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1. Implant Design and Cervical Spinal Biomechanics and Neurorehabilitation: A Finite Element Investigation

   https://doi.org/10.1093/milmed/usae279  

   Bahreinizad, Hossein ; Chowdhury, Suman_K ( August 2024 , Military Medicine)

   The cervical spine, pivotal for mobility and overall body function, can be affected by cervical spondylosis, a major contributor to neural disorders. Prevalent in both general and military populations, especially among pilots, cervical spondylosis induces pain and limits spinal capabilities. Anterior Cervical Discectomy and Fusion (ACDF) surgery, proposed by Cloward in the 1950s, is a promising solution for restoring natural cervical curvature. The study objective was to investigate the impacts of ACDF implant design on postsurgical cervical biomechanics and neurorehabilitation outcomes by utilizing a biofield head-neck finite element (FE) platform that can facilitate scenario-specific perturbations of neck muscle activations. This study addresses the critical need to enhance computational models, specifically FE modeling, for ACDF implant design.

   We utilized a validated head-neck FE model to investigate spine–implant biomechanical interactions. An S-shaped dynamic cage incorporating titanium (Ti) and polyetheretherketone (PEEK) materials was modeled at the C4/C5 level. The loading conditions were carefully designed to mimic helmet-to-helmet impact in American football, providing a realistic and challenging scenario. The analysis included intervertebral joint motion, disk pressure, and implant von Mises stress.

   The PEEK implant demonstrated an increased motion in flexion and lateral bending at the contiguous spinal (C4/C5) level. In flexion, the Ti implant showed a modest 5% difference under 0% activation conditions, while PEEK exhibited a more substantial 14% difference. In bending, PEEK showed a 24% difference under 0% activation conditions, contrasting with Ti’s 17%. The inclusion of the head resulted in an average increase of 18% in neck angle and 14% in C4/C5 angle. Disk pressure was influenced by implant material, muscle activation level, and the presence of the head. Polyetheretherketone exhibited lower stress values at all intervertebral disc levels, with a significant effect at the C6/C7 levels. Muscle activation level significantly influenced disk stress at all levels, with higher activation yielding higher stress. Titanium implant consistently showed higher disk stress values than PEEK, with an orders-of-magnitude difference in von Mises stress. Excluding the head significantly affected disk and implant stress, emphasizing its importance in accurate implant performance simulation.

   This study emphasized the use of a biofidelic head-neck model to assess ACDF implant designs. Our results indicated that including neck muscles and head structures improves biomechanical outcome measures. Furthermore, unlike Ti implants, our findings showed that PEEK implants maintain neck motion at the affected level and reduce disk stresses. Practitioners can use this information to enhance postsurgery outcomes and reduce the likelihood of secondary surgeries. Therefore, this study makes an important contribution to computational biomechanics and implant design domains by advancing computational modeling and theoretical knowledge on ACDF–spine interaction dynamics.

    

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2. GdDO3NI Enhanced Magnetic Resonance Imaging Allows Imaging of Hypoxia After Brain Injury

   https://doi.org/10.1002/jmri.27912  

   Moghadas, Babak ; Bharadwaj, Vimala N. ; Tobey, John P. ; Tian, Yanqing ; Stabenfeldt, Sarah E. ; Kodibagkar, Vikram D. ( September 2021 , Journal of Magnetic Resonance Imaging)

   Brain tissue hypoxia is a common consequence of traumatic brain injury (TBI) due to the rupture of blood vessels during impact and it correlates with poor outcome. The current magnetic resonance imaging (MRI) techniques are unable to provide a direct map of tissue hypoxia.

   To investigate whether GdDO3NI, a nitroimidazole‐based T₁MRI contrast agent allows imaging hypoxia in the injured brain after experimental TBI.

   Prospective.

   TBI‐induced mice (controlled cortical impact model) were intravenously injected with either conventional T₁agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n = 5 for each cohort) along with pimonidazole (60 mg/kg) at 1 hour postinjury and imaged for 3 hours following which they were euthanized.

   7 T/T₂‐weighted spin echo and T₁‐weighted gradient echo.

   Injured animals were imaged with T₂‐weighted spin‐echo sequence to estimate the extent of the injury. The mice were then imaged precontrast and postcontrast using a T₁‐weighted gradient‐echo sequence for 3 hours postcontrast. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post‐imaging for immunohistochemical analysis.

   One‐way analysis of variance and two‐samplet‐tests were performed with aP < 0.05 was considered statistically significant.

   GdDO3NI retention in the injury region at 2.5–3 hours post‐injection was significantly higher compared to gadoteridol (mean retention fraction 63.95% ± 27.43% vs. 20.68% ± 7.43% for gadoteridol at 3 hours) while it rapidly cleared out of the muscle region. Pimonidazole staining confirmed the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort showed good agreement with MRI contrast enhancement.

   GdDO3NI was successfully shown to visualize hypoxia in the brain post‐TBI using T₁‐weighted MRI at 2.5–3 hours postcontrast.

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3. Noninvasive and reliable automated detection of spreading depolarization in severe traumatic brain injury using scalp EEG

   https://doi.org/10.1038/s43856-023-00344-3  

   Chamanzar, Alireza ; Elmer, Jonathan ; Shutter, Lori ; Hartings, Jed ; Grover, Pulkit ( December 2023 , Communications Medicine)

   Spreading depolarizations (SDs) are a biomarker and a potentially treatable mechanism of worsening brain injury after traumatic brain injury (TBI). Noninvasive detection of SDs could transform critical care for brain injury patients but has remained elusive. Current methods to detect SDs are based on invasive intracranial recordings with limited spatial coverage. In this study, we establish the feasibility of automated SD detection through noninvasive scalp electroencephalography (EEG) for patients with severe TBI.

   Building on our recent WAVEFRONT algorithm, we designed an automated SD detection method. This algorithm, with learnable parameters and improved velocity estimation, extracts and tracks propagating power depressions using low-density EEG. The dataset for testing our algorithm contains 700 total SDs in 12 severe TBI patients who underwent decompressive hemicraniectomy (DHC), labeled using ground-truth intracranial EEG recordings. We utilize simultaneously recorded, continuous, low-density (19 electrodes) scalp EEG signals, to quantify the detection accuracy of WAVEFRONT in terms of true positive rate (TPR), false positive rate (FPR), as well as the accuracy of estimating SD frequency.

   WAVEFRONT achieves the best average validation accuracy using Delta band EEG: 74% TPR with less than 1.5% FPR. Further, preliminary evidence suggests WAVEFRONT can estimate how frequently SDs may occur.

   We establish the feasibility, and quantify the performance, of noninvasive SD detection after severe TBI using an automated algorithm. The algorithm, WAVEFRONT, can also potentially be used for diagnosis, monitoring, and tailoring treatments for worsening brain injury. Extension of these results to patients with intact skulls requires further study.

    

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4. Blueberry Supplementation Mitigates Altered Brain Plasticity and Behavior after Traumatic Brain Injury in Rats

   https://doi.org/10.1002/mnfr.201801055  

   Krishna, Gokul ; Ying, Zhe ; Gomez‐Pinilla, Fernando ( May 2019 , Molecular Nutrition & Food Research)

   Traumatic brain injury (TBI) compromises neuronal function required for hippocampal synaptic plasticity and cognitive function. Despite the high consumption of blueberries, information about its effects on brain plasticity and function under conditions of brain trauma is limited. The efficacy of dietary blueberry (BB) supplementation to mitigate the effects of TBI on plasticity markers and associated behavioral function in a rodent model of concussive injury are assessed.

   Rats were maintained on a diet supplemented with blueberry (BB, 5% w/w) for 2 weeks after TBI. It is found that BB supplementation mitigated a loss of spatial learning and memory performance after TBI, and reduced the effects of TBI on anxiety‐like behavior. BB supplementation prevents a reduction of molecules associated with the brain‐derived neurotrophic factor (BDNF) system action on learning and memory such as cyclic‐AMP response element binding factor (CREB), calcium/calmodulin‐dependent protein kinase II (CaMKII). In addition, BB supplementation reverses an increase of the lipid peroxidation byproduct 4‐hydroxy‐nonenal (4‐HNE) after TBI. Importantly, synaptic and neuronal signaling regulators change in proportion with the memory performance, suggesting an association between plasticity markers and behavior.

   Data herein indicate that BB supplementation has a beneficial effect in mitigating the acute aspects of the TBI pathology.

    

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5. Brain Trauma Disrupts Hepatic Lipid Metabolism: Blame It on Fructose?

   https://doi.org/10.1002/mnfr.201801054  

   Rege, Shraddha D. ; Royes, Luiz ; Tsai, Brandon ; Zhang, Guanglin ; Yang, Xia ; Gomez‐Pinilla, Fernando ( June 2019 , Molecular Nutrition & Food Research)

   The action of brain disorders on peripheral metabolism is poorly understood. The impact of traumatic brain injury (TBI) on peripheral organ function and how TBI effects can be influenced by the metabolic perturbation elicited by fructose ingestion are studied.

   It is found that TBI affects glucose metabolism and signaling proteins for insulin and growth hormone in the liver; these effects are exacerbated by fructose ingestion. Fructose, principally metabolized in the liver, potentiates the action of TBI on hepatic lipid droplet accumulation. Studies in isolated cultured hepatocytes identify GH and fructose as factors for the synthesis of lipids. The liver has a major role in the synthesis of lipids used for brain function and repair. TBI results in differentially expressed genes in the hypothalamus, primarily associated with lipid metabolism, providing cues to understand central control of peripheral alterations. Fructose‐fed TBI animals have elevated levels of markers of inflammation, lipid peroxidation, and cell energy metabolism, suggesting the pro‐inflammatory impact of TBI and fructose in the liver.

   Results reveal the impact of TBI on systemic metabolism and the aggravating action of fructose. The hypothalamic‐pituitary‐growth axis seems to play a major role in the regulation of the peripheral TBI pathology.

    

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