<i>In Vitro</i>Models of Traumatic Brain Injury: A Systematic Review

Wu, Yihan; Rosset, Samuel; Lee, Tae-rin; Dragunow, Mike; Park, Thomas; Shim, Vickie

doi:10.1089/neu.2020.7402

Cited by 32 publications

(32 citation statements)

References 141 publications

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“…Among various types of mechanical forces, uniaxial stretch was postulated as the major force to induce DAI [ 3 – 7 ]. In fact, uniaxial stretch was the most frequently used way of load application among all TBI in vitro models published in the past decade or so [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Many in vivo and in vitro model systems have been developed to study various aspects of TBI [ 19 , 20 ], but cross-system studies are still very limited, hindering a better understanding of the core mechanism underlying CNS mechanosensation and injury. In the present study, by comparing two mTBI mouse models, we discovered that mechanical impact indeed induced axonal varicosity formation in mouse brains immediately after mechanical impact, representing the earliest subcellular event known in mTBI.…”

Section: Introductionmentioning

confidence: 99%

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Immediate induction of varicosities by transverse compression but not uniaxial stretch in axon mechanosensation

Sun

Cheng

et al. 2022

acta neuropathol commun

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Uniaxial stretch is believed to drive diffuse axonal injury (DAI) in mild traumatic brain injury (mTBI). Axonal varicosities are enlarged structures along axonal shafts and represent a hallmark feature of DAI. Here we report that axonal varicosities initiate in vivo immediately after head impact and are mainly induced by transverse compression but not uniaxial stretch. Vertical and lateral impacts to the mouse head induced axonal varicosities in distinct brain regions before any changes of microglial markers. Varicosities preferentially formed along axons perpendicular to impact direction. In cultured neurons, whereas 50% uniaxial strain was needed to rapidly induce axonal varicosities in a nanowrinkled stretch assay, physiologically-relevant transverse compression effectively induced axonal varicosities in a fluid puffing assay and can generate large but nonuniform deformation simulated by finite element analysis. Therefore, impact strength and direction may determine the threshold and spatial pattern of axonal varicosity initiation, respectively, partially resulting from intrinsic properties of axon mechanosensation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immediate induction of varicosities by transverse compression but not uniaxial stretch in axon mechanosensation

Sun

Cheng

et al. 2022

acta neuropathol commun

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“…This occurrence is accompanied by an increased probability and earlier onset of dementias in elderly TBI patients 9 , 10 . Although, not reflecting the full complexity of the brain pathology, in vitro trauma models allow for repeatable and controlled experiments, and agree well with in vivo TBI models 62 – 64 . Transection/scratch models, like ours, are well-established, simple to perform and produce precise injuries of reproducible levels.…”

Section: Discussionmentioning

confidence: 65%

Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy

Streubel-Gallasch

Zyśk

Beretta

et al. 2021

Sci Rep

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Traumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the connection between TBI and Alzheimer’s disease in the aged brain and potential exacerbating factors is still evolving. The aim of this study was to investigate cellular injury-induced processes in the presence of amyloid β (Aβ) pathology. For this purpose, a co-culture system of cortical stem-cell derived astrocytes, neurons and oligodendrocytes were exposed to Aβ42 protofibrils prior to a mechanically induced scratch injury. Cellular responses, including neurodegeneration, glial activation and autophagy was assessed by immunoblotting, immunocytochemistry, ELISA and transmission electron microscopy. Our results demonstrate that the combined burden of Aβ exposure and experimental TBI causes a decline in the number of neurons, the differential expression of the key astrocytic markers glial fibrillary acidic protein and S100 calcium-binding protein beta, mitochondrial alterations and prevents the upregulation of autophagy. Our study provides valuable information about the impact of TBI sustained in the presence of Aβ deposits and helps to advance the understanding of geriatric TBI on the cellular level.

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“…As described previously [25,26], scratch injury, a widely accepted method, was used to establish an in vitro model of TBI. In brief, a sterile pipette tip (10 μl) was used to manually scratch the culture.…”

Section: Establishment Of An In Vitro Model Of Scratch Injurymentioning

confidence: 99%

Armcx1 Alleviates Secondary Brain Injury After Traumatic Brain Injury by Reducing Apoptosis and Axonal Injury in a Mouse Model of Controlled Cortical Impact

Wang

Liu

et al. 2021

Preprint

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Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport. Mitochondrial transport promotes the removal of damaged mitochondria and the replenishment of healthy mitochondria, which are essential for neuronal survival after traumatic brain injury (TBI). This study investigated the role of Armcx1 and its underlying regulator(s) in secondary brain injury (SBI) after TBI. An in vivo TBI model was established in C57BL/6 mice via controlled cortical impact (CCI). Adeno-associated viruses with Armcx1 overexpression and knockdown were constructed and administered to mice by stereotactic cortical injection. Exogenous miR-223-3P mimic or inhibitor was transfected into cultured cortical neurons, which were then scratched to simulate TBI in vitro. The Armcx1 protein level was found to be decreased in peri-lesion tissue, particularly in neurons. The overexpression of Armcx1 significantly reduced TBI-induced neurological dysfunction, apoptosis, axonal injury, and mitochondrial dysfunction, while knockdown of Armcx1 had the opposite effect. Armcx1 was a direct target of miR-223-3P. The miR-223-3P mimic significantly reduced the Armcx1 protein level, while the miR-223-3P inhibitor had the opposite effect. Finally, the miR-223-3P inhibitor significantly improved mitochondrial membrane potential and increased the total length of the neurites without affecting branching numbers, while the miR-223-3P mimic had the opposite effect. In summary, our results suggest that the decreased expression of Armcx1 protein in neurons after experimental TBI aggravates secondary brain injury, which may be regulated by miR-223-3P. Therefore, this study provides a potential therapeutic approach for treating TBI.

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In VitroModels of Traumatic Brain Injury: A Systematic Review

Cited by 32 publications

References 141 publications

Immediate induction of varicosities by transverse compression but not uniaxial stretch in axon mechanosensation

Immediate induction of varicosities by transverse compression but not uniaxial stretch in axon mechanosensation

Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy

Armcx1 Alleviates Secondary Brain Injury After Traumatic Brain Injury by Reducing Apoptosis and Axonal Injury in a Mouse Model of Controlled Cortical Impact

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