Functional recovery following traumatic brain injury in rats is enhanced by bovine thymus nuclear extract supplementation

Traumatic brain injury (TBI) is one of the leading causes of death worldwide. Due to complex etiology, there are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long-lasting health consequences. One of the pathological manifestations of TBI is neuroinflammation, which is thought to delay tissue repair and patient recovery. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine glandular tissues, which can deliver a variety of nutrients and bioactive molecules. We show that bovine thymus-derived extracts contain antigens found in neural tissues and are relevant to neuroinflammation, and supplementation of rats with thymus extracts induces production of IgG antibodies against neuronal and glial antigens. In a rat model of controlled cortical impact (CCI) we determined that animals supplemented with a nuclear extract of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA-Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. Finally, we demonstrate that TNF supplement-induced increase in blood levels of IgG autoantibodies against nervous system antigens correlates with better animal performance on behavioral tests. Together, our data show, for the first time, that a nutritional supplement containing nuclear fraction of bovine thymus is potent at enhancing the functional recovery from TBI in a rat model, modulates signaling pathways implicated in TBI pathology and recovery at gene and protein levels, and may be beneficial for reducing neuroinflammation and improving tissue repair. Overall design: Expression profiling by RNA-Seq high throughput sequencing. 3 supplement treatments versus sham controls using adult male Sprague-Dawley (aged 6-7 weeks, from Charles River Laboratories).