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

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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