A Novel Closed-Head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice

Heldt, Scott A.; Elberger, Andrea J.; Deng, Yunping; Guley, Natalie; Mar, Nobel Dvm Del; Rogers, Joshua Ms; Choi, Gy Won; Ferrell, Jessica M.; Rex, Tonia S.; Honig, Marcia G.; Reiner, Anton

doi:10.3389/fneur.2014.00002

Cited by 85 publications

(114 citation statements)

References 76 publications

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“…41,42 Thus, in the progeny of a cross between a floxed Thy1-EYFP reporter mouse and an emx1-Cre driver mouse, nearly all excitatory cortical and many amygdalar neurons express EYFP. [41][42][43] Although emx1 has not been reported to be expressed in the retina, we found that about 5% of retinal ganglion cells also express EYFP. The floxed Thy1-EYFP reporter mice (purchased from JAX) and emx1-Cre driver mice (purchased from the Mutant Mouse Regional Resource Consortium, or MMRRC) were maintained as colonies at the University of Tennessee Health Science Center (UTHSC).…”

Section: Animalscontrasting

confidence: 55%

“…The overpressure air blast is delivered by a small horizontally mounted air cannon system, 40,43 consisting of a modified paintball gun (Invert Mini, Empire Paintball, Sewell, NJ), pressurized air tank, and x-y table secured onto a medium-density fiberboard (Fig. 1).…”

Section: Tbi Methodsmentioning

confidence: 99%

“…In addition to the 7.5-mm hole that faces the gun barrel, the outer tube possesses an 11-mm hole on the opposite side, allowing the barrel of a model STJE Sensotec pressure transducer (Honeywell, Morristown, NJ) to be inserted so the barrel tip is in the same position that the mouse head occupies during blast. 40,43 The pressures detected by this transducer are recorded and analyzed using Labview software (National Instruments, Austin, TX). This makes it possible to measure the air blast pressure at the position occupied by the mouse head during a blast session.…”

Section: Tbi Methodsmentioning

confidence: 99%

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A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Guley

Rogers

Mar

et al. 2016

Journal of Neurotrauma

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104

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Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

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Section: Animalscontrasting

confidence: 55%

Section: Tbi Methodsmentioning

confidence: 99%

Section: Tbi Methodsmentioning

confidence: 99%

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A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Guley

Rogers

Mar

et al. 2016

Journal of Neurotrauma

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104

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“…The causes of mTBI are currently unknown, and there is no consensus in the literature of injury mechanisms resulting in mTBI as a result of blast, which further emphasizes the need for additional research in the topic. Theories of possible injury mechanisms caused by overpressure exposure include soft-tissue damage from shearing [4][5][6][7], distortion of cellular structures and cell death in the brain [5,[8][9][10][11][12][13][14], and intracranial fluid cavitation [5,[15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Polymeric Hopkinson Bar-Confinement Chamber Apparatus to Evaluate Fluid Cavitation

2017

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Mild traumatic brain injury associated with blast exposure is an important issue, and cavitation of the cerebrospinal fluid (CSF) has been suggested as a potential injury mechanism; however, physical measurements are required to evaluate cavitation thresholds. Modifications to a Split Hopkinson Pressure Bar (SHPB) apparatus were investigated with the aim to generate localized fluid cavitation and measure the cavitation threshold of fluids. The proposed design incorporated a novel closed cavitation chamber to generate localized cavitation resulting from a reflected compression pulse, which was generated by a spherical steel striker and Polymethyl methacrylate (PMMA) incident bar. A numerical model of the incident bar was developed and validated with 24 independent tests (cross-correlation: 0.970-0.997), and this was extended to a numerical model of the apparatus including the chamber, validated with 27 independent tests (cross-correlation: 0.921) to predict the tensile fluid pressure in the chamber. Tests on distilled water were performed with comparable numerical results for the chamber strain (R 2 : 0.875) and chamber end-wall velocity (R 2 : 0.992). The pressure in the chamber was determined from the model to avoid introducing a nucleation site via a pressure gauge, and was verified with a firstorder approximation showing good agreement (R 2 : 0.892). The 50% probability of cavitation for distilled water was −3.32 MPa ±3%, comparable to values in the literature. This novel apparatus, including a closed confinement chamber integrated with a polymeric SHPB apparatus was able to create localized fluid cavitation with loading comparable to blast exposure. Future studies will include the measurement of CSF cavitation pressure.

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“…However, it is difficult to diagnose mTBI by conventional MRI. Additionally, CT and conventional MRI performance is not strongly correlated with the severity and prognosis of patients constantly (9)(10)(11). Thus, it is essential to find suitable method or biomarkers to detect mTBI.…”

Section: Introductionmentioning

confidence: 99%

Preliminary Study of Diffusion Kurtosis Imaging in Mild Traumatic Brain Injury

Zhang

Jin

et al. 2018

Iran J Radiol

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Background: Traumatic brain injury (TBI) can result from blunt trauma or acceleration/deceleration force and is considered to be one of the most important public health problems. Many patients of TBI lose professional competence and independence. They may eventually suffer serious sequelae, such as cognitive impairment, memory loss, and long-term headache. In craniocerebral trauma patients, mild traumatic brain injury accounts for 70% -80% of the cases. Early diagnosis and intervention can decrease the post-concussional sequelae for mild TBI (mTBI). Objectives: To investigate the value of diffusion kurtosis imaging (DKI) in mild traumatic brain injury (mTBI) patients. Patients and Methods: Conventional MRI sequences (T1 and T2 weighted images) and DKI scans of 25 healthy controls and 24 mTBI patients were obtained. Regions of interests (ROIs) were drawn and analyzed on several planes including white matter, deep gray matter nuclei, peri-contusion and contusion lesion on fused fractional anisotropy (FA), mean diffusion (MD) maps, and mean kurtosis (MK) maps, respectively. FA, MD, and MK values were measured in a certain region (he area of bilateral centrum semiovale (CS), corona radiate (CR), caudate nucleus head (CNH), genu of corpus callosum (CCG), corpus callosum splenium (CCS), anterior limb of the internal capsule (ALIC), posterior limb of internal capsule (PLIC), external capsule (EC), lenticular nucleus (LN), and thalamus). Student's t test was used to compare the average values of FA, MD, and MK between mTBI patients and healthy controls. Paired t-test was also used to compare contusion lesions and mirror symmetrical areas. Results: FA and MK values were significantly different in all of the white matter and grey matter, while MD values among the various ROIs were insignificantly different in the healthy control group. In mTBI patients, the FA values of genu of corpus callosum, splenium of corpus callosum, and external capsule were decreased. Whereas, MD value of genu of corpus callosum in trauma group was increased. Except for the head of the caudate nucleus and posterior limb of the internal capsule, the MK values of the rest of the ROIs in the trauma group decreased significantly. Moreover, compared with the contra-lateral, there were more significant contusion lesions of FA and MK reductions than increased MD values. FA and MD values of peri-contusion had no significant difference compared with the contra-lateral while MK values decreased significantly. Conclusion: Compared with conventional MRI sequences, DKI can detect micro white matter injury, and MK parameter is more sensitive than FA and MD. In addition, DKI can find these changes not only in the white matter but also in deep gray matter nucleus, making it a promising imaging tool to assist the detection of mild traumatic brain injury.

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A Novel Closed-Head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice

Cited by 85 publications

References 76 publications

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Polymeric Hopkinson Bar-Confinement Chamber Apparatus to Evaluate Fluid Cavitation

Preliminary Study of Diffusion Kurtosis Imaging in Mild Traumatic Brain Injury

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