Current Research Projects

Brain-Periphery Crosstalk

Villapol's laboratory is interested in developing novel therapies for patients suffering from brain injury while performing exploratory research in the avenue of brain trauma and stroke. The central areas of investigation include the following topics:

The Role of Peripheral Inflammation and immune modulation on Brain recovery.

Traumatic Brain Injury (TBI) triggers a loss of brain tissue and, subsequently, a strong inflammatory response in the brain. In addition, TBI can alter the function of peripheral regions and other organs, eliciting systemic responses and global consequences. A focal injury to the brain elicits a rapid hepatic response, the production of chemokines by the liver acts as an amplifier of the focal injury response providing a route of CNS-liver communication. However, little is currently known regarding the inflammatory mediators and acute-phase proteins involved in the peripheral regions after brain injury, such as the liver. Furthermore, the extent of damage TBI inflicts on the peripheral organs remains largely unexplored. 

Microbiome and Neuropathology of traumatic brain injury and stroke

Gut microbiota are an essential neuromodulator of gut-brain axis signaling and can impact brain inflammation and outcome after ischemic injury. Several studies have shown that microbiota composition, diversity, and richness can influence anxiety- and depressive-like behaviors. Recently, we have focused on how TBI affects the function of peripheral systems, and in this project,  we are studying how TBI alters the microbiome and the resultant impact on TBI-induced affective disorders. We have previously shown that controlled cortical impact (CCI) in mice induces the development of distinctive depression, anxiety, and schizophrenia behaviors that are independent of injury severity, and our preliminary data will show that CCI causes a rapid shift in microbiota diversity within 24h of TBI, including a dramatic change in the diversity of the psychoactive Lactobacillus family. Based on our data, we are testing the hypothesis that changes to commensal gut microbiota after TBI modulates brain inflammation and drives the development of affective disorder phenotypes in mice.

Targeting serum amyloid A as a preventative measure for the onset of Alzheimer’s disease after head injury.

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The devastating deficiencies that result in the brain from traumatic brain injury (TBI) stem from multiple overlapping mechanisms, exacerbated by the fact that there are no effective treatments. TBI is recognized as the strongest environmental risk factor for neurodegenerative disease later in life, including dementia of Alzheimer's disease (AD)-type. Current TBI therapies have not lived up to expectations, investigating novel compounds that address multiple mechanisms is required to pursue neuroprotective efficacy. Serum Amyloid A1 (SAA1) is an acute phase protein involved in the chemotactic recruitment of inflammatory cells to the site of inflammation. After tissue damage, SAA1 is mainly produced in the liver and exported via peripheral circulation, directly affecting the pathogenesis of inflammation in other organs. We will use a well characterized animal model of TBI to determine the molecular association between SAA1 and Aβ deposition after TBI. This proposal will investigate whether in vivo gene SAA1 silencing improves clearance of soluble Aβ and reduces deposition into the injured brain.