Citation

Tadepalli SA, Kristóf Bali Z, Bruszt N, Nagy LV, Amrein K, Fazekas B, Büki A, Czeiter E, Hernádi I. Behav. Brain Res. 2019; ePub(ePub): ePub.

Affiliation

Department of Experimental Zoology and Neurobiology, Faculty of Sciences, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary; Translational Neuroscience Research Group, Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary; Center for Neuroscience, Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary; Grastyán Translational Research Centre, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary; Institute of Physiology, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs Hungary.

Copyright

(Copyright © 2019, Elsevier Publishing)

DOI

10.1016/j.bbr.2019.112268

PMID

31580914

Abstract

Repetitive mild traumatic brain injuries (TBI) impair cognitive abilities and increase risk of neurodegenerative disorders in humans. We developed two repetitive mild TBI models in rats with different time intervals between successive weight-drop injuries. Rats were subjected to repetitive Sham (no injury), single mild (mTBI), repetitive mild (rmTBI - 5 hits, 24 h apart), rapid repetitive mild (rapTBI - 5 hits, 5 min apart) or a single severe (sTBI) TBI. Cognitive performance was assessed 2 and 8 weeks after TBI in the novel object recognition test (NOR), and 6-7 weeks after TBI in the water maze (MWM). Acute immunohistochemical markers were evaluated 24 h after TBI, and blood biomarkers were measured with ELISA 8 weeks after TBI. In the NOR, both rmTBI and rapTBI showed poor performance at 2 weeks post-injury. At 8 weeks post-injury, the rmTBI group still performed worse than the Sham and mTBI groups, while the rapTBI group recovered. In the MWM, the rapTBI group performed worse than the Sham and mTBI groups. Acute APP and RMO-14 immunohistochemistry showed axonal injury at the pontomedullary junction in the sTBI, but not in other groups. ELISA showed increased serum GFAP levels 8 weeks after sTBI, while no differences were found between the injury groups in the levels of phosphorylated-tau and S100β.

RESULTS suggest that the rmTBI protocol is the most suitable model for testing cognitive impairment after mild repetitive head injuries and that the prolonged cognitive impairment after repetitive mild TBI originates from different structural and molecular mechanisms compared to similar impairments after single sTBI.

Copyright © 2019. Published by Elsevier B.V.

Language: en

Keywords

amyloid precursor protein; chronic traumatic encephalopathy; glial fibrillary acidic protein; memory; novel object recognition; water maze