**1. Introduction**

Supraspinal circuits related to motor function have a complex neuronal organization which physiological function is highly conserved in most of the vertebrate species. Those have an important role in the neural control of locomotion and other complex motor tasks [1]. Enormous effort has been made to discover a therapeutic strategy aiming descending pathways to recover movement after SCI, but there are still no effective results promoting recovery [2]. The loss of specific descending tracts is related to the levels of motor dysfunction after SCI. For example, the corticospinal tract is an important pathway for achieving fine adjustments during locomotion, thus, restoring its connectivity may partially contribute to recover some locomotor functions after injury [3]. Additionally, several studies have described the role of the red nucleus and rubrospinal tracts in the activation of the flexor phase within the gait locomotion [4, 5]. The reticulospinal neurons of the pons and the medulla activating the flexor phase during stepping provide position information related to the motor response. The reticular formation provides control of the posture during locomotors tasks [6].

Seminal studies made by Russian researchers in the last century described a region in the cat within the mesencephalon (midbrain) which was named as mesencephalic locomotor region (MLR) [7]. They concluded that electrical stimulation to the MLR elicits coordinated locomotion. This circuit accesses descending spinal neurons from the reticular formation to transmit locomotion signals [8]. Today, this region is considered a target for electrical stimulation following a SCI because there is proof that homologous areas in the brainstem of humans can be identified as a MLR with some differences due to the possible adaptation to bipedalism [9].

It has been well documented that the above mentioned supraspinal circuits can contribute to remodel the spinal cord and promote in some extent, recovery after incomplete SCI [10]. The neural circuits within the spinal cord can exhibit a degree of plasticity at cellular level [11], therefore, these newly connections would allow the formation of new pathways that may contribute to functional sensorimotor recovery.

Although the neurologic classification of the AIS-ASIA (The American Spinal Injury Association Impairment Scale) as A represents total motor and sensory loss below the injury level, a complete section of the spinal cord is not frequently observed in the clinic. In a postmortem study, it was found that around 75% of subjects diagnosed with complete SCI, some portions of the spinal cord in the site of injury were preserved, representing "continuity" across tissue [12]. In 1998, Dimitrijevic and colleagues [13] described that some subjects AIS-ASIA A were able to produce voluntary motor activation in some muscles during epidural stimulation. It was evident that some spared fibers across injury were still functional, suggesting the term "discomplete" to describe this observation. This concept opened new questions regarding potential rehabilitation strategies developed in animal models. Unfortunately, translation into the clinic has not succeeded so far. Anatomical and physiological aspects are among the differences between animal models and humans [14]. However, in the last decade, new approaches have shown promising results in subjects with complete and incomplete SCI.

#### **1.1 Neuroplasticity**

Afferent inputs integrate sensory information that modulates the process of movement and theproprioception phenomena, cutaneous stimulation promotes the increase of spinal cord excitability and promotes plastic changes within the locomotor apparatus in humans [15]. Proprioceptive feedback contributes substantially

#### *The Role of Supraspinal Structures for Recovery after SCI: From Motor Dysfunction to Mental… DOI: http://dx.doi.org/10.5772/intechopen.96140*

to the posture maintenance phase of extensor activity as described in cats during treadmill locomotion [16, 17] and in humans [18], as well as improving motor functions with physical exercises designed to stimulate cortical and subcortical neural circuits [19] When SCI occurs, the supraspinal elements such as the corticospinal tracts often decreases its connectivity to its direct or indirect targets (i.e. lumbar CPGs); interestingly, the terminal territory of the motor cortex do not change significantly as compared to the somatosensory cortex, while the afferents fibers exhibit aberrant connections into deafferented regions of the spinal cord as described in monkeys [20]. In addition, proprioceptive neurons are relevant in the process of recovery within SCI, for example, it has been suggested that the neurons receiving feedback signals can help to reorganize motor circuits [21, 22].

The process for mediating remodeling of supraspinal circuits requires the specific selection for synaptic reconnection between supraspinal circuits and the deafferented spinal cord regions. Bradley et al. [23] proved that cyclic AMP response element-binding protein and NMDA receptors have a significant role in the process of reconnection since those promote the and reinforce the connections of relay neurons to the spinal cord in the mouse.

As mentioned above, many supraspinal circuits contribute to activate locomotor tasks. Strategies involving a combination of clinical treatments have been developed with the aim to predict restoration based on early clinical symptoms. Most of these methods correlated variables that indirectly influence supraspinal centers in the production of walking in humans [24].

After an SCI, the reaction of the glial tissue ends in the formation of a scar. There is great therapeutic potential in the ability to modulate the healing of glial cells in response to damage in the CNS. *In vivo* and *in vitro* studies, although relatively limited, have shown improvement in axonal regeneration and functional recovery after specific constituent's inhibition of the glial scar. Enzymatic digestion of GAG's (Glycosaminoglycans) chains of CSPGs (chondroitin sulfate and keratane proteoglycans), for example, stimulates axonal regeneration at the site of damage or injury [25, 26]. Axons chronically damaged in the SC can regenerate through implants of peripheral nerve grafts after 4 weeks of injury [27]. Even in lesions of one year of progression, regeneration of the rubrospinal tracts in adult animals has been described. This can be achieved with cells that are treated with the application of BDNF, allowing the normal conditions of the soma to be restored [28]. In the last decade, combined treatments with Chondroitinase ABC, or with novel forms to release and integrate this enzyme in the tissue has also been developing to improve plasticity and reconnection of the cells found at the injury site [29–32]. Therefore, biochemical and pharmacological management is important to reduce the glial scar and facilitate axonal regeneration and neuronal reconnection.
