Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration

Lital Rachmany, David Tweedie*, Vardit Rubovitch, Yazhou Li, Harold W. Holloway, Dong Seok Kim, Whitney A. Ratliff, Jessica N. Saykally, Bruce A. Citron, Barry J. Hoffer, Nigel H. Greig, Chaim G. Pick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mild blast traumatic brain injury (B-TBI) induced lasting cognitive impairments in novel object recognition and less severe deficits in Y-maze behaviors. B-TBI significantly reduced the levels of synaptophysin (SYP) protein staining in cortical (CTX) and hippocampal (HIPP) tissues. Treatment with exendin-4 (Ex-4) delivered by subcutaneous micro-osmotic pumps 48 hours prior to or 2 hours immediately after B-TBI prevented the induction of both cognitive deficits and B-TBI induced changes in SYP staining. The effects of a series of biaxial stretch injuries (BSI) on a neuronal derived cell line, HT22 cells, were assessed in an in vitro model of TBI. Biaxial stretch damage induced shrunken neurites and cell death. Treatment of HT22 cultures with Ex-4 (25 to 100 nM), prior to injury, attenuated the cytotoxic effects of BSI and preserved neurite length similar to sham treated cells. These data imply that treatment with Ex-4 may represent a viable option for the management of secondary events triggered by blast-induced, mild traumatic brain injury that is commonly observed in militarized zones.

Original languageEnglish
Article number3735
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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