Grace Niziolek, MD
Assistant Professor, WashU Surgery
- Phone: 314-362-5298
- Email: gracen@nospam.wustl.edu
Exploring the mechanisms of blood brain barrier dysfunction that lead to chronic neuroinflammation and neurodegeneration
Each year, nearly 3 million Americans are diagnosed with traumatic brain injuries (TBI). Though the majority of these patients will have mild injuries, 56,000 people will die each year as a result of their TBI. Increasingly, TBI is being described as a chronic health problem, as patients often experience a variety of physical ailments, psychiatric disorders, and diminished quality of life.2 Multiple pathophysiologic mechanisms are at play in acute and chronic TBI, including oxidative stress, apoptosis, coagulopathy, blood brain barrier dysfunction, systemic inflammation and local neuroinflammation. Despite the significant public health impact of TBI, there have been no clinically significant breakthroughs in TBI research for several decades.
As a new investigator, I am interested in exploring the mechanisms of blood brain barrier dysfunction that lead to chronic neuroinflammation and neurodegeneration. Specifically, I hope to determine the role of sphingosine-1-phosphate in glycocalyx shedding, blood brain barrier permeability, tight junction maintenance, systemic inflammation, and neuroinflammation following TBI. Given the wide and varied TBI phenotype, experiments are designed not only to evaluate changes at the molecular and cellular level, but also at the neurobehavioral level. In particular, murine experiments incorporate depression and anxiety testing as well as test to evaluate memory, spatial learning, and motor ability. The ultimate goal of any preclinical testing is direct translation into the hospital setting for those patients with moderate and severe TBIs.