Mild traumatic brain injury as a pathological process

Abstract

Traumatic brain injury (TBI) is defined as dysfunction or other evidence of brain pathology caused by external physical force. More than 69 million new cases of TBI are registered worldwide each year, 80% of them - mild TBI. Based on the physical mechanism of induced trauma, we can separate its pathophysiology into primary and secondary injuries. Many literature sources have confirmed that mechanically induced brain injury initiates ionic, metabolic, inflammatory, and neurovascular changes in the CNS, which can lead to acute, subacute, and chronic neurological consequences. Despite the global nature of the disease, its high heterogeneity, lack of a unified classification system, rapid fluctuation of epidemiological trends, and variability of long-term consequences significantly complicate research and the development of new therapeutic strategies. In this review paper, we systematize current knowledge of biomechanical and molecular mechanisms of mild TBI and provide general information on the classification and epidemiology of this complex disorder.

Keywords: Acute injury; Excitotoxicity; Glial reactivity; Mild traumatic brain injury; Post-traumatic neurodegeneration; Subacute injury.

Fig. 1

Progress of traumatic brain injury events. TBI leads to the overall cellular homeostasis of the brain. Damage of cell membranes causes further activation of microglia and astrocytes; release of intracellular calcium; production of chemokines and cytokines that activates of immune system. In addition, there are changes in the functioning of GLT-1 as a glutamate transporter, while excess glutamate causes excitotoxicity. Taken together, these factors contribute to changes in blood flow, deterioration of oxidative stress consequences, loss of neuronal survival, and in the long term, cognitive decline and neuroinflammation.