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Christine E. Kasper, PhD, RN, FAAN Dept. of Veterans Affairs &

Neurobehavioral Impairment is Prevented by Acute Minocycline Treatment in a Rodent Model of mild Blast Traumatic Brain Injury. Christine E. Kasper, PhD, RN, FAAN Dept. of Veterans Affairs & Professor, USUHS Graduate School of Nursing. Aim.

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Christine E. Kasper, PhD, RN, FAAN Dept. of Veterans Affairs &

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  1. Neurobehavioral Impairment is Prevented by Acute Minocycline Treatment in a Rodent Model of mild Blast Traumatic Brain Injury Christine E. Kasper, PhD, RN, FAAN Dept. of Veterans Affairs & Professor, USUHS Graduate School of Nursing

  2. Aim To determine the effect of acute treatment with minocycline, an FDA approved non-steroidal anti-inflammatory drug, on the functional and molecular outcomes of mild blast TBI.

  3. Hypothesis For dorsal and ventral hippocampus: Anti-inflammatory treatment with minocycline will improve the functional outcome in mbTBI Anti-inflammatory treatment with minocycline will decrease cell apoptosis and reduce neural inflammation

  4. Blast Injury

  5. Method • 245-265 g male Sprague Dawley Rats • N = 32 • Normal housing (2/cage) • 4 Groups: • Sham saline treated N = 8 • Sham mincocycline treated N = 8 • Blast injured saline treated N = 8 • Blast injured minocycline treated N = 8

  6. Timeline

  7. Behavioral Testing • 8 and 45 days post-bTBI: • Locomotion: Open Field (OF) • Anxiety: Elevated Plus Maze (EPM) • Spatial Learning & Memory: Barnes Maze (BM)

  8. Open Field

  9. Anxiety: EPM

  10. Spatial Learning & Memory: BM

  11. Immunohistochemistry GFAP: CNS glia – Green Caspase 3: Cell apoptosis – Red DAPI: Cell nuclei – Blue

  12. Ventral HippocampusGFAP/Cas3, 10x a c b Control Minocycline Control bTB bTBI Minocycline

  13. Ventral HippocampusGFAP/Cas3, 60x c a b Control Minocycline Control bTB bTBI Minocycline

  14. DorsalHippocampusGFAP/Cas3, 10x a c b Control Minocycline Control bTB bTBI Minocycline

  15. DorsalHippocampusGFAP/Cas3, 60x c a b Control Minocycline Control bTB bTBI Minocycline

  16. Conclusions Minocycline is effective in reducing inflammation and apoptotic cell death in the dorsal and ventral hippocampus following mild blast TBI.

  17. The Team Dr. Denes Agoston Dr. ErzsebetKovesdi AlaaKamnaksh Dr. Farid Ahmed Daniel Wingo Dr. Joseph Long, WRAIR Kasper Lab Dr. Andrei Blohkin MAJ Antoinnette Shinn CDR Stephanie Bardack Col Susan Perry Mohammad Elsayed Dr. Neil Grunberg VA Merit Award B5044R

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