Traumatic brain injury (TBI) is one of the world’s leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca²⁺. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the damaging impact and this damage is irreversible. Secondary mechanisms, which begin as early as a few minutes after the initial trauma, include processes such as spinal cord ischemia, cellular excitotoxicity, ionic dysregulation, and free radical-mediated peroxidation. SCI is featured by different forms of injury, investigating the pathology and degree of clinical diagnosis and treatment strategies, the animal models that have allowed us to better understand this entity and, finally, the role of new diagnostic and prognostic tools such as miRNA could improve our ability to manage this pathological entity. Autopsy could benefit from improvements in miRNA research: the specificity and sensitivity of miRNAs could help physicians in determining the cause of death, besides the time of death.

The acronym TBI refers to traumatic brain injury, an alteration of brain function, or an evidence of brain pathology, that is caused by an external force. TBI is estimated to become the third leading cause of permanent disability and mortality worldwide. TBI-related injuries can be classified in many ways, according to the degree of severity or the pathophysiology of brain injury (primary and secondary damage). Numerous cellular pathways act in secondary brain damage: excitotoxicity (mediated by excitatory neurotransmitters), free radical generation (due to mitochondrial impairment), neuroinflammatory response (due to central nervous system and immunoactivation) and apoptosis. In this scenario, microRNAs are implicated in the regulation of almost all genes at the post-transcriptional level. Several microRNAs have been demonstrated to be specifically expressed in particular cerebral areas; moreover, physiological changes in microRNA expression during normal cerebral development upon the establishment of neural networks have been characterized. More importantly, microRNAs show profound alteration in expression in response to brain pathological states, both traumatic or not. This review summarizes the most important molecular networks involved in TBI and examines the most recent and important findings on TBI-related microRNAs, both in animal and clinical studies. The importance of microRNA research holds promise to find biomarkers able to unearth primary and secondary molecular patterns altered upon TBI, to ultimately identify key points of regulation, as a valuable support in forensic pathology and potential therapeutic targets for clinical treatment.