**7. Combined treatments**

As described in previous paragraphs, the use of different strategies as simple treatments in TSCI models promotes neuroprotection, axonal growth, and remyelination of damaged axons, and facilitates the improvement of locomotor function. Therefore, it has been determined that the combination of different strategies should be able to more effectively facilitate axonal growth and remyelination, helping to increase locomotor function.

The effect of using PPN transplantation in combination with ChABC or growth factors has been evaluated. It was shown that the animals with combined treatment had a greater number of regenerated axons and an increase in the improvement of locomotor function, unlike those animals with simple treatment [83, 84]. It was also demonstrated that by, in comparison with single treatments, combining PPN with FGFα, and PPN with ChABC, a favorable microenvironment was formed, increasing axonal growth [11, 85].

The effect of MSCs combined with chitosan bridges or with growth factors such as the granulocyte colony-stimulating factor (G-CSF) has also been studied, and it was observed that animals on combined treatments, compared to simple treatments, had greater axonal growth, thus improving locomotor function [46, 86]. In a chronic phase compression model, the combination of MSCs with ChABC increased axonal growth in comparison to single treatments [87].

It was also observed that animals, after 2 months of PPN and MSC transplants in a full-section model, had a greater number of growing axons by detecting GAP43 as well as an improvement in remyelination by detection of PBM and by electron microscopy, unlike animals treated with simple transplantation [88]. When making a triple combination of PPN with MSCs and ChABC, an increase in axonal regeneration was observed after 3 months, improving locomotor function [89].

On the other hand, the combination of ChABC with growth factors such as BDNF and NT-3 can promote greater axonal growth and favor the proliferation of oligodendrocytes, thus increasing remyelination compared to animals that only had separate treatments [71, 73, 74]. Also, in a full section model in the acute phase, the combination of ChABC with NT-3 increased axonal growth and improved locomotor function, unlike groups with single treatments [73]. It was also demonstrated in a chronic transection model that a ChABC injection with rehabilitation inhibited the formation of chondroitin sulfates, promoting increased axonal growth, unlike single treatment groups [72].

### **8. Clinical trials**

Independent of the type of traumatic spinal lesión (contusion, compression, or sectioning), the treatment of a spinal cord injury patient often begins at the site of the accident. Emergency personnel must gently and quickly immobilize and check the vital signs (urine retention, respiratory, and cardiovascular difficulty and formation



*Strategies to Repair Spinal Cord Injuries: Single Vs. Combined Treatments DOI: http://dx.doi.org/10.5772/intechopen.93392*

#### **Table 1.**

*Clinical trials of treatments for spinal cord injuries.*

of coagules in extremities) and prepare the patient for transport. In the clinic, doctors may apply anti-inflammatory drugs or lower the body temperature—a condition known as hypothermia—for 24–48 h to help prevent damaging inflammation. The patient is subjected to a careful medical inspection and examination, testing for sensory function and movement, and by asking some questions about the accident. In addition, X-rays, computerized tomography (CT) scanning, and/or magnetic resonance imaging (MRI) tests may be needed to reveal vertebral (spinal column) problems such as: tumors, fractures or degenerative changes in the spine, herniated disks, blood clots, or other masses that may be compressing the spinal cord. Often, a surgery intervention is necessary to remove fragments of bones, foreign objects, herniated disks, or fractured vertebrae that appear to be compressing the spine. Subsequently to these tests, doctors begin to analyze which treatment will be applied to the SCI patient.

Over the past few decades, several therapeutic strategies have been developed to target TSCI pathology in clinic, including single and combined treatments with the main objective to cover two important aspects: neuroprotection and neuroregeneration. **Table 1** summarizes several clinic trials used for the treatment of TSCI, which have advantages and disadvantages in their application. However, it needs to be mentioned that until now there are no effective treatments for TSCI, which promote complete regeneration and restoration of motor and systemic functions in humans. Since spinal cord injury research has relied on animal models to understand the mechanisms of disease and develop pre-clinical models of treatment, there is no successful translation from pre-clinical to patient interventions that could be attributed to the limited understanding of biological differences between human and animal model systems.
