Brain injury studies aim for new treatment targets

The National Institute of Environmental Health Sciences (NIEHS) has awarded a five-year, $1.5 million grant extension to Columbia University's Mailman School of Public Health to fund research into the function of a biomarker for brain injury called Translocator Protein 18 kDa, better known as TSPO, in order to better understand its function in brain injury and inflammation and discover targets for therapy.

Tomás Guilarte, PhD, chair of the Department of Environmental Health Sciences at Columbia University's Mailman School of Public Health, will lead the new studies. Dr. Guilarte pioneered these studies beginning in 1995 that led to the validation of the biomarker and established its use in research studies underway around the world.

When the brain is injured, TSPO levels increase markedly in the areas of brain injury. The process can be made visible using Positron Emission Tomography (PET), providing a real-time picture of where the damaging inflammation from injury is happening and the ability to track how treatment reduces this inflammation. But little is known about how or why this happens.

TSPO, previously known as Peripheral Benzodiazepine Receptor, plays a role in the production of steroids, which regulate inflammation. TSPO is present in the adrenal cortex and other peripheral organs that produce steroids; one of its best-known functions is the transport of cholesterol into mitochondria to produce pregnenolone, the parent compound for all steroids. But much remains to be known about the function of TSPO in the brain.

Dr. Guilarte will use cell culture systems and animal models to study the function of TSPO in microglia and astrocytes, the glia cells that express and increase TSPO at sites of brain injury. "By understanding the neurobiology of TSPO better, we believe we can open new avenues to treat inflammation and brain injury," he says. "There is evidence now that chemicals that bind to this protein have therapeutic potential."

The reference number for the continued NIEHS grant funding is #2 R01 ES007062. The NIEHS is part of the National Institutes of Health.

Provided by Columbia University's Mailman School of Public Health