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 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.

HypothesisFor 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

Blast Injury

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

Timeline

Behavioral Testing

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

(BM)

Open Field

Anxiety: EPM

Spatial Learning & Memory: BM

Immunohistochemistry

GFAP: CNS glia – Green

Caspase 3: Cell apoptosis – Red

DAPI: Cell nuclei – Blue

Ventral HippocampusGFAP/Cas3, 10x

a. Control Minocycline b. Control bTBc. bTBI Minocycline

a

b

c

Ventral HippocampusGFAP/Cas3, 60x

a. Control Minocycline b. Control bTBc. bTBI Minocycline

a

b

c

Dorsal HippocampusGFAP/Cas3, 10x

a. Control Minocycline

b. Control bTBc. bTBI Minocycline

a

b

c

Dorsal HippocampusGFAP/Cas3, 60x

a. Control Minocycline

b. Control bTBc. bTBI Minocycline

a

b

c

Conclusions

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

The TeamKasper Lab

Dr. Andrei BlohkinMAJ Antoinnette ShinnCDR Stephanie BardackCol Susan PerryMohammad Elsayed

Dr. Neil Grunberg

VA Merit Award B5044R

Dr. Denes Agoston Dr. Erzsebet KovesdiAlaa KamnakshDr. Farid AhmedDaniel Wingo

Dr. Joseph Long, WRAIR