19.4 Neurorecovery

19.4.1 TBI Pathophysiology

Traumatic brain injury causes catastrophic damage at the cellular level from irreversible axonal divisioning and cell death, to massive extracellular release of glutamate and other excitotoxic molecules (Jain, 2008). Immediately following trauma a dramatic depolarization occurs, likely involving amino acids, causing ionic influx to cells. This process causes neuronal cell dysfunction and even death (Jain, 2008). Additionally, astrocyte swelling causes immediate and prolonged cerebral oedema and a rise in intracranial pressure (Jayakumar et al., 2008). Following the immediate trauma, two important processes contribute to continued brain damage. First, axonal damage occurs from axoplasmic transport impairment, not strictly from tissue shearing. Structural damage from the original insult appears not to be the primary explanation for axonal transport impairment rather it results from cytoskeletal collapse (Buki, & Povlishock, 2006). Second, the brain is hypersensitive to secondary ischemia from the release of many neurotransmitters (Jain, 2008). Other processes occurring post-TBI involve blood-brain barrier damage. Synthesis and release of nitric oxide increases blood-brain barrier permeability allowing post trauma molecules such as reactive oxygen species and inflammatory cytokines to influx (Jain, 2008). The increased permeability eventually causes barrier breakdown and contributes to cerebral oedema. Given the multidimensional nature of the brain trauma process, several acute care therapies have been devised to combat secondary insults. However, following the acute care period an understanding of brain plasticity is beneficial for developing strategies for the rehabilitation process.

19.4.2 Plasticity and Reorganization

When comparing human brains to animals’ of similar size (e.g., macaque, cat, etc.), scientist have found that, with the exception of the visual cortex, the number of neurons per unit area was comparable. The main difference between the structures is the total cortical surface area, of which humans have thicker cortex (Turkstra, & Holland, 2003). Researchers have demonstrated that this thickness is related to the extensive and widespread dendritic branches (Rockel et al.,1980). Brain capacity, and complexity, is guided by not only the number of neurons present in the brain but also by the number of connections between neurons, and human brains are characterized by a greater number of synpatic connections among cortical neurons. This important detail has implications for learning and recovery post injury. Recovery of the brain after injury is dependent on both the ability to regenerate or modify existing connections between neurons and develop new ones. This ability is best exemplified by the aging brain. As neurons are lost over time, the brain compensates by creating new connections so that the function of the dead neuron is not lost completely (Kolb, 1995). While the plasticity of the adult brain is not capable of complete reorganization, as is possible in the developing brain, significant changes are still conceivable. Thus, brain plasticity and reorganization have important implications for neurorehabilitation.

At present, there is no one pharmacological agent capable of fully restoring cognitive and motor-sensory function post-TBI. Emerging therapies have been designed to help to restore the brain’s internal milieu so that it can recover on its own. Brain injury recovery is unique, dynamic and multifactorial; the extent of neuronal loss is dependent upon the severity of injury and the cellular stress imposed by oedema and inflammation (Wieloch, & Nikolich, 2006). Recovery involves three interrelated processes: (1) activation of cell repair; (2) neuronal pathway modification; and (3) formation of new neuronal connections (Wieloch, & Nikolich, 2006). At the cellular level, changes in morphology occur including axonal growth, spine remodelling and spine activation. The ability of the brain to accomplish these processes depends on both promotion from the internal milieu and stimulation from the external environment in which the individual is located.  The timing of recovery and location of the recovery processes are variable within and between animals. Interestingly, some motor functions can and do recover within just a few days of the trauma. This suggests that silent pathways exist, or that certain synapses are unmasked or activated in times of need (Metz et al., 2005). Current research in experimental TBI has offered important insights into the neurorecovery process after brain injury. An understanding of brain plasticity and reorganization mechanisms is important for rehabilitation strategies.