Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Rodriguez, Uylissa A.; Zeng, Yaping; Parsley, Margaret A.; Hawkins, Bridget E.; Prough, Donald S.; DeWitt, Douglas S.

doi:10.3791/58792

Cited by 5 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The BBB, for example, is an essential element in brain homeostasis and is one of the first sites to be altered following bTBI, and is a structure particularly vulnerable to impact compression ( Gama Sosa et al, 2014 ; Huber et al, 2016 ). Acute cerebral vascular impairment and BBB protein dysregulation have been reported after single and multiple ABS exposure, respectively ( Heyburn et al, 2019 , 2021 ; Rodriguez et al, 2019 ), and our data support these findings with acute BBB permeability to Evans blue 4 h following ABS. Finite element modeling and shock tube experiments demonstrate that the prone orientation produces a lesser degree of damage compared to other body orientations ( Hubbard et al, 2014 ; Heyburn et al, 2019 ; Unnikrishnan et al, 2021 ).…”

Section: Discussionsupporting

confidence: 89%

Limbic Responses Following Shock Wave Exposure in Male and Female Mice

McNamara

Tucker²,

Liu³

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Blast traumatic brain injury (bTBI) presents a serious threat to military personnel and often results in psychiatric conditions related to limbic system dysfunction. In this study, the functional outcomes for anxiety- and depressive-like behaviors and neuronal activation were evaluated in male and female mice after exposure to an Advanced Blast Simulator (ABS) shock wave. Mice were placed in a ventrally exposed orientation inside of the ABS test section and received primary and tertiary shock wave insults of approximately 15 psi peak pressure. Evans blue staining indicated cases of blood-brain barrier breach in the superficial cerebral cortex four, but not 24 h after blast, but the severity was variable. Behavioral testing with the elevated plus maze (EPM) or elevated zero maze (EZM), sucrose preference test (SPT), and tail suspension test (TST) or forced swim test (FST) were conducted 8 days–3.5 weeks after shock wave exposure. There was a sex difference, but no injury effect, for distance travelled in the EZM where female mice travelled significantly farther than males. The SPT and FST did not indicate group differences; however, injured mice were less immobile than sham mice during the TST; possibly indicating more agitated behavior. In a separate cohort of animals, the expression of the immediate early gene, c-Fos, was detected 4 h after undergoing bTBI or sham procedures. No differences in c-Fos expression were found in the cerebral cortex, but female mice in general displayed enhanced c-Fos activation in the paraventricular nucleus of the thalamus (PVT) compared to male mice. In the amygdala, more c-Fos-positive cells were observed in injured animals compared to sham mice. The observed sex differences in the PVT and c-Fos activation in the amygdala may correlate with the reported hyperactivity of females post-injury. This study demonstrates, albeit with mild effects, behavioral and neuronal activation correlates in female rodents after blast injury that could be relevant to the incidence of increased post-traumatic stress disorder in women.

show abstract

Section: Discussionsupporting

confidence: 89%

Limbic Responses Following Shock Wave Exposure in Male and Female Mice

McNamara

Tucker²,

Liu³

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“… 44 Similar ABS exposures can alter the cerebral vasculature and the blood–brain barrier. 41 , 42 Blast exposure can also alter cellular pathology including expression of markers for gliosis and myelinated axons (CNPase and neurofilament H), but appears to vary with the degree of head immobilization. 43 Indeed, single ABS exposure at 15 psi using a mesh to position the mouse in the prone position and minimize head movement resulted in a low-level blast frontal exposure that did not induce detectable microglial activation in the CC.…”

Section: Discussionmentioning

confidence: 99%

“…To model the blast wave component of low-level exposures to explosives or heavy artillery, the current experiments used an ABS device to generate controlled high-fidelity simulation of both positive and negative phases of ''free-field'' blast. 33,[41][42][43][44] Studies using singleblast exposures in the ABS in adult rats have produced long-term behavioral effects. 44 Similar ABS exposures can alter the cerebral vasculature and the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

Repetitive Blast Exposure Produces White Matter Axon Damage without Subsequent Myelin Remodeling: In Vivo Analysis of Brain Injury Using Fluorescent Reporter Mice

Bradshaw

Kim

et al. 2021

Neurotrauma Reports

View full text Add to dashboard Cite

The potential effects of blast exposure on the brain health of military personnel have raised concerns and led to increased surveillance of blast exposures. Neuroimaging studies have reported white matter abnormalities in brains of service members with a history of blast exposure. However, blast effects on white matter microstructure remain poorly understood. As a novel approach to screen for white matter effects, transgenic mice that express fluorescent reporters to sensitively detect axon damage and myelin remodeling were exposed to simulated repetitive blasts (once/day on 5 consecutive days). Axons were visualized using Thy1-YFP-16 reporter mice that express yellow fluorescent protein (YFP) in a broad spectrum of neurons. Swelling along damaged axons forms varicosities that fill with YFP. The frequency and size of axonal varicosities were significantly increased in the corpus callosum (CC) and cingulum at 3 days after the final blast exposure, versus in sham procedures. CC immunolabeling for reactive astrocyte and microglial markers was also significantly increased. NG2CreER;mTmG mice were given tamoxifen (TMX) on days 2 and 3 after the final blast to induce fluorescent labeling of newly synthesized myelin membranes, indicating plasticity and/or repair. Myelin synthesis was not altered in the CC over the intervening 4 or 8 weeks after repetitive blast exposure. These experiments show the advantages of transgenic reporter mice for analysis of white matter injury that detects subtle, diffuse axon damage and the dynamic nature of myelin sheaths. These results show that repetitive low-level blast exposures produce infrequent but significant axon damage along with neuroinflammation in white matter.

show abstract