Biomechanical analysis of fluid percussion model of brain injury

Mao, Haojie; Lu, Lihong; Bian, Kewei; Clausen, Fredrik; Colgan, Niall; Gilchrist, Michael D.

doi:10.1016/j.jbiomech.2018.07.004

“…Recent in silico modeling of lFPI included a three-layer hexahedral, element-based skull module with varying Young modulus for each layer. 72 The model used a uniformly thick skull and predicted significant strain in regions surrounding the initial injury site that dissipate through the brain, in contrast to our neuropathology results and those of others (Table 1).…”

Section: Discussioncontrasting

confidence: 70%

Spatial Distribution of Neuropathology and Neuroinflammation Elucidate the Biomechanics of Fluid Percussion Injury

Beitchman

¹

,

Lifshitz

²

,

Harris

³

et al. 2021

Neurotrauma Reports

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Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. We hypothesized that local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology. We demonstrated local thickening of the skull at the temporal ridges using contour analysis on magnetic resonance imaging. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, and 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge before injury reduced injury-induced inflammation in the sensorimotor cortex. These data build evidence for temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.

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“…In laboratory closed-head impact tests, no matter where the animal heads were hit, the induced linear and rotational kinematics were the culprits that induced brain responses and led to brain damage, especially for mild TBI impacts for which skull deformation is limited. Meanwhile, open-skull laboratory neurotrauma loadings such as CCI and FPI are still widely used, for which part of the skull was removed and mouse cortical brain could experience strains up to 0.3 and higher in CCI (6) and around 0.10 in FPI (7). The focus on rotational kinematics in this study was consistent with mouse model such as CHIMERA ( 9) and swine models, both focusing on inducing head rotations (51,52).…”

Section: Discussionsupporting

confidence: 54%

“…Openskull TBI using the cortical impactor has been popular as it allows direct loading to the brain tissue and induces high brain strain above 0.30 to the underlying cortical layers (6). Open-skull TBI using the FPI also induces high strain up to ~ 0.1 and high pressure of approximately 180 kPa (7). Despite the greater convenience of open skull TBI, closed-head TBI is considered more clinically relevant because it does not require a craniotomy (8) and real-world mTBI/concussions happen with closed-skull conditions.…”

Section: Introductionmentioning

confidence: 99%

Developing Brain-Strain-Based Scaling to Inform the Clinical Relevance of Mouse Models of Concussion Induced by Rotation

Liu

¹

,

Lu

²

,

Bian

³

et al. 2021

Preprint

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Background Laboratory animal experiments are an invaluable tool for studying mild traumatic brain injury (mTBI)/concussion. Among them, rodent neurotrauma experiments have been most widely used, as transgenic and gene targeting technologies in mice allow us to test the roles of different genes in recovery from brain injury. Furthermore, the clinical relevance of rodent concussion studies can be improved by using these technologies to study concussions in animals that carry the human versions of genes known to play a role in neurological disease. However, delivering concussion injuries to the mice that are relevant to real-world human head impacts is challenging, as the mouse and human heads are dramatically different in shape and size. In the vast majority of mouse concussion experiments, the pathological and behavioral consequences of the injuries are evaluated without considering whether the injury model produces brain stretches (maximum principal strains) of the same magnitude as those experienced by human brains undergoing similar impacts. Methods We conducted a total of 201 computational simulations to understand both human and mouse brain strains that are directly linked to neuronal damage during closed-head concussive impacts. To represent real-world human head impacts we simulated mouse head impacts with durations of 1.5 ms (Type 1 scaling), followed by simulations with durations between 1 and 2 ms (Type 2), and finally, simulations with durations from 0.75 to 4.5 ms (Type 3) to develop scaling between human and mouse, as well as to reveal the predicted effects of small and large changes in impact durations on brain strain. Results Guided by these simulations we calculated that peak rotational velocities in mice could be achieved by scaling human peak rotational velocities with factors of 5.8, 4.6, and 6.8, for flexion/extension, lateral bending, and axial rotation, respectively, to reach equal brain strains between human and mouse. The effects of impact durations on scaling were also calculated and longer-duration mouse head impacts needed larger scaling factors to reach equal strain. Conclusions The scaling method will help us to create brain injury in the mouse with brain strain loading equivalent to those experienced in real-world human head impacts.

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“…For this model, it appears that the applied mechanical force increased strain and stress on neuronal tissue, with the likely consequence of tissue forced against different parts of the skull. Recent in silico modeling of lFPI included a 3-layer hexahedral, element-based skull module with varying Young modulus for each layer [65]. The uniformly thick skull appeared not to influence the results, which showed local forces at the site of injury and secondarily at the ventral aspect of the brain, as proposed here.…”

Section: Discussionmentioning

confidence: 66%

Spatial distribution of neuropathology and neuroinflammation elucidate the biomechanics of fluid percussion injury

Beitchman¹,

Lifshitz

²

,

Harris³

et al. 2020

Preprint

0

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Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. Finite element biomechanical models of diffuse brain injury predict regions of maximum stress and strain. However, the application of a skull with uniform thickness may mask the pathophysiology due to varying thickness of human and animal skulls. Force applied to the intact skull would diffuse the forces, whereas forces applied through an open skull are distributed along paths of least resistance within and then exiting the skull. We hypothesized that the local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology in underlying cortical tissue. We demonstrated local thickening of the skull at the temporal ridges using contour analysis of coronal skull sections and oblique sectioning on MRI. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge due to the material properties of the skull based on thickness, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge prior to injury reduced the injury-induced inflammation in sensorimotor cortex. These data build evidence for the temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.HighlightsThe temporal ridge is 75% thicker than the adjacent skull of the rodentExperimental diffuse TBI neuropathology occurs beneath the length of the temporal ridgeNeuropathology encompasses sensorimotor cortex, somatosensory thalamus, and dorsolateral hippocampusProposed mechanism of biomechanical injury forces include the temporal ridge

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Biomechanical analysis of fluid percussion model of brain injury

Cited by 15 publications

References 22 publications

Spatial Distribution of Neuropathology and Neuroinflammation Elucidate the Biomechanics of Fluid Percussion Injury

Spatial Distribution of Neuropathology and Neuroinflammation Elucidate the Biomechanics of Fluid Percussion Injury

Developing Brain-Strain-Based Scaling to Inform the Clinical Relevance of Mouse Models of Concussion Induced by Rotation

Spatial distribution of neuropathology and neuroinflammation elucidate the biomechanics of fluid percussion injury

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