs + IGF-1

BMSCs + OECs

*Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art*

The use of growth factors like BDNF, transforming growth factor-β (TGF-β), and insulin-like growth factor-1 (IGF-1) as a therapy to improve morphological and behavioral outcomes after SCI has been topic of study of many investigations.

BDNF exerts a relevant function in the repair of neural tissue and plasticity in CNS [124, 125]. Nevertheless, recent studies have also shown that BDNF is capable of exerting neuroprotective effects. In acute phases of injury, several reports indicate that both, BDNF alone [126, 127] or in any combination [128, 129] has improved functional recovery, neuronal survival, and tissue preservation. Moreover, BDNF has potent antioxidant effects and may be involved in regulation of immune responses after an SCI [130]. BDNF after SCI requires careful selection

TGF-β is a pleiotropic molecule with specific key functions in cell differentiation, proliferation, migration, immunosuppression, and extracellular matrix metabolism [131]. TGF-β could also be contributing to neuroprotective mechanisms

**Therapy Neuroprotective effects Ref.**

Improve functional recovery and reduce neuronal apoptosis, microglia activation, reduce pro-inflammatory cytokines like TNFα, IL-1β, and IL-6. Improve locomotor and sensory function and increase mRNA expression

Reduce cystic cavities size and suppress glial scar formation.

Induce modulation of inflammatory cytokines and oxidative stress. Increase functional recovery and reduce activation of glial fibrillary acidic

Reduce apoptosis and increase locomotor recovery. [151]

BMSCs + SCs Reduce the formation of the glial scar, remyelinate the injured axons, and

protein and increase myelination 4 weeks following SCI.

OECs Reduce cavity size, increase the neurofilaments sprouting and serotonin

SCs Upregulate the expression of NOS, activate the NO-dependent cyclic-GMP

Stimulate the expression of neural growth factor and BDNF.

myelination, reduce neuronal loss, and improve functional recovery.

OECs + SCs Diminish astrocyte number, microglia/macrophage infiltration and

pathway, which enhances neuronal survival.

Reduce inflammatory cytokines and ROS.

SCs + NSCs Promote neuronal differentiation, increase axonal regeneration/

[141–144]

[145–148]

[149]

[150]

[152]

[153]

[154, 155]

[156]

to consider the location, mode, and time of application after an injury.

Reduction in neutrophils and M1 macrophages. Downregulation of TNFα, IL-1 β, IL-6, and IL-12.

*DOI: http://dx.doi.org/10.5772/intechopen.89539*

*4.2.1 Brain-derived neurotrophic factor*

*4.2.2 Transforming growth factor-β*

NSCs Increase functional recovery.

of BDNF.

BMSCs Improve locomotor function and tissue protection. Increase the neurotrophic growth factor. Stimulate M2 macrophage activation.

promote functional recovery

axons, and improve functionality.

expression of CCL2 and CCL3.

**4.2 Growth factors**

*Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art DOI: http://dx.doi.org/10.5772/intechopen.89539*
