Caffeine: A Neuroprotectant and Neurotoxin in Traumatic Brain Injury (TBI)

Caffeine is a weak, nonselective adenosine receptor antagonist. At low-to-moderate doses, caffeine has a stimulating effect, however, at higher doses, it can act as a depressant. It can act both as a neuroprotectant and a neurotoxin. In experimental Traumatic Brain Injury (TBI), administration of this psychoactive drug has been associated with beneficial or detrimental effects, depending on the dose, model, and timing. In a healthy brain, it can boost alertness and promote wakefulness. On the other hand, its consumption during late adolescence and early adulthood disrupts normal pruning processes in the context of repetitive moderate TBI (mTBI), leading to changes in dendritic spine morphology resulting in neurological and behavioral impairments. Caffeine can potentially reduce TBI-associated intracranial pressure, oxidative stress, lipid peroxidation, cytotoxic edema, inflammation, and apoptosis. It can enhance alertness and reduce mental fatigue, which is critical for the cognitive rehabilitation of TBI patients. It has positive effects on immune cells and recovery post-TBI. It can improve cognitive function by antagonizing adenosine receptors involved in controlling synaptic transmission, synaptic plasticity, and synapse toxicity. On the contrary, studies have also reported caffeine consumers had significantly higher somatic discomfort compared to non-consumers. Therefore, we bring forth this review with the objective of exploring various studies and thoroughly examining the positive and negative role of caffeine in TBI.