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

doi:10.1038/s41598-017-03792-9

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 journal › Article › peer-review

42 Scopus citations

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 language	English
Article number	3735
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-03792-9
State	Published - 1 Dec 2017

Access to Document

10.1038/s41598-017-03792-9

Cite this

Rachmany, L., Tweedie, D., Rubovitch, V., Li, Y., Holloway, H. W., Kim, D. S., Ratliff, W. A., Saykally, J. N., Citron, B. A., Hoffer, B. J., Greig, N. H., & Pick, C. G. (2017). Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration. Scientific Reports, 7(1), Article 3735. https://doi.org/10.1038/s41598-017-03792-9

@article{14d8312449524d36a1c1c5f2f724abd6,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41598-017-03792-9",

language = "אנגלית",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Rachmany, L, Tweedie, D, Rubovitch, V, Li, Y, Holloway, HW, Kim, DS, Ratliff, WA, Saykally, JN, Citron, BA, Hoffer, BJ, Greig, NH & Pick, CG 2017, 'Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration', Scientific Reports, vol. 7, no. 1, 3735. https://doi.org/10.1038/s41598-017-03792-9

TY - JOUR

T1 - Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration

AU - Rachmany, Lital

AU - Tweedie, David

AU - Rubovitch, Vardit

AU - Li, Yazhou

AU - Holloway, Harold W.

AU - Kim, Dong Seok

AU - Ratliff, Whitney A.

AU - Saykally, Jessica N.

AU - Citron, Bruce A.

AU - Hoffer, Barry J.

AU - Greig, Nigel H.

AU - Pick, Chaim G.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85020866196&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-03792-9

DO - 10.1038/s41598-017-03792-9

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:85020866196

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 3735

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this