2.1. Acute and subacute phases

Primary damage occurs mechanically at the moment of injury, leading to irreversible sequelae. There are three main mechanisms of injury:


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

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 alter genetic expression patterns [12].

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 following mechanisms:

### 2.1.1. Ionic deregulation

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].
