Selective vulnerability of the cerebral vasculature to blast injury in a rat model of mild traumatic brain injury

Abstract

BackgroundBlast-related traumatic brain injury (TBI) is a common cause of injury in the military operations in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. The aim of the present study was to examine whether blast exposure affects the cerebral vasculature in a rodent model. We analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24 hours or between 6 and 10 months after exposure. Blast-induced cerebral vascular pathology was examined by a combination of light microscopy, immunohistochemistry, and electron microscopy.ResultsWe describe a selective vascular pathology that is present acutely at 24 hours after injury. The vascular pathology is found at the margins of focal shear-related injuries that, as we previously showed, typically follow the patterns of penetrating cortical vessels. However, changes in the microvasculature extend beyond the margins of such lesions. Electron microscopy revealed that microvascular pathology is found in regions of the brain with an otherwise normal neuropil. This initial injury leads to chronic changes in the microvasculature that are still evident many months after the initial blast exposure.ConclusionsThese studies suggest that vascular pathology may be a central mechanism in the induction of chronic blast-related injury.

Effects of Exposure to Blast Overpressure on Intracranial Pressure and Blood-Brain Barrier Permeability in a Rat Model

“…It was reported that the earliest pathological findings after 24 h of exposure to blast are the presence of blood in ventricles and choroid plexus [31, 32]. This occurs even after exposures to mild blast intensities (74.5 kPa) which can be attributed to the direct shearing effects of blast on the choroid plexus leading to vascular rupture and leakage of blood into the ventricles.…”

“…Confocal images have shown strong widespread EB fluorescence in cortex after blast [14] and the optical density of EB in frontal cortex of blast group was over 60% higher than the sham group [11]. It was reported that focal lesions were present in many brain regions including the cortex, which were likely caused by direct shear effects induced by blast [31, 32]. Both, changes in ICP and EB leakage were related to the BOP intensity with a more pronounced effect observed in multiple exposures to the higher levels of BOP.…”

A mouse Model of Focal Vascular Injury Induces Astrocyte Reactivity, Tau Oligomers, and Aberrant Behavior

“…Recently, our group has also shown an upregulation of pro-inflammatory markers in a rat model of blast injury (16). A significant difference in iNOS mRNA abundance was observed in the ipsilateral S1BF region after blast (F (2, 12) = 5.60; P < 0.05). We revealed a significant increase in iNOS mRNA abundance at 24 hours post-blast when compared to control animals (q = 3.21; P < 0.05) (Figure 7A).…”

“…A significant difference in GFAP mRNA abundance was observed in the ipsilateral S1BF region after blast (F (2, 12) = 5.73; P < 0.05). We revealed a significant increase in GFAP mRNA abundance at 24 hours post-blast when compared to control animals (q = 3.36; P < 0.05) (Figure 5A).…”

“…Recent evidence suggests that blood-brain barrier (BBB) disruption exacerbates the initial injury and increases inflammation following neurotrauma (2). BBB disruption can lead to robust oxidative stress (3), and contribute to persistent inflammation (4).…”