Multimodal Neuromonitoring and Neurocritical Care in Swine to Enhance Translational Relevance in Brain Trauma Research DOI Creative Commons
John C. O’Donnell, Kevin D. Browne, Svetlana Kvint

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1336 - 1336

Published: April 30, 2023

Neurocritical care significantly impacts outcomes after moderate-to-severe acquired brain injury, but it is rarely applied in preclinical studies. We created a comprehensive neurointensive unit (neuroICU) for use swine to account the influence of neurocritical care, collect clinically relevant monitoring data, and create paradigm that capable validating therapeutics/diagnostics unique space. Our multidisciplinary team neuroscientists, neurointensivists, veterinarians adapted/optimized clinical neuroICU (e.g., multimodal neuromonitoring) critical pathways managing cerebral perfusion pressure with sedation, ventilation, hypertonic saline) swine. Moreover, this enabled first demonstration an extended study period traumatic injury coma beyond 8 h. There are many similarities humans make ideal model species studies, including large mass, gyrencephalic cortex, high white matter volume, topography basal cisterns, amongst other factors. Here we describe techniques developed medical management following subarachnoid hemorrhage coma. Incorporating studies will reduce translational gap therapeutics diagnostics specifically tailored injury.

Language: Английский

Traumatic Brain Injury: A Comprehensive Review of Biomechanics and Molecular Pathophysiology DOI

Taylor Orr,

Emal Lesha, Alexandra H. Kramer

et al.

World Neurosurgery, Journal Year: 2024, Volume and Issue: 185, P. 74 - 88

Published: Jan. 23, 2024

Language: Английский

Citations

15

WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury DOI Creative Commons
Yuhua Chen,

Tianlin Long,

Junhui Chen

et al.

International Journal of Surgery, Journal Year: 2024, Volume and Issue: 110(9), P. 5396 - 5408

Published: June 14, 2024

Background Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, authors explored epigenetic methylation RNA-mediated NLRP3 inflammasome activation Methods Neurological dysfunction, histopathology, associated molecules were examined in conditional knockout (CKO) WTAP [flox/flox, Camk2a-cre] , flox/flox pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons used vitro to further explore molecular mechanisms action WTAP/YTHDF1 following neural damage. Results The found that m6A levels upregulated at early stage TBI, deletion did not affect function but promoted functional recovery Conditional suppressed neuroinflammation TBI phase: could directly act on mRNA, regulate mRNA level, promote expression neuronal injury. Further investigation YTH domain YTHDF1 bind protein expression. mutation or silencing improved injury, inhibited Caspase-1 activation, decreased IL-1β levels. This effect was mediated via suppression translation, which also reversed stimulative overexpression inflammation. Conclusions Our results indicate participates damage by translation m6A-YTHDF1-dependent manner WTAP/m6A/YTHDF1 downregulation therapeutics viable promising approach preserving can provide support targeted drug development.

Language: Английский

Citations

14

KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury DOI Creative Commons
Jesse D. Lai, Joshua Berlind, Gabriella Fricklas

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(4), P. 519 - 536.e8

Published: April 1, 2024

Language: Английский

Citations

10

Magnetic resonance elastography in a nutshell: Tomographic imaging of soft tissue viscoelasticity for detecting and staging disease with a focus on inflammation DOI Creative Commons
Tom Meyer, Johannes Castelein,

Jakob Schattenfroh

et al.

Progress in Nuclear Magnetic Resonance Spectroscopy, Journal Year: 2024, Volume and Issue: 144-145, P. 1 - 14

Published: May 29, 2024

Magnetic resonance elastography (MRE) is an emerging clinical imaging modality for characterizing the viscoelastic properties of soft biological tissues. MRE shows great promise in noninvasive diagnosis various diseases, especially those associated with tissue changes involving extracellular matrix, cell density, or fluid turnover including altered blood perfusion – all hallmarks inflammation from early events to cancer development. This review covers fundamental principles measuring viscoelasticity by MRE, which are based on stimulation and encoding shear waves their conversion into parameter maps mechanical inverse problem solutions wave equation. Technical challenges posed real-world such as viscosity, heterogeneity, anisotropy, nonlinear elastic behavior tissues discussed. Applications measurement both humans animal models presented, emphasis detection, characterization, staging diseases related cascade biomechanical property chronic liver brain. Overall, provides valuable insights biophysics imaging-based detection inflammation-associated changes.

Language: Английский

Citations

7

Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury DOI Open Access
Wojciech Czyżewski, Jakub Litak, Jan Sobstyl

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6553 - 6553

Published: June 14, 2024

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics the brain, impacting development and resolution of edema following traumatic brain injury (TBI). This review examines alterations AQP expression localization post-injury, exploring their effects on overall outcomes. We discuss underlying molecular mechanisms expression, highlighting potential therapeutic strategies to modulate function. These insights provide comprehensive understanding AQPs TBI suggest novel approaches for improving clinical outcomes through targeted interventions.

Language: Английский

Citations

6

Spectrum of Magnetic Resonance Imaging Findings in Acute Pediatric Traumatic Brain Injury - A Pictorial Essay DOI Creative Commons
Cristina-Mihaela Popescu, Virginia Marina,

Georgiana Avram

et al.

Journal of Multidisciplinary Healthcare, Journal Year: 2024, Volume and Issue: Volume 17, P. 2921 - 2934

Published: June 1, 2024

Abstract: Head trauma (HT) in pediatric patients is the number one cause of mortality and morbidity children. Although computer tomography (CT) imaging provides ample information assessing acute traumatic brain injuries (TBIs), there are instances when magnetic resonance (MRI) needed. Due to its high sensitivity diagnosing small bleeds, MRI offers a well-documented evaluation primary TBIs. Our pictorial essay aims present some latest protocols employed head review practical considerations. Injury mechanisms accidental HT, lesions' topography, hematoma signal variability over time also discussed. Acute intra- extra-axial lesions their aspect showcased using images from our hospital. This has an educational purpose. It intended guide young emergency intensive care unit doctors, neurologists, neurosurgeons TBIs on while waiting for official radiologist's report. The presentation focuses most frequent encountered trauma. Keywords: paediatric trauma, injury, diffuse axonal haemorrhagic cortical contusions, epidural haematoma

Language: Английский

Citations

5

Unraveling the Local Relation Between Tissue Composition and Human Brain Mechanics Through Machine Learning DOI Creative Commons
Kevin Linka, Nina Reiter,

Jasmin Würges

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2021, Volume and Issue: 9

Published: Aug. 17, 2021

The regional mechanical properties of brain tissue are not only key in the context injury and its vulnerability towards loads, but also affect behavior functionality cells. Due to extremely soft nature tissue, characterization is challenging. response loading depends on length time scales characterized by nonlinearity, compression-tension asymmetry, conditioning, stress relaxation. In addition, heterogeneity–both mechanics microstructure–complicates comprehensive understanding local relation underlying microstructure. Here, we combine large-strain biomechanical tests with enzyme-linked immunosorbent assays (ELISA) develop an extended type constitutive artificial neural networks (CANNs) that can account for viscoelastic effects. We show our network able describe different regions quantify relevance cellular extracellular components time-independent (nonlinearity, compression-tension-asymmetry) time-dependent (hysteresis, relaxation) mechanics, respectively. Our results suggest content matrix protein fibronectin highly relevant both quasi-elastic effects tissue. While seems be largely controlled proteins from basement membrane, have a higher response. findings advance microstructure - relations human valuable further predictive material models finite element simulations or design biomaterials engineering 3D printing applications.

Language: Английский

Citations

30

Appreciating the role of cell shape changes in the mechanobiology of epithelial tissues DOI Creative Commons
Marine Luciano, Marie Versaevel, Eléonore Vercruysse

et al.

Biophysics Reviews, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

The wide range of epithelial cell shapes reveals the complexity and diversity intracellular mechanisms that serve to construct their morphology regulate functions. Using mechanosensitive steps, cells can sense a variety different mechanochemical stimuli adapt behavior by reshaping morphology. These changes shape rely on structural reorganization in space time generates modifications tensional state activates biochemical cascades. Recent studies have started unveil how maintenance is involved mechanical homeostatic tasks sustain tissue folding, identity, self-renewal. Here, we review relevant works integrated mechanobiology elucidate some core principles may be conveyed into spatial information guide collective processes such as morphogenesis. Among many other parameters, show regulation understood result interplay between two counteracting mechanisms: actomyosin contractility intercellular adhesions, both do not act independently but are functionally operate molecular, cellular, scales. We highlight role cadherin-based adhesions force-sensing mechanotransduction, report recent developments exploit physics liquid crystals connect orientational order aggregates. Finally, emphasize further intermingling disciplines develop new assays will lead way toward unified picture contribution pathophysiological tissues.

Language: Английский

Citations

20

Mechanisms of mechanical load transfer through brain tissue DOI Creative Commons
Nina Reiter, Friedrich Paulsen, Silvia Budday

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 29, 2023

Abstract Brain injuries are often characterized by diffusely distributed axonal and vascular damage invisible to medical imaging techniques. The spatial distribution of mechanical stresses strains plays an important role, but is not sufficient explain the diffuse brain lesions. It remains unclear how forces transferred from organ cell scale why some cells damaged while neighboring remain unaffected. To address this knowledge gap, we subjected histologically stained fresh human porcine tissue specimens compressive loading simultaneously tracked blood vessel displacements. Our experiments reveal different mechanisms load transfer or single cells, axons, vessels. results show that displacement fields inhomogeneous at interface between gray white matter in vicinity vessels—locally inducing significant deformations individual cells. These insights have implications better understand injury highlight importance vessels for local deformation brain’s cellular structure during loading.

Language: Английский

Citations

12

A narrative review of the effects of dexamethasone on traumatic brain injury in clinical and animal studies: focusing on inflammation DOI

Afsaneh Soltani,

Uliana Y. Chugaeva,

Montather F. Ramadan

et al.

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(6), P. 2955 - 2971

Published: Oct. 16, 2023

Language: Английский

Citations

11