Journal of neurotrauma
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Journal of neurotrauma · Aug 2023
Investigating the Effect of Brain Size on Deformation Magnitude using Subject-Specific Finite Element Models.
Abstract In the last decade, computational models of the brain have become the gold standard tool for investigating traumatic brain injury (TBI) mechanisms and developing novel protective equipment and other safety countermeasures. However, most studies utilizing finite element (FE) models of the brain have been conducted using models developed to represent the average neuroanatomy of a target demographic, such as the 50th percentile male. Although this is an efficient strategy, it neglects normal anatomical variations present within the population and their contributions on the brain's deformation response. ⋯ Both techniques indicated a strong linear relationship between ICV and MPS-95, with MPS-95 varying by approximately 5% between the smallest and largest brains. This difference represented up to 40% of the mean strain across all subjects. This study represents a comprehensive assessment of the relationships between brain anatomy and deformation, which is crucial for the development of personalized protective equipment, identifying individuals at higher risk of injury, and using computational models to aid clinical diagnostics of TBI.
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Journal of neurotrauma · Aug 2023
TRPM4 drives cerebral edema by switching to alternative splicing isoform after experimental traumatic brain injury.
Traumatic brain injury (TBI) affects persons of all ages and is recognized as a major cause of death and disability worldwide; it also brings heavy life burden to patients and their families. The treatment of those with secondary injury after TBI is still scarce, however. Alternative splicing (AS) is a crucial post-transcriptional regulatory mechanism associated with various physiological processes, while the contribution of AS in treatment after TBI is poorly illuminated. ⋯ Thus alternative splicing of Trpm4 becomes a noteworthy mechanism of potential influence on edema. In summary, alternative splicing of Trpm4 may drive cerebral edema after TBI. Trpm4 is a potential therapeutic targeting cerebral edema in patients with TBI.
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Journal of neurotrauma · Aug 2023
Optimizing choice and timing of behavioral outcome tests following repetitive mild traumatic brain injury: A machine learning-based approach on multiple preclinical experiments.
Repetitive mild traumatic brain injury (rmTBI) is a potentially debilitating condition with long-term sequelae. Animal models are used to study rmTBI in a controlled environment, but there is currently no established standard battery of behavioral tests used. Primarily, we aimed to identify the best combination and timing of behavioral tests to distinguish injured from uninjured animals in rmTBI studies, and secondarily, to determine whether combinations of independent experiments have better behavioral outcome prediction accuracy than individual experiments. ⋯ Combinations of open field tests and elevated plus mazes also performed well (AUC = 0.92), as did the forced swim test alone (AUC = 0.90). In summary, multiple heterogeneous experiments tended to predict outcome better than individual experiments, and MWM 3-4 months after injury was the optimal test, also several combinations also performed well. In order to design future pre-clinical rmTBI trials, we have included an interactive application available online utilizing the data from the study via the Supplementary URL.
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Journal of neurotrauma · Jul 2023
Cerebrospinal fluid levels of lysophosphatidic acids can provide suitable biomarkers of blast-induced traumatic brain injury.
Blast-induced traumatic brain injury (bTBI) has been identified as the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom. Although the incidence of bTBI increased significantly after the introduction of improvised explosive devices, the mechanism of the injury is still uncertain, which is negatively impacting the development of suitable countermeasures. Identification of suitable biomarkers that could aid in the proper diagnosis of and prognosis for both acute and chronic bTBI is essential since bTBI frequently is occult and may not be associated with overtly detectable injuries to the head. ⋯ In the plasma, several LPA species increased acutely, returned to normal levels by 24 h, and were significantly decreased at 1 year post-blast overpressure exposures. These decreases in LPA species in the plasma were associated with decreased levels of lysophosphatidyl choline, suggesting a defective upstream biosynthetic pathway of LPAs in the plasma. Notably, the changes in LPA levels in the CSF (but not plasma) negatively correlated with neurobehavioral functions in these rats, suggesting that CSF levels of LPAs may provide a suitable biomarker of bTBI that reflects severity of injury.
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Journal of neurotrauma · Jul 2023
ReviewPutting the mind to rest: a historical foundation for rest as a treatment for traumatic brain injury.
Rest after traumatic brain injury (TBI) has been a part of clinical practice for more than a century but the use of rest as a treatment has ancient roots. In contemporary practice, rest recommendations have been significantly reduced but are still present. This advice to brain injured patients, on the face of it makes some logical sense but was not historically anchored in either theory or empirical data. ⋯ The goals and theoretical explanations for this approach have evolved and in modern conception include avoiding reinjury and reducing the metabolic demands on injured tissue. Moreover, as cellular and molecular understanding of the physiology of TBI developed, scientists and clinicians sometimes retroactively cited these new data in support of rest recommendations. Here, we trace the history of this approach and how it has been shaped by new understanding of the underlying pathology associated with brain injury.