Trophic factors in patients with spinal cord injury

Introduction

Spinal cord injury (SCI) causes temporary or permanent changes in the motor, sensory, and autonomic functions of the spinal cord.

The main symptoms of SCI vary according to where the spinal cord damage occurred. Cervical injuries produce partial or total tetraplegia, shown by paralysis of the four extremities, while injuries in the lower areas induce paraplegia, in which paralysis of the lower body occurs and, in both cases urogenital and digestive alterations.

SCI can directly induce the death of different cell types such as neurons, oligodendrocytes, and astrocytes. Once damage has been generated in the spinal cord, secondary alterations such as demyelination of axons and apoptosis processes in oligodendrocytes occur (see review, ) ( Fig. 1 ).

Thus, in this chapter, we will review the main trophic factors that are released spontaneously in patients when SCI occurs. Likewise, to those trophic factors that are secreted when patients undergo rehabilitation and finally, the perspectives of its use in clinical trials after SCI.

Currently, the concept of trophic factor is applied to substances of a known or unknown nature that have specific effects on cells or tissues through specific receptors called Trk and p75. Particularly when the trophic factor act, on neurons and glia, they are called neurotrophic factors and its actions include support the growth, survival, neurotransmitters release, and differentiation in different stages of development, in maturity or in regenerative processes.

Although there is evidence of spontaneous recovery, they will largely depend on the magnitude of the injury, spinal level, age of the injury, patient’s condition, among others. However, spontaneous repair processes are initiated simultaneously in motor, sensory, and autonomous functions. Thus, the ability of intact corticospinal axons to sprout after SCI could present, as well as remyelination of injured axons.

Another approach to restoring the SCI and perhaps the most common strategy is rehabilitation and that produces environmental conditions that favor neurological recovery. Physical rehabilitation (exercise), electrical stimulation both directly to the muscle and to the spinal cord, produces motor and sensory improvements after SCI.

Cell therapies are used in order to create a suitable environment for restoration after SCI. The therapies include transplantation of stem cells, glial cells, and cells of the olfactory nervous system.

The treatment with trophic factor has been shown to improve conditions in different experimental animal models of SCI. The potential use of trophic factors in patients with SCI is evident, considering the possibility of improving the quality of life. However, a large number of clinical trials for its pharmacological use have to be carried out.

Role of neurotrophic factors in human neural plasticity after SCI

Spontaneous functional recovery in patients with spinal cord injury is limited, it occurs especially in patients in whom at least part of the sensory and motor functions has been preserved. This functional recovery stabilizes between 12 and 18 months and is mainly due to the conservation and sprouting of axons within the conserved medullary tissue adjacent to the injury site ( ). After SCI, plasticity processes involving axonal regeneration can occur, this reconnection of axons involves the regrowth of transected axons through a site of injury toward their original synaptic targets, while other forms of axonal sprouting result in the reorganization of the circuit; all these processes can lead to restoration of function ( ). However, many of the axonal sprouts are usually not beneficial, and even cause adverse functional effects such as neuropathic pain, spasticity, and dysreflexia ( ).

Neurotrophic factors can play an important role in structural and functional recovery after spinal cord injury and they are up or down regulation after the damage. These molecules are involved in axonal growth, remyelination, and modulation of the glial response after injury, among others ( ). This group of proteins is involved in the processes of natural plasticity after a spinal cord injury, which in patients has been described a relevant functional recovery without any type of treatment ( ). Not all neurons or spinal tracts express the same types of receptors, so they may preferentially be sensitive to a particular neurotrophic factor ( ). The importance of the main trophic factors involved in the intrinsic recovery of neural tissue after the spinal injury is described below.