Dennis Simon, MD Awarded R21 Grant to Study Microbiome-mediated Neuroprotection in TBI

Assistant professor of Critical Care Medicine, Dennis Simon, MD was awarded an R21 grant entitled, “Gut Microbial Metabolite-mediated Neuroprotection in Traumatic Brain Injury” from the National Institute of Neurological Disorders and Stroke. The multi-PI grant includes Bob Clark, MD, professor of Critical Care Medicine and Pediatrics and vice chair for Pediatric Critical Care in the Department of Critical Care Medicine, and Michael Morowitz, MD, associate professor of Surgery in the Division of Pediatric Surgery, Department of Surgery at the University of Pittsburgh.

“Millions of Americans are living with persistent neuroinflammation and neurodegenerative disorders related to a previous TBI, sometimes years after their primary injury,” said Dr. Simon.

The study seeks to discover if persistent inflammation-mediated neurodegeneration after TBI is fueled by depletion of commensal bacteria and deficient microbial production of the short chain fatty acid acetate. The investigators propose that chronic intestinal dysbiosis, specifically the depletion of healthy commensal bacteria capable of fermenting dietary fiber to produce acetate, leads to a stable maladaptive state in the brain, chronic inflammation, and neurodegeneration after TBI.

They will collaborate with scientists at three internationally-recognized centers for TBI and microbiome research—The Safar Center for Resuscitation Research, the Center for Microbiome and Medicine, and the Brain Care Institute at the University of Pittsburgh—to address three specific aims:

  • Determine whether acetate repletion using a chow enriched with acetylated fiber or replenishing acetate-producing bacteria in the gut prevents late neurodegeneration after TBI,
  • Determine the impact of acetate repletion on chronic microglial activation after TBI by immunohistochemistry and use RNA-Seq to determine microglia phenotype,
  • Characterize temporal changes in serum and fecal acetate levels in children admitted to the intensive care unit with TBI.

Dr. Simon is a pediatric intensivist at UPMC Children’s Hospital of Pittsburgh, where he is also the director for Pediatric Neurocritical Care and the program director for the Pediatric Neurocritical Care Fellowship. He holds a BS in Biology and Biochemistry from Duke University, and MD from SUNY Stony Brook. He undertook his residency in Pediatrics at the Boston Combined Program followed by a move to Pittsburgh for his Fellowship in Pediatric Critical Care Medicine at UPMC Children’s Hospital of Pittsburgh.