scholarly journals Long-term cognitive impairment without diffuse axonal injury following repetitive mild traumatic brain injury in rats

2019 ◽  
Author(s):  
Sai Ambika Tadepalli ◽  
Zsolt Kristóf Bali ◽  
Nóra Bruszt ◽  
Lili Veronika Nagy ◽  
Krisztina Amrein ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Cognitive Abilities ◽  
Brain Injuries ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Poor Performance ◽  
Suitable Model ◽  
Post Injury ◽  
Object Recognition Test

AbstractRepetitive mild traumatic brain injuries (TBI) impair cognitive abilities and increase risk of neurodegenerative disorders in humans. We developed two repetitive mild TBI models in rats with different time intervals between successive weight-drop injuries, and assessed cognitive performance and biomarker profiles. Rats were subjected to repetitive Sham (no injury), single mild (mTBI), repetitive mild (rmTBI – 5 hits, 24 h apart), rapid repetitive mild (rapTBI – 5 hits, 5 min apart) and single severe (sTBI) TBI. We assessed cognitive performance 2 and 8 weeks after TBI in the novel object recognition test (NOR), and 6-7 weeks after TBI in the water maze (MWM). Acute immunohistochemical markers were checked 24 h after TBI, and blood biomarkers were measured with ELISA 8 weeks after TBI. In the NOR, both rmTBI and rapTBI showed poor performance at 2 weeks post-injury. At 8 weeks post-injury, the rmTBI group still performed worse than the Sham and mTBI groups, while the rapTBI group recovered. In the MWM, the rapTBI group performed worse than Sham and mTBI. Acute APP and RMO-14 immunohistochemistry showed axonal injury at the pontomedullary junction in the sTBI, but not in other groups. ELISA showed increased serum GFAP levels 8 weeks after sTBI, while no differences were found between the injury groups in the levels of phosphorylated-tau and S100β. Results suggest that the rmTBI protocol is the most suitable model for testing cognitive impairment after mild repetitive head injuries. The lack of common biomarkers suggests novel unknown underlying mechanisms of rmTBI.

Diffuse Axonal Injury and Degradation in Mechanical Characteristics of Brain White Matter

2008 ◽  
Author(s):  
Nabi Abolfathi ◽  
Abhai Naik ◽  
Mahdi Sotudeh ◽  
Ghodrat Karami ◽  
Mariusz Ziejewski
Keyword(s):  
Brain Tissue ◽  
Fibrous Composite ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Viscoelastic Behavior ◽  
Severe Disabilities ◽  
Post Injury ◽  
Brain White Matter ◽  
Injured Brain

Diffuse Axonal Injury (DAI) can happen due to sudden motions of head and is one of the major causes of fatality and severe disabilities. To study DAI, any change in material characteristics of brain tissue post injury needs to be well understood. In this study, the focus will be on changes in the viscoelastic material properties of white mater in the brain due to DAI resulting in axonal disconnections. Using a micromechanics fibrous composite modeling for white mater, we have developed an algorithm to analyze the effect of discontinuity due to breakage of axons inside the surrounded matrix. Repeated unit cell (RUC) was assumed to represent the axonal distribution within the extracellular matrix. Relaxation test were conducted for characterization of the viscoelastic behavior. The result of this study provides a modeling technique for characterization of injured brain tissue in white mater and proposes necessity of including the appropriate post injury axonal mechanical properties. These findings can improve the understanding of injury from mechanical perspective and help in predicting vulnerability of any such injured tissue against further injuries.

scholarly journals A Conceptual Overview of Axonopathy in Infants and Children with Allegedly Inflicted Head Trauma

2016 ◽  
Vol 6 (4) ◽  
pp. 608-621
Author(s):  
Vivian S. Snyder ◽  
Lawrence A. Hansen
Keyword(s):  
White Matter ◽  
Head Trauma ◽  
Forensic Pathology ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Infants And Children ◽  
Post Injury ◽  
Controversial Topic ◽  
Definition Of ◽  
Medical Disciplines

Fatal, allegedly inflicted pediatric head trauma remains a controversial topic in forensic pathology. Recommendations for systematic neuropathologic evaluation of the brains of supposedly injured infants and children usually include the assessment of long white matter tracts in search of axonopathy — specifically, diffuse axonal injury. The ability to recognize, document, and interpret injuries to axons has significant academic and medicolegal implications. For example, more than two decades of inconsistent nosology have resulted in confusion about the definition of diffuse axonal injury between various medical disciplines including radiology, neurosurgery, pediatrics, neuropathology, and forensic pathology. Furthermore, in the pediatric setting, acceptance that “pure” shaking can cause axonal shearing in infants and young children is not widespread. Additionally, controversy abounds whether or not axonal trauma can be identified within regions of white matter ischemia — a debate with very significant implications. Immunohistochemistry is often used not only to document axonal injury, but also to estimate the time since injury. As a result, the estimated post-injury interval may then be used by law enforcement officers and prosecutors to narrow “exclusive opportunity” and thus, identify potential suspects. Fundamental to these highly complicated and controversial topics is a philosophical understanding of the diffuse axonal injury spectrum disorders.

281 Predicting neurodegeneration after traumatic brain injury

2018 ◽  
Vol 89 (10) ◽  
pp. A42.1-A42
Author(s):  
Graham Neil SN ◽  
Jolly Amy E ◽  
Bourke Niall J ◽  
Scott Gregory ◽  
Cole James H ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Brain Atrophy ◽  
Diffusion Tensor ◽  
Chronic Traumatic Encephalopathy ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Jacobian Determinant ◽  
Post Injury

BackgroundDementia rates are elevated after traumatic brain injury (TBI) and a subgroup develops chronic traumatic encephalopathy. Post-traumatic neurodegeneration can be measured by brain atrophy rates derived from neuroimaging, but it is unclear how atrophy relates to the initial pattern of injury.ObjectivesTo investigate the relationship between baseline TBI patterns and subsequent neurodegeneration measured by progressive brain atrophy.Methods55 patients after moderate-severe TBI (mean 3 years post-injury) and 20 controls underwent longitudinal MRI. Brain atrophy was quantified using the Jacobian determinant defined from volumetric T1 scans approximately one year apart. Diffuse axonal injury was measured using diffusion tensor imaging and focal injuries defined from T1 and FLAIR. Neuropsychological assessment was performed.ResultsAbnormal progressive brain atrophy was seen after TBI (~1.8%/year in white matter). This was accompanied by widespread reductions in fractional anisotropy, in keeping with the presence of diffuse axonal injury. There was a strong negative correlation between FA and brain atrophy, whereby areas of greater white matter damage showed greater atrophy over time.ConclusionsThe results show a strong relationship between the location of diffuse axonal injury and subsequent neurodegeneration. This suggests that TBI triggers progressive neurodegeneration through the long-lasting effects of diffuse axonal injury.

Simulating Axonal Stretch During Traumatic Brain Injury Events

2010 ◽  
Author(s):  
Jean-Pierre Dollé ◽  
Jeffrey Barminko ◽  
Rene Schloss ◽  
Martin L. Yarmush
Keyword(s):  
Brain Injuries ◽  
Motor Vehicle ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
The United States ◽  
Motor Vehicle Accidents ◽  
Inertial Forces ◽  
Vehicle Accidents ◽  
Rapid Deceleration ◽  
The Brain

Traumatic Brain Injuries (TBI) affect up to 1.5 million people annually within the United States with as many as 250,000 being hospitalized and 50,000 dying [1]. TBI events occur when the brain experiences a sudden trauma such as a rapid deceleration of the brain that typically occurs during motor vehicle accidents. During rapid deceleration events, the brain is subjected to high inertial forces that can result in a shearing or elongation of axons that is commonly known as Diffuse Axonal Injury (DAI) [2,3].

scholarly journals Corpus Callosum Pathology as a Potential Surrogate Marker of Cognitive Impairment in Diffuse Axonal Injury

2016 ◽  
Vol 28 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Shiho Ubukata ◽  
Keita Ueda ◽  
Genichi Sugihara ◽  
Walid Yassin ◽  
Toshihiko Aso ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Corpus Callosum ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Surrogate Marker

scholarly journals A Delayed Presentation of Diffuse Axonal Injury

2021 ◽  
Author(s):  
Meaghan Wunder ◽  
Kara Ruicci
Keyword(s):  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Neurological Status ◽  
Axonal Damage ◽  
Delayed Presentation ◽  
Post Injury ◽  
Current Case ◽  
Lower Leg Fracture ◽  
The Brain ◽  
Leg Fracture

Diffuse axonal injury is one of the most common and debilitating pathologies resulting from mechanical deformation of the brain.  The current case involves a 19-year-old female involved in a high velocity ski crash. The accident resulted in a right lower leg fracture, with no loss of consciousness or evidence of head trauma.  Approximately 6.5 hours after her admission, the neurological status of the patient deteriorated markedly, and magnetic resonance imaging findings were consistent with diffuse axonal injury.  This presentation illustrates a case of delayed diffuse axonal injury, a phenomenon not commonly described.  Diffuse axonal injury involves rapid inertial forces causing strain to brain tissue.  This strain results in various stages of diffuse axonal damage and inflammation.  This article highlights a case of delayed onset diffuse axonal injury, describes the progression of neural sequelae post-injury resulting in axonal damage and explores proposed therapeutic targets. 

scholarly journals Dynamin and reverse-mode sodium calcium exchanger blockade confers neuroprotection from diffuse axonal injury

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Anton Omelchenko ◽  
Anil B. Shrirao ◽  
Atul K. Bhattiprolu ◽  
Jeffrey D. Zahn ◽  
Rene S. Schloss ◽  
...  
Keyword(s):  
Cell Damage ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Health Concern ◽  
Supporting Evidence ◽  
Post Injury ◽  
Sodium Calcium ◽  
Secondary Damage ◽  
Human Pathology

Abstract Mild traumatic brain injury (mTBI) is a frequently overlooked public health concern that is difficult to diagnose and treat. Diffuse axonal injury (DAI) is a common mTBI neuropathology in which axonal shearing and stretching induces breakdown of the cytoskeleton, impaired axonal trafficking, axonal degeneration, and cognitive dysfunction. DAI is becoming recognized as a principal neuropathology of mTBI with supporting evidence from animal model, human pathology, and neuroimaging studies. As mitochondrial dysfunction and calcium overload are critical steps in secondary brain and axonal injury, we investigated changes in protein expression of potential targets following mTBI using an in vivo controlled cortical impact model. We show upregulated expression of sodium calcium exchanger1 (NCX1) in the hippocampus and cortex at distinct time points post-mTBI. Expression of dynamin-related protein1 (Drp1), a GTPase responsible for regulation of mitochondrial fission, also changes differently post-injury in the hippocampus and cortex. Using an in vitro model of DAI previously reported by our group, we tested whether pharmacological inhibition of NCX1 by SN-6 and of dynamin1, dynamin2, and Drp1 by dynasore mitigates secondary damage. Dynasore and SN-6 attenuate stretch injury-induced swelling of axonal varicosities and mitochondrial fragmentation. In addition, we show that dynasore, but not SN-6, protects against H2O2-induced damage in an organotypic oxidative stress model. As there is currently no standard treatment to mitigate cell damage induced by mTBI and DAI, this work highlights two potential therapeutic targets for treatment of DAI in multiple models of mTBI and DAI.

scholarly journals Diffuse Axonal Injury in the Rat Brain: Axonal Injury and Oligodendrocyte Activity Following Rotational Injury

2020 ◽  
Vol 10 (4) ◽  
pp. 229
Author(s):  
Michela Losurdo ◽  
Johan Davidsson ◽  
Mattias K. Sköld
Keyword(s):  
Cell Injury ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Angular Acceleration ◽  
Cell Loss ◽  
Oligodendrocyte Progenitor Cells ◽  
Dorsal Cortex ◽  
Post Injury ◽  
Adult Rats ◽  
Neuronal Stress

Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope® to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.

scholarly journals Axons-on-a-Chip for Mimicking Non-Disruptive Diffuse Axonal Injury underlying Traumatic Brain Injury

2021 ◽  
Author(s):  
Wei Li ◽  
Haofei Wang ◽  
Xiaorong Pan ◽  
Dejan Gagoski ◽  
Nela Durisic ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mechanical Stress ◽  
Brain Injuries ◽  
Early Stage ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Clear Correlation ◽  
Pathological Feature ◽  
Intracellular Changes

Diffuse axonal injury (DAI) is the most severe pathological feature of traumatic brain injury. However, how primary axonal injury is induced by mechanical stress and whether it could be mitigated remain unknown, largely due to the resolution limits of medical imaging approaches. Here we established an Axon-on-a-Chip (AoC) model for mimicking DAI and investigating its early cellular responses. By integrating computational fluid dynamics and microfluidic techniques, DAI was observed for the first time during mechanical stress, and a clear correlation between stress intensity and severity of DAI was elucidated. This AoC was further used to investigate the dynamic intracellular changes occurring simultaneously with stress, and identified delayed local Ca2+ surges escorted rapid disruption of periodic axonal cytoskeleton during the early stage of DAI. Compatible with high-resolution live-microscopy, this model hereby provides a versatile system to identify early mechanisms underlying DAI, offering a platform for screening effective treatments to alleviate brain injuries.

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