Timothy J. Amrhein1, Talaignair N.
Venkatraman1, Haichen Wang2, Ines Batinic-Haberle3,
Christopher D. Lascola1
1Radiology, Duke University
Medical Center, Durham, NC, United States; 2Anesthesiology, Duke
University Medical Center, Durham, NC, United States; 3Radiation
Oncology, Duke University Medical Center, Durham, NC, United States
The paramagnetic superoxide dismutase mimetric MnTnHex-2-PyP5+ exhibits sufficient lipophilicity to allow for its accumulation within the brain despite an intact blood brain barrier. MR phantom experiments demonstrated their considerable T1 relaxation properties. Subsequently, a spreading depression rat model of microglial activity with an intact blood brain barrier demonstrated increased T1 relaxation within the experimental hemisphere after the administration of MnTnHex-2-PyP5+. This finding was successfully blocked via competitive inhibition with PK11195, a potent ligand of peripheral-type benzodiazepine receptors specific to activated microglia, suggesting a mechanism for localization and potential specificity for early brain injury states.