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

Objectives: spinal cord injury (SCI) triggers a cascade of intrinsic pathophysiological events that influence the SCI long-term deficit and that should be therapeutically modulated. The aim is to identify biomarkers to favour neuronal recovery after SCI. Material and Methods: we reviewed the literature indexed in PubMed about SCI, SCI epigenetics, SCI microbiota and novel therapeutic strategies for SCI repair. Results: inflammation-epigenetics-microbiota vicious cycle affects recovery after SCI. The dysregulation of specific microRNAs and circulating microRNAs was found in spinal cord and in serum, respectively, after SCI thus circulating microRNAs are promising biomarkers for evaluating the severity of SCI, as demonstrated in animal models. SCI patients often display neurogenic intestine dysfunction including changes in gut microbiome composition with a significant reduction in butyrate producing bacteria. Butyrate is a potent anti-inflammatory agent, a histone deacetylase inhibitor and suppresses inflammation in the CNS probably reducing microglia-mediated neurotoxicity. In mice, induced gut dysbiosis exacerbates neurologic damage impairing recovery after SCI. To date, there is not a cure for SCI, however new regenerative approaches are recently suggested. In rats, valproic acid administration after SCI protects motoneurons through modulation of apoptotic pathways. The microRNA-based therapy, manipulating the expression of specific microRNAs can activate or block target genes involved in neuro-regeneration; advances in CNS microRNA delivery technologies able to cross the spinal cord blood barrier have been reached. In SC injured rats, passive cycling exercises modulated microRNAs and gene transcription favouring biochemical and cellular restore, and potentially damage recovery. Then again, regarding microbiota, probiotic-induced eubiosis improves loco-motor recovery in mice. New nutraceuticals have also been demonstrated to help in neuro-regeneration and SCI recovery. This is the case of Naringin, curcumin epigallocathechin-3-gallate, omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) that play anti-oxidant, anti-inflammatory and anti-apoptotic rules.