Neurobehavioral, cellular, and molecular consequences of single and multiple mild blast exposure

Abstract

Mild traumatic brain injury, caused by the exposure to single or repeated blast overpressure, is a principal concern due to its pathological complexity and neurobehavioral similarities with posttraumatic stress disorder. In this study, we exposed rats to a single or multiple (five total; administered on consecutive days) mild blasts, assessed their behavior at 1 and 16 days postinjury) and performed histological and protein analyses of brains and plasma at an early (2 h) and a late (22 days) termination time point. One day postinjury, multiple-injured (MI) rats showed the least general locomotion and the most depression- and anxiety-related behaviors among the experimental groups; there were no such differences at 16 days. However, at the later time point, both injured groups displayed elevated levels of select protein biomarkers. Histology showed significantly increased numbers of TUNEL+ (terminal-deoxy-transferase-mediated dUTP nick-end labeling)-positive cells in the dorsal and ventral hippocampus (DHC and VHC) of both injured groups as early as 2 h after injury. At 22 days, the increase was limited to the VHC of MI animals. Our findings suggest that the exposure to mild blast overpressure triggers early hippocampal cell death as well as neuronal, glial, and vascular damage that likely contribute to significant, albeit transient increases in depression- and anxiety-related behaviors. However, the severity of the observed pathological changes in MI rats failed to support the hypothesized cumulative effect of repeated injury. We infer that at this blast frequency, a potential conditioning phenomenon counteracts with and reduces the extent of subsequent damage in MI rats.

Lack of chronic neuroinflammation in the absence of focal hemorrhage in a rat model of low-energy blast-induced TBI

“…However, by day 22, an apparent increase in GFAP immunoreactivity was observed in the hippocampus of the multiple blast-exposed rats. In both the single and multiple blast-exposed groups, increased apoptosis was found in the hippocampal hilus [27] .…”

“…In the frontal cortex, hippocampus, and cerebellum, the expression of IL receptors was significantly reduced, whereas the expression of TNF-α and its receptors was increased [55]. In rats subjected to multiple 138-kPa blast exposures (5×), plasma levels of vascular endothelial growth factor (VEGF) and neuron-specific enolase (NSE) were significantly elevated after 2 h compared to levels in sham controls and rats exposed to a single blast [27]. By day 22 post-injury, animals exposed to either a single blast or multiple blasts had significantly higher levels of VEGF, neuron-specific enolase (NSE), neurofilament H (NFH), and GFAP than did those in the noninjured control groups [27].…”

“…In rats subjected to multiple 138-kPa blast exposures (5×), plasma levels of vascular endothelial growth factor (VEGF) and neuron-specific enolase (NSE) were significantly elevated after 2 h compared to levels in sham controls and rats exposed to a single blast [27]. By day 22 post-injury, animals exposed to either a single blast or multiple blasts had significantly higher levels of VEGF, neuron-specific enolase (NSE), neurofilament H (NFH), and GFAP than did those in the noninjured control groups [27]. At 1 day post-blast exposure, increased GFAP immunoreactivity was observed in the hippocampus of animals exposed to a single blast, whereas no such increase was seen in animals exposed to multiple blasts [27].…”

“…By day 22 post-injury, animals exposed to either a single blast or multiple blasts had significantly higher levels of VEGF, neuron-specific enolase (NSE), neurofilament H (NFH), and GFAP than did those in the noninjured control groups [27]. At 1 day post-blast exposure, increased GFAP immunoreactivity was observed in the hippocampus of animals exposed to a single blast, whereas no such increase was seen in animals exposed to multiple blasts [27]. However, by day 22, an apparent increase in GFAP immunoreactivity was observed in the hippocampus of the multiple blast-exposed rats.…”

Mission Connect Mild TBI Translational Research Consortium: To Study the Role of IL-1 and TNF Receptor Activation in Neurological Deficits after TBI

“…Mild traumatic brain injuries (mTBI) are common among our military personnel (Hogue et al, 2008;Kamnash et al, 2012), of these mild blast brain injuries (mBBI) are responsible for over 80% of casualties in the last decade (Levin et al, 2010). Mild "blast" injuries due to improvised exploding devices have long term cognitive and behavioral deficits due to what has been labeled as mild traumatic brain injury (mTBI).…”