Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI

Specific ablation of the NCoR corepressor δ splice variant reveals alternative RNA splicing as a key regulator of hepatic metabolism.

The NCoR corepressor plays critical roles in mediating transcriptional repression by both nuclear receptors and non-receptor transcription factors. Alternative mRNA splicing of NCoR produces a series of variants with differing molecular and biological properties. The NCoRω splice-variant inhibits adipogenesis whereas the NCoRδ splice-variant promotes it, and mice bearing a splice-specific knockout of NCoRω display enhanced hepatic steatosis and overall weight gain on a high fat diet as well as a greatly increased resistance to diet-induced glucose intolerance. We report here that the reciprocal NCoRδ splice-specific knock-out mice display the contrary phenotypes of reduced hepatic steatosis and reduced weight gain relative to the NCoRω-/- mice. The NCoRδ-/- mice also fail to demonstrate the strong resistance to diet-induced glucose intolerance exhibited by the NCoRω-/- animals. The NCoR δ and ω variants possess both unique and shared transcriptional targets, with expression of certain hepatic genes affected in opposite directions in the two mutants, others altered in one but not the other genotype, and yet others changed in parallel in both NCoRδ-/- and NCoRω-/- animals versus WT. Gene set expression analysis (GSEA) identified a series of lipid, carbohydrate, and amino acid metabolic pathways that are likely to contribute to their distinct steatosis and glucose tolerance phenotypes. We conclude that alternative-splicing of the NCoR corepressor plays a key role in the regulation of hepatic energy storage and utilization, with the NCoRδ and NCoRω variants exerting both opposing and shared functions in many aspects of this phenomenon and in the organism as a whole