The potential roles of dopamine in traumatic brain injury: a preclinical and clinical update.

Traumatic brain injury (TBI) is one of the leading causes of death and disability, particularly among the young and the elderly. Several therapeutic options have been investigated, including drug interventions or combinational therapies. Although many drugs have shown promising results in the preclinical stage, all have failed in large clinical trials. Targeting the dopamine system is a novel TBI approach that provides benefits to functional outcomes. TBI could damage the dopaminergic system. Alterations in dopamine levels can impact cellular dysfunction and central nervous system (CNS) inflammation. Experimental evidence suggests that dopamine should be considered a first-line treatment to protect cerebral autoregulation and promote cerebral outcomes in TBI. Furthermore, investigation of dopamine-related genetic factors in relation to injury severity could also be of great significance for promoting TBI treatment. Importantly, various clinical lines of evidence have indicated that many dopamine agonists are beneficial when administered following injury in TBI patients. However, side effects of dopamine treatment prevent their use in TBI treatment, and there is a need for ongoing large, prospective, double-blind randomized controlled trials (RCTs) with these medications by the use of standardized criteria and outcomes to fully understand their effectiveness in this patient group. Here, we review the roles of dopamine in TBI and discuss the role that dopaminergic therapies have in neuroprotective strategies.