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Mechanisms of mechanical load transfer through brain tissue.

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

SUBMITTER: Reiter N

PROVIDER: S-EPMC10227083 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Mechanisms of mechanical load transfer through brain tissue.

Reiter Nina N Paulsen Friedrich F Budday Silvia S

Scientific reports 20230529 1

Brain injuries are often characterized by diffusely distributed axonal and vascular damage invisible to medical imaging techniques. The spatial distribution of mechanical stresses and strains plays an important role, but is not sufficient to explain the diffuse distribution of brain lesions. It remains unclear how forces are transferred from the organ to the cell scale and why some cells are damaged while neighboring cells remain unaffected. To address this knowledge gap, we subjected histologic ...[more]

PMID: 37248296

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Project description:AimsCardiac remodelling is the process by which the heart adapts to its environment. Mechanical load is a major driver of remodelling. Cardiac tissue culture has been frequently employed for in vitro studies of load-induced remodelling; however, current in vitro protocols (e.g. cyclic stretch, isometric load, and auxotonic load) are oversimplified and do not accurately capture the dynamic sequence of mechanical conformational changes experienced by the heart in vivo. This limits translational scope and relevance of findings.Methods and resultsWe developed a novel methodology to study chronic load in vitro. We first developed a bioreactor that can recreate the electromechanical events of in vivo pressure-volume loops as in vitro force-length loops. We then used the bioreactor to culture rat living myocardial slices (LMS) for 3 days. The bioreactor operated based on a 3-Element Windkessel circulatory model enabling tissue mechanical loading based on physiologically relevant parameters of afterload and preload. LMS were continuously stretched/relaxed during culture simulating conditions of physiological load (normal preload and afterload), pressure-overload (normal preload and high afterload), or volume-overload (high preload & normal afterload). At the end of culture, functional, structural, and molecular assays were performed to determine load-induced remodelling. Both pressure- and volume-overloaded LMS showed significantly decreased contractility that was more pronounced in the latter compared with physiological load (P < 0.0001). Overloaded groups also showed cardiomyocyte hypertrophy; RNAseq identified shared and unique genes expressed in each overload group. The PI3K-Akt pathway was dysregulated in volume-overload while inflammatory pathways were mostly associated with remodelling in pressure-overloaded LMS.ConclusionWe have developed a proof-of-concept platform and methodology to recreate remodelling under pathophysiological load in vitro. We show that LMS cultured in our bioreactor remodel as a function of the type of mechanical load applied to them.

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Mechanisms of mechanical load transfer through brain tissue.

Publications

Mechanisms of mechanical load transfer through brain tissue.

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