Translocator Protein and Inflammation After Traumatic Brain Injury

Healthy, Traumatic Brain Injury (TBI)

Positron Emission Tomography (PET), Inflammation, Microglial Activation, Traumatic Brain Injury, TBI

Background: \- People with traumatic brain injury (TBI) often have inflammation in the brain. A protein called the translocator protein (TSPO) is often present with inflammation. Researchers want to see if a radioactive chemical known as \[11C\]PBR28 can be used to study TSPO and inflammation in the brain of people with TBI. Objectives: \- To test whether \[11C\]PBR28 can be used to study changes in the brain after a traumatic brain injury. Eligibility: * Individuals at least 18 years of age who have had TBI and have had a brain scan that shows signs of inflammation. * Healthy volunteers at least 18 years of age. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * All participants will have two brain scans during an outpatient visit. A magnetic resonance imaging scan will study brain activity. A positron emission tomography (PET) scan will use \[11C\]PBR28 to look for signs of TSPO and brain inflammation. * Participants with TBI will have two PET scans within 10 days of the head injury, and a PET scan around 90 days after the injury. They may also have MRI scans under this or another study. Tests of thinking, memory, and concentration will be used to study the effects of the injury and inflammation

Objective: Brain damage following traumatic injury (TBI) results from both direct (e.g., mechanical injury to the brain and vasculature) and indirect mechanisms (e.g., secondary mechanisms such as inflammation). While CT and MRI can help visualize the result of inflammatory processes in the brain for instance, the development of cerebral edema neither method can be used to document active inflammation itself. The translocator protein (TSPO), which is highly expressed in microglia and reactive astrocytes, has been used as a biomarker in positron emission tomography (PET) to identify active inflammatory processes. Recently, our laboratory developed PBR28, a new PET ligand that images TSPO with high levels of specific binding. We have successfully used PBR28 to investigate a number of brain disorders such as epilepsy, multiple sclerosis, and HIV infection with minor cognitive motor disorder, and are detecting neuroinflammation. The current protocol aims to explore whether PBR28 PET imaging can show changes in subjects with TBI who have shown MRI abnormalities in the acute phase and also in those who are in the chronic phase of TBI. Study population: The following three groups will be studied: TBI subjects who had brain injury within approximately 3 months and have exhibited MRI abnormalities consistent with TBI and who are enrolled in Evaluation, Pathogenesis, and Outcome of Subjects with or Suspected Traumatic Brain Injury (10-N-N122, PI Latour), Evaluation and Diagnosis of Potential Research Subjects with Traumatic Brain Injury (TBI), (11-N-0084, PI: Lawrence Latour), or other CNRM protocols. N = 20 TBI subjects who had brain injury more than approximately 5 month ago, are enrolled in 11-N-0084, and meet criteria of TBI established by CNRM. N = 20 Healthy age-matched volunteers. N = 20. Design: This is an exploratory study to determine whether PBR28 can detect the increased TSPO associated with neuroinflammation by scanning subjects who have shown MRI abnormalities in the acute phase. We also investigate whether PBR28 detects changes in the chronic phase as recently reported using an old ligand, PK 11195. Two groups of TBI subjects will be studied depending on their availability relative to the time of injury. To investigate changes in TSPO in the areas of MRI abnormalities in the acute phase, one group of TBI subjects (n = 20) will be studied who have shown TBI- related MRI abnormalities. These participants will have up to four PBR28 PET scans; one to two PET scans within approximately 10 days of head injury, a third PET scan approximately three months after injury, and a fourth scan approximately one year after the scan at \ three months. To study changes in TSPO in the chronic phase, another group of TBI subjects will be enrolled who had brain injury more than approximately 5 months but within 5 years ago and meet the criteria of TBI by CNRM. This separate group is included because some TBI subjects are being recruited by CNRM only sometime after the injury. The participants at the chronic phase will have one PET and one MRI scan. In addition to MRI data, for all TBI subjects, clinical information obtained in 10-N-N122 (only the acute phase) and 11-N-0084 (both acute and chronic phase) will be used to evaluate the utility of the PET data in order to better understand the pathology of TBI. Outcome Measures: In this exploratory study to investigate the ability of PBR28 PET to detect increases in TSPO, the primary goal will be to measure the magnitude and variance of any increases observed in PBR28 binding in areas of inflammation following TBI. Those data may be used to design future studies with a larger sample size.

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