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In this study, healthy adult volunteers will undergo two positron emission tomography (PET) scans using the radiotracer [11C]PBR28 which binds to the 18kDa translocator protein (TSPO). Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral cytokine levels will be assayed periodically throughout the experimental session.
Specific aims: Quantify the magnitude of neuroimmune response after a classical immune stimulus.
Secondary aims: Quantify changes in cognitive function after a classical immune stimulus.
Hypothesis: Individuals will exhibit a robust whole-brain neuroimmune response and impaired cognitive function after LPS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LPS Challenge | Experimental | Subjects will undergo one 120-minute [11C]PBR28 PET scan before and one scan 3-hours after LPS administration (1.0ng/kg; IV). |
|
| LPS Follow-up | No Intervention | Subjects will undergo one 120-minute [11C]PBR28 PET scan 24+ hours after LPS. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lipopolysaccharide | Biological | Endotoxin E Coli |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Baseline TSPO Availability | Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions. | Before LPS administration (baseline) |
| Measure | Description | Time Frame |
|---|---|---|
| Alcohol Dependence Scale (ADS) - questionnaire | self-report questionnaire to determine severity of alcohol symptoms, 25 question multiple choice scale, range of 0-47 for a total score, with higher numbers indicating worse severity | baseline |
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Inclusion Criteria:
1) Medically-healthy male and female subjects able to read/write English
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kelly Cosgrove, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06519 | United States |
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| ID | Term |
|---|---|
| D008070 | Lipopolysaccharides |
| ID | Term |
|---|---|
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D011135 | Polysaccharides, Bacterial |
| D011134 | Polysaccharides |
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All subjects will complete one 120-minute [11C]PBR28 PET scan before and one scan 3-hours after lipopolysaccharide (LPS; 1.0ng/kg; IV) administration. A subset of subjects will complete a follow-up [11C]PBR28 PET scan 24+ hours after LPS.
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| D008055 |
| Lipids |
| D000942 | Antigens, Bacterial |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D004731 | Endotoxins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |