Epigenetic-immune-microbiota contribution to neural regeneration after spinal cord injury: an overview

Spinal cord injury (SCI) counts about 12,000 new cases each year in the United States. Since axons lose the competence to regenerate in adult mammals, SCI can lead to permanent neurological damages with dramatic personal, social and economic impacts. The long-term deficit of SCI results first from the type of insult and then from the secondary phase that includes many pathophysiological events. Among these, inflammation and epigenetic factors play a crucial role in the recovery of neuron connections. Indeed, variations in epigenetic and immune contribution can be associated to injury and, at systemic level, to age and health status as well as to microbiota profile of individuals at the time of, or consequent to SCI. Indeed, gut microorganisms, highly influence the immune system, but also produce bioactive substances such as folates, butyrate and acetate that participate to the epigenetic processes. Interestingly, variations in the profile of microbiota and bioactive substances have been described in patients with neurologic intestine because of SCI. Recently, advances in SCI regenerative medicine, such as stem cell therapy, biomaterial approach and laser therapy, have been obtained but they are still far from resolutive interventions. As the complexity of pathophysiological processes of the secondary phase can deeply condition the success of regeneration, here we provide a landscape of epigenetic-immune biomarkers of neurological recovery predisposition or prevention. We discuss most of data about epigenetics (microRNAs, circulating microRNAs and chromatin remodeling) after SCI in animal models. We also stress the microbiota epigenetic-immune modulation since controlling its composition and function is of therapeutic potential in regenerative medicine. Acknowledgements: Flagship InterOmics (PB05).