Biology subjects

Reiter, N.

Publications and source records attributed to Reiter, N..

5 recordsLinked to original sources

bioRxiv2026

The Mechanical Fingerprint of Hippocampal Sclerosis Linking Neuronal Cell Loss and Gliosis to Tissue Stiffness

Hippocampal sclerosis (HS) is the most common pathology in drug-resistant temporal lobe epilepsy (TLE). However, clinical diagnosis, prevalent epileptogenicity, and drug drug-resistance in individuals with HS remain an ongoing challenge demanding multidisciplinary research efforts. In this study, we examined the mechanical properties of neurosurgically en bloc resected HS specimens (n=8) ex vivo under compression, tension, and torsional shear. We fitted a two-term Ogden hyperelastic model to the measured mechanical responses to quantify nonlinear mechanical tissue properties. The resulting parameters revealed higher strain stiffening under compression in HS compared to hippocampus obtained post mortem (n=7). The distinction was most noticeable in the large-strain regime, which has important implications for using mechanical tissue properties as valuable diagnostic biomarker. Furthermore, we correlated the tissue microstructure with mechanical parameters. We trained a deep-learning histopathology classifier to detect and classify neurons and glial cells from hematoxylin-stained whole slide images (WSI). We identified a strong association between the small-strain stiffness (shear modulus {micro}) and the overall cell density as well as the glial cell density. The negative relationship between the neuron-to-glia ratio and shear modulus is consistent with the hypothesis that neuronal cell loss and gliosis drives tissue stiffening, respectively. Magnetic resonance imaging (MRI) analysis of the specimens confirmed the previously reported negative association between MRI-derived fractional anisotropy and shear modulus {micro}. Taken together, our study establishes a direct link between tissue mechanics and microstructure, suggesting nonlinear continuum mechanics models as promising new tools for clinical diagnosis and novel research strategies.

bioengineering↗

bioRxiv2026

Fractional Anisotropy as a Surrogate Marker of Brain Mechanics

Understanding the mechanical properties of brain tissue may provide crucial insights into brain development, injury, disease and surgical planning. Conventionally, these properties are measured ex vivo or in vivo during surgical procedures, while non-invasive in vivo alternatives are sparse. This study investigates whether fractional anisotropy (FA) derived from diffusion-weighted magnetic resonance imaging can serve as a surrogate marker for brain tissue stiffness in healthy human brains. MRI data were collected from three body donor brains, 28 healthy adults, and a publicly available independent dataset of 26 adults. FA values were compared with mechanical properties from ex vivo mechanical testing of brain tissue. Statistical analysis revealed a strong negative correlation between FA and the mechanical response for small strains expressed as shear modulus of a one-term hyperelastic Ogden model, indicating that higher FA values are associated with lower tissue stiffness. The nonlinearity parameter alpha exhibited a qualitatively similar, but considerably weaker correlation with FA. These findings were consistent across datasets. The findings suggest that FA can be a robust, non-invasive marker for estimating mechanical properties of brain tissue, with potential applications in clinical diagnosis and computational modeling of brain mechanics and the study of brain development. Further research is needed to clarify the relationship in lesional tissues and to optimize clinical utility.

neuroscience↗

bioRxiv2025

SCAMP3 is essential for proper formation and function of neutrophil granules

Host defense functions of neutrophils during infection critically depend on microbicidal and proteolytic proteins stored in primary, secondary and tertiary granules that are released into the phagosome or into the extracellular space upon degranulation. Granules are generated during granulopoiesis and impaired granule production or granule protein sorting has been linked to inefficient pathogen clearance resulting in recurrent bacterial and fungal infections. Here, we studied the role of the membrane protein secretory carrier associated membrane protein 3 (SCAMP3) for neutrophil defense functions. We generated Scamp3 knockout (KO) Hoxb8 cells and found that killing of Escherichia coli by Scamp3 KO Hoxb8 cell-derived neutrophils (dHoxb8 cells) was compromised as compared to control dHoxb8 cells in vitro. Mass spectrometric and Western blot analyses revealed a significant reduction of primary, secondary, and tertiary granule proteins in the genetic absence of Scamp3, resulting in a reduced overall granularity of these cells. Accordingly, degranulation was reduced in Scamp3 KO dHoxb8 cells compared to control dHoxb8 cells. Similarly, SCAMP3 deficiency in zebrafish resulted in reduced neutrophil granularity in comparison to wild-type animals. However, neutrophil migration towards sites of E. coli infection was unaffected in scamp3 KO zebrafish larvae. In summary, SCAMP3 represents an important novel player in granule equipment and degranulation, with key functions in neutrophil defense mechanisms during host-pathogen interactions in vitro. Brief summary sentence: The membrane protein secretory carrier associated membrane protein 3 (SCAMP3) is essential for proper protein equipment of neutrophil granules and Scamp3-deficient neutrophils have an impaired bacterial killing capacity in vitro.

physiology↗

bioRxiv2025

Mechanical impact on neural stem cell lineage decisions in human brain organoids

During neurodevelopment neural stem cells give rise to a spatially patterned tissue in which a regionally differentially regulated balance between proliferation and differentiation produces the fine-tuned number of neurons and macroglia necessary for a functional central nervous system. The cells driving these highly intricated developmental processes of patterning, growth and differentiation are constantly exposed to a mechanical environment that is however variable between different brain regions and along differentiation trajectories. Here we demonstrate that both, acute mechanical manipulations as well as a persistent change in the mechanical environment provided to human brain organoids, instruct neural stem cell lineage decisions. Furthermore, we dissect the underlying changes in the molecular program of organoid-resident cells by bulk- and single cell RNA-sequencing and reveal that mechanical manipulations impact on molecular programs governing early patterning events as well as cell-type specifically alter cellular metabolism. Thus, our results unravel a regulatory network linking mechanics and neural stem cell lineage decisions.

neuroscience↗

bioRxiv2022

Inverse identification of region-specific hyperelastic material parameters for human brain tissue

The identification of material parameters accurately describing the region-dependent mechanical behavior of human brain tissue is crucial for computational models used to assist, e.g., the development of safety equipment like helmets or the planning and execution of brain surgery. While the division of the human brain into different anatomical regions is well established, knowledge about regions with distinct mechanical properties remains limited. Here, we establish an inverse parameter identification scheme using a hyperelastic Ogden model and experimental data from multi-modal testing of tissue from 19 anatomical human brain regions to identify mechanically distinct regions and provide the corresponding material parameters. We assign the 19 anatomical regions to nine governing regions based on similar parameters and microstructures. Statistical analyses confirm differences between the regions and indicate that at least the corpus callosum and the corona radiata should be assigned different material parameters in computational models of the human brain. We provide a total of four parameter sets based on the two initial Poissons ratios of 0.45 and 0.49 as well as the pre- and unconditioned experimental responses, respectively. Our results highlight the close interrelation between the Poissons ratio and the remaining model parameters. The identified parameters will contribute to more precise computational models enabling spatially resolved predictions of the stress and strain states in human brains under complex mechanical loading conditions.

bioengineering↗