Brain trauma and the secondary cascade in humans: review of the potential role of vitamins in reparative processes and functional outcome

An estimated sixty-nine million people sustain a traumatic brain injury each year. Trauma to the brain causes the primary insult and initiates a secondary biochemical cascade as part of the immune and reparative response to injury. The secondary cascade, although a normal physiological response, may also contribute to ongoing neuroinflammation, oxidative stress and axonal injury, continuing in some cases years after the initial insult. In this review, we explain some of the biochemical mechanisms of the secondary cascade and their potential deleterious effects on healthy neurons including secondary cell death. The second part of the review focuses on the role of micronutrients to neural mechanisms and their potential reparative effects with regards to the secondary cascade after brain injury. The biochemical response to injury, hypermetabolism and excessive renal clearance of nutrients after injury increases the demand for most vitamins. Currently, most research in the area has shown positive outcomes of vitamin supplementation after brain injury, although predominantly in animal (murine) models. There is a pressing need for more research in this area with human participants because vitamin supplementation post-trauma is a potential cost-effective adjunct to other clinical and therapeutic treatments. Importantly, traumatic brain injury should be considered a lifelong process and better evaluated across the lifespan of individuals who experience brain injury.