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.
Highlights
Traumatic brain injury (TBI) is a common ailment that presently lacks a first line pharmacological treatment approved by the US Food and Drug Administration (U.S FDA)
We investigate a clinically translatable dose of a neurotrophic and neuroprotective U.S FDA approved drug used for the treatment of type II diabetes mellitus, exendin-4 (Ex-4)- known as exenatide, in the setting of a mouse model of mild B-TBI14–16
Where behaviors and protein staining were altered by blast TBI (B-TBI) we observed that treatment with Ex-4, irrespective of the timing of treatment, attenuated the effects of the blast
Summary
Traumatic brain injury (TBI) is a common ailment that presently lacks a first line pharmacological treatment approved by the US Food and Drug Administration (U.S FDA). We found that a biaxial in vitro cell injury can induce abnormal neurite length and cell death that is amenable to attenuation by treatment with Ex-4. Taken together, these data suggest that treatment with the U.S FDA approved drug Ex-4 may possess clinically relevant benefits to patients who have experienced a mild blast traumatic brain injury, further studies are required to more fully explore the potential of Ex-4 as a treatment for human blast TBI
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