Beyond Acute Traumatic Brain Injury: Molecular Implications of Associated Neuroinflammation in Higher-Order Cognitive Processes

AGUSTÍN J. MONTIVERO, ; MARISA S. GHERSI; JOHANNA CATALÁN-FIGUEROA; MARÍA LINA FORMICA; NAHUEL CAMACHO; ANTONELLA F. CULASSO; CLAUDIA B. HEREÑÚ; SANTIAGO D. PALMA; MARIELA FERNANDA PÉREZ

Psychiatry and Neuroscience Update

Springer,

Año: 2021; p. 237 - 259

Traumatic brain injury (TBI) is a worldwide major clinical problem affecting millions of individuals annually which report chronic disabilities long after the initial injury event. Besides the early mechanical damage, TBI can induce a process of secondary injury which can lead to long-term neurological and neuropsychiatric sequelae. Aside from the established risk for neurodegenerative disease, the most frequently reported behavioral, affective, or psychological changes concerned irritability, bad temper, tiredness, depression, rapid mood change, and anxiety. These changes can impact on higher-order cognitive processes. Secondary brain injury is caused mainly due to metabolic, synaptic, and vascular alterations, along with neuroinflammatory processes and oxidative stress. These events are associated to excitotoxicity that produces an ionic imbalance and cellular edema. Finally, the unfolded protein response is triggered, as well as the generation of toxic and pro-inflammatory mediators, which in turn may induce reticulum stress, apoptosis, and/or necrosis. No pharmacological therapy has proven to be useful against secondary injury. Current therapeutic strategies in the management of TBI are limited to decrease intracranial pressure and thus improving cerebral blood flow. In this chapter we reviewed the molecular mechanisms underlying secondary injury that can be explored as possible targets for development of new therapeutic agents to treat many of the long-term sequelae and provide life improvements for those suffering from TBI. In addition, the different micro-/nanotechnologies and devices that have been tested as strategies for drug delivery were discussed.