Persistent TBI symptoms linked to reduced growth hormone secretion, study reports

A team of researchers have discovered that persistent symptoms following TBI, such as sleep disturbance and memory problems, could be linked to reduced growth hormone production and demonstrate that hormone replacement therapy could alleviate symptoms.

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For many individuals who have sustained a traumatic brain injury, a series of health issues, such as depression, sleep disturbance and memory problems, can follow for years after their head injury.

At the University of Texas Medical Branch (TX, USA), a team of researchers have investigated this post-TBI syndrome over the past 20 years and have discovered that TBI results in a reduction in growth hormone (GH) secretion, which is why most TBI patients improve after GH replacement therapy.

The study, published in the Journal of Neuroscience, led to the definition of the syndrome as brain injury associated fatigue and altered cognition (BIAFAC). With the aim to develop new interventions the team have been trying to gain a better understanding of BIAFAC and why GH replacement therapy works so well.

"We already knew that even mild TBI triggers both short- and long-term changes to functional connections in the brain," commented team leader, Randall Urban (The University of Texas Medical Branch). "GH administration has been extensively linked with both protection and repair of the brain following damage or disease, however we didn't know much about the particular mechanisms and pathways involved."

A total of 18 participants with a history of TBI and inadequate GH secretion received GH replacement as part of a year-long, double-blind, placebo-controlled study. The researchers then assessed the participants for changes in physical performance, resting metabolic rate, fatigue and mood. Further, MRI techniques were utilized to observe changes in brain structure and functional connections.

As well as reducing fatigue, sleep disturbance, anxiety and depression, the team discovered that GH replacement treatment led to increased lean body mass and reduced fat mass. For the first time, the team were able to demonstrate that these changes are associated with better communication across brain networks previously linked with GH deficiency.  

"We noticed that TBI patients had altered amino acid and hormonal profiles suggesting chronic intestinal inflammation, so we recently completed a trial to investigate the role of the gut-brain axis in the long-lasting effects of TBI," explained Urban. "We compared the fecal microbes of 22 moderate/severe TBI patients residing in a long-term care facility with 18 healthy age-matched control subjects, identifying disruptions of intestinal metabolism and changes in nutrient utilization in TBI patients that could explain the reduced growth hormone function."

The findings from this comparison suggest that individuals with TBI-related fatigue and altered cognition have different fecal bacterial communities when compare with the control group. Therefore, supplementing or replacing dysbiotic intestinal communities may help to alleviate TBI symptoms.

"These two studies further characterize BIAFAC and act as a springboard for new treatment options," explained Urban. "We hope that the publications will focus the collective wisdom of the research community to better understand and treat this syndrome, providing hope for many. Because these symptoms can manifest months to years after the initial injury and as this cluster of symptoms hasn't been previously grouped together, it often goes unidentified in the medical community."

Source: The University of Texas Medical Branch. Traumatic brain injury impairs hormone production, disrupting sleep, cognition, memory. Press release: https://www.utmb.edu/

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