Battlefield blast exposure related to improvised
explosive devices (IEDs) has become the most common cause of
traumatic brain injury (TBI) in the recent conflicts in Iraq and Afghanistan. Mental health problems are common after TBI. A striking feature in the most recent veterans has been the frequency with which mild TBI (mTBI) and
posttraumatic stress disorder (
PTSD) have appeared together, in contrast to the classical situations in which the presence of mTBI has excluded the diagnosis of
PTSD. However, treatment of
PTSD-related symptoms that follow
blast injury has become a significant problem.
BCI-838 (
MGS0210) is a Group II
metabotropic glutamate receptor (
mGluR2/3) antagonist
prodrug, and its active metabolite BCI-632 (
MGS0039) has proneurogenic, procognitive, and
antidepressant activities in animal models. In humans,
BCI-838 is currently in clinical trials for
refractory depression and suicidality. The aim of the current study was to determine whether
BCI-838 could modify the anxiety response and reverse
PTSD-related behaviors in rats exposed to a series of low-level blast exposures designed to mimic a human mTBI or subclinical blast exposure.
BCI-838 treatment reversed
PTSD-related behavioral traits improving anxiety and fear-related behaviors as well as long-term recognition memory. Treatment with
BCI-838 also increased neurogenesis in the dentate gyrus (DG) of blast-exposed rats. The safety profile of
BCI-838 together with the therapeutic activities reported here, make
BCI-838 a promising
drug for the treatment of former battlefield Warfighters suffering from
PTSD-related symptoms following blast-induced mTBI.