Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis.

Area of Science:

• Neuroscience
• Immunology
• Radiology

Background:

• Human immunodeficiency virus (HIV)-associated neuroinflammation involves microglia and macrophage activation.
• Peripheral benzodiazepine receptor (PBR) is a marker for activated microglia and macrophages.
• Positron emission tomography (PET) offers a non-invasive method to measure PBR expression in the central nervous system (CNS).

Purpose of the Study:

• To evaluate the utility of PBR as a cellular activation marker in the CNS during HIV/SIV encephalitis.
• To measure PBR levels in the frontal cortex of SIV-infected macaques with encephalitis and compare them to uninfected controls.

Main Methods:

• Utilized PK11195 ligand autoradiography to measure PBR levels in the frontal cortex of SIV-infected and control macaques.
• Compared PK11195 binding with other microglial/macrophage activation markers (HAM56, KP-1) and astrocytic activation marker (GFAP) via quantitative image analysis.

Main Results:

• Significantly higher [(3)H]-(R)-PK11195 binding in both grey and white matter of SIV-encephalitic macaques compared to controls.
• Strong, significant association between PK11195 binding and HAM56/KP-1 immunostaining in white matter.
• No significant correlation between grey matter PK11195 binding and HAM56, KP-1, or GFAP immunostaining.

Conclusions:

• PBR, measured by PET, is a valid marker for microglia and macrophage activation in the CNS during SIV encephalitis.
• Functional neuroimaging in HIV-infected individuals should focus on subcortical white matter to assess microglia/macrophage activation.