The genetic basis of inter-individual variation in recovery from traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of death among young people, and is increasingly prevalent in the aging population. Survivors of TBI face a spectrum of outcomes from short-term non-incapacitating injuries to long-lasting serious and deteriorating sequelae. TBI is a highly complex condition to treat; many variables can account for the observed heterogeneity in patient outcome. The limited success of neuroprotection strategies in the clinic has led to a new emphasis on neurorestorative approaches. In TBI, it is well recognized clinically that patients with similar lesions, age, and health status often display differences in recovery of function after injury. Despite this heterogeneity of outcomes in TBI, restorative treatment has remained generic. There is now a new emphasis on developing a personalized medicine approach in TBI, and this will require an improved understanding of how genetics impacts on long-term outcomes. Studies in animal model systems indicate clearly that the genetic background plays a role in determining the extent of recovery following an insult. A candidate gene approach in human studies has led to the identification of factors that can influence recovery. Here we review studies of the genetic basis for individual differences in functional recovery in the CNS in animals and man. The application of in vitro modeling with human cells and organoid cultures, along with whole-organism studies, will help to identify genes and networks that account for individual variation in recovery from brain injury, and will point the way towards the development of new therapeutic approaches.