1. Introduction

The spinal cord (SC) has three major functions in human beings: sensibility, autonomous control, and motor control. Destructive mechanisms following SCI can have grave consequences on these functions [1, 2].

Mechanical trauma initially tends to damage primarily gray central matter with a relative preservation of peripheral white matter. Irreversible damage to the gray matter occurs during the first hour after injury, with the same happening to white matter within the first 72 hours [5]. As a result of the mechanical injury, superficial vessels undergo vasospasm, originating an intraparenchymal hemorrhage, which damages the microvasculature of the gray matter [7]. This in turn leads to the decreased perfusion and local infarcts due to hypoxia and ischemia, depending on the severity of the lesion. Furthermore, these can be aggravated by neurogenic or hemorrhagic shock, arterial hypotension, bradycardia, arrhythmias, and intraparenchymal hemorrhage. Therefore, the damage initiated by mechanical trauma has a maximum extension from the third to fifth day after injury, extending from the rostral and caudal segments to the epicenter of the lesion, and affecting both gray and white matter. The main consequence of hemorrhage is neuronal death by necrosis, which is

Pharmacological and Nonpharmacological Therapeutic Strategies Based on the Pathophysiology of Acute…

http://dx.doi.org/10.5772/intechopen.72781

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The primary lesion causes the rupture of the blood brain barrier (BBB) at the injury site, leading to a focal destruction of neural tissue, which destabilizes neural and endothelial membranes [10]. This phenomenon results in the death of neurons in the hours following SCI, and is associated with edema, negatively impacting blood flow to the SC, thus extending the inflammatory response [11]. Therefore, primary injury gives rise to the cellular and molecular processes characteristic of the secondary injury stage, which promotes neuronal death and

Autodestructive mechanisms triggered after SCI can persist with time, and thus be found in acute, subacute, or chronic phases. The acute and subacute phases are characterized by the

The first secondary mechanism appearing after SCI, ionic deregulation results from an increase intracellular Na+ and Ca2+ concentration and a decrease of K+ and Mg2+ ions. This results in the depolarization of neuronal membranes, decreased number of ionic channels, and increased transportation of water molecules associated with Na+ and Ca2+ ions, leading to edema [13].

Vasogenic edema initially appears as a consequence of the BBB rupture, and is further propagated by the loss of ionic regulation, giving way to water accumulation in extracellular spaces. Water accumulation is strongly related to the intensity of the initial trauma [14]. The presence of edema in any part of the CNS results in the compression of adjacent tissue, which leads to ischemia and promotes the development of other self-destructive mechanisms, such as the

Once the lesion occurs, partial or total loss of the cellular membrane in neurons and axons is triggered, resulting in the depolarization due to the entrance of high concentrations of Ca2+ [13].

observed primarily in the gray matter [7–9].

alter genetic expression patterns [12].

release of FR, LP, and inflammation [1, 14].

2.1.3. Excessive release of intracellular calcium

following mechanisms:

2.1.1. Ionic deregulation

2.1.2. Edema

Traumatic SCI can originate devastating consequences on patients and those close to them, requiring a great number of lifestyle adjustments. This injury results most commonly from vehicular accidents, falls, and sports injuries, among other traumatic accidents. According to the World Health Organization (WHO), there are approximately between 250,000 and 500,000 cases of SCI per year. Among these, 90% are traumatic in nature with an increased mortality risk within the first year [3].

The pathophysiology of SCI can be divided into primary and secondary damage based on the self-destructive mechanisms following initial injury. These mechanisms can be further divided into three phases according to their temporality: acute, subacute, and chronic phase. The acute phase is characterized by ionic changes, which interrupt nerve impulses and lead to edema; the subacute phase involves a series of events including ischemia, vasospasm, thrombosis, inflammatory response, free radicals (FR) production, lipid peroxidation (LP), and the activation of autoimmune responses resulting in apoptosis. In the chronic phase, all the auto destructive mechanisms generated during the acute and subacute phase increase and demyelination processes are triggered, alongside the formation of a glial scar, which hinders axonal regeneration [4–6].

The objective of this chapter is to review a wide range of pharmacological and nonpharmacological therapeutic options, each targeting different pathological mechanisms in the different time phases of SCI.
