Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy.

Traumatic brain injury (TBI) contributes to nearly a third of all injury-related deaths in the United States. For survivors of TBI, depending on severity, patients can be left with devastating neurological disabilities that include impaired cognition or memory, movement, sensation, or emotional function. Despite the efforts to identify novel therapeutics, the only strategy to combat TBI is risk reduction (helmets, seatbelts, removal of fall hazards, etc.

R-spondin1 deficiency enhances β-Cell neogenesis in a murine model of diabetes.

Objective: The cWnt activator, R-spondin1 (Rspo1), regulates β-cell growth, function, and neogenesis, although its role in conditions such as streptozotocin (STZ)-induced diabetes is unknown. We hypothesized that Rspo1 deficiency enhances β-cell neogenesis in STZ-induced diabetes.

Methods: Wild-type (Rspo1) and knockout (Rspo1) mice were injected with STZ (40 mg/kg) for 5 days, followed by analysis of oral glucose and insulin tolerance, and were killed on day 6 (acute; 9-11 mice) or 32 (chronic; 11-16 mice).

R-spondin-1 is a novel beta-cell growth factor and insulin secretagogue.

R-spondin-1 (Rspo1) is an intestinal growth factor known to exert its effects through activation of the canonical Wnt (cWnt) signaling pathway and subsequent expression of cWnt target genes. We have detected Rspo1 mRNA in murine islets and the murine MIN6 and betaTC beta-cell lines, and Rspo1 protein in MIN6 beta-cells. Rspo1 activated cWnt signaling in MIN6 beta-cells by increasing nuclear beta-catenin and c-myc, a cWnt target gene.