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 ◽  
...  

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.

Author(s):  
Jean-Pierre Dolle ◽  
Rene Schloss ◽  
Martin L. Yarmush

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 acc/deceleration. These events produce high inertial forces that result in a shearing or elongation of axons (commonly known as Diffuse Axonal Injury [2].


2011 ◽  
Vol 153 (8) ◽  
pp. 1687-1694 ◽  
Author(s):  
Hidetoshi Matsukawa ◽  
Masaki Shinoda ◽  
Motoharu Fujii ◽  
Osamu Takahashi ◽  
Daisuke Yamamoto ◽  
...  

2018 ◽  
Vol 89 (10) ◽  
pp. A42.1-A42
Author(s):  
Graham Neil SN ◽  
Jolly Amy E ◽  
Bourke Niall J ◽  
Scott Gregory ◽  
Cole James H ◽  
...  

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.


2010 ◽  
Vol 3 (2) ◽  
pp. 111
Author(s):  
Hyung Jong Choi ◽  
Jong-Gu Kang ◽  
Seung Ho Ahn ◽  
Suk Hoon Ohn ◽  
Kwang-Ik Jung ◽  
...  

2015 ◽  
Vol 32 (5) ◽  
pp. 359-365 ◽  
Author(s):  
Daddy Mata-Mbemba ◽  
Shunji Mugikura ◽  
Atsuhiro Nakagawa ◽  
Takaki Murata ◽  
Yumiko Kato ◽  
...  

2007 ◽  
Vol 45 (14) ◽  
pp. 3149-3156 ◽  
Author(s):  
Matthias L. Schroeter ◽  
Barbara Ettrich ◽  
Christiane Schwier ◽  
Rainer Scheid ◽  
Thomas Guthke ◽  
...  

2014 ◽  
Vol 3 (1) ◽  
pp. 35 ◽  
Author(s):  
SalmanAbbasi Fard ◽  
MajidRezvani Habibabadi ◽  
Payam Moein ◽  
Morteza Naderan ◽  
Rasoul Norouzi ◽  
...  

2018 ◽  
Vol 77 (9) ◽  
pp. 782-792 ◽  
Author(s):  
Yasuaki Ogino ◽  
Michal Vascak ◽  
John T Povlishock

Abstract Mild traumatic brain injury (mTBI) has been linked to enduring neurological damage following repetitive injury. Previously, we reported that intensity-specific, repetitive mTBI exacerbated microvascular and axonal damage in brainstem. For a more rigorous and global assessment, we assessed the burden of neocortical diffuse axonal injury (DAI) evoked by repetitive mTBI. Mice were subjected to mild central fluid percussion injuries at 1.4 and 1.6 atm with or without repetitive insult at a 3-hour interval and killed at 24 hours postinjury. Neocortical DAI within layer V was quantitatively assessed by double-labeling p-c-Jun and NeuN to identify both the axotomized and total neuronal population. Both confocal and electron microscopic findings revealed no apparent evidence of neuronal death. Repetitive mTBI of 1.6 atm group, but not of 1.4 atm group, demonstrated a significantly higher proportion of axotomized neurons. These results demonstrate that different intensities of mTBI induced different burdens of DAI after repetitive insult. Interestingly, the parallel loss of the righting reflex reflected differences in injury intensity, yet the duration of this reflex was not elongated by the repetitive insult. These data highlight some of the complex issues surrounding repetitive mTBI and its associated morbidity, mandating the need for continued exploration.


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