Brain maturation is associated with increasing tissue stiffness and decreasing tissue fluidity

Guo, Jing; Bertalan, Gergely; Meierhofer, David; Klein, Charlotte; Schreyer, Stefanie; Steiner, Barbara; Wang, Shuangqing; Silva, Rafaela Vieira; Infante-Duarte, Carmen; Koch, Stefan P.; Boehm‐Sturm, Philipp; Braun, Jürgen; Sack, Ingolf

doi:10.1016/j.actbio.2019.08.036

Cited by 63 publications

(49 citation statements)

References 46 publications

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“…Future mechanobiology experiments in the CNS should aim to elucidate the role of astrocytes and other glial cells in communicating mechanobiological information to local neural networks (Blumenthal, Hermanson, Heimrich, & Shastri, 2014). The studies described above provide some mechanistic insight into how cell and tissue mechanics can influence brain development (Barnes, Przybyla, & Weaver, 2017;Farge, 2011;Guo et al, 2019;Heisenberg & Bellaïche, 2013;Koser et al, 2016;Wozniak & Chen, 2009). In contrast, our current understanding of how the brain's mechanical properties change in old age or in response to neuropathologies like Alzheimer's disease is somewhat limited (Wu, Fannin, Rice, Wang, & Blough, 2011).…”

Section: Mechanotransduction and Electrophysiologymentioning

confidence: 99%

Mechanobiology of the brain in ageing and Alzheimer's disease

Hall

Moeendarbary

Sheridan

2020

Eur J of Neuroscience

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Section: Mechanotransduction and Electrophysiologymentioning

confidence: 99%

Mechanobiology of the brain in ageing and Alzheimer's disease

Hall

Moeendarbary

Sheridan

2020

Eur J of Neuroscience

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“…Children have larger head-to-body ratios and less neck strength, which can influence how mechanical injury forces impact the brain. Additionally, incomplete myelination leads to differences in tissue viscosity which can influence response to injury (Guo et al , 2019) . TBI can lead to cognitive impairment in all patients, but in children this disruption can become more apparent over time, as children fail to meet the increasing demands of educational activities (Ewing-Cobbs et al , 2004;Anderson et al , 2005;Babikian and Asarnow, 2009;Wells et al , 2009;Ryan et al , 2015) .…”

Section: Introductionmentioning

confidence: 99%

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Dennis

Caeyenberghs

Hoskinson

et al. 2020

Preprint

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Annually, approximately 3 million children around the world experience traumatic brain injuries (TBIs), of which up to 20% are characterized as moderate to severe (msTBI) and/or have abnormal imaging findings. Affected children are vulnerable to long-term cognitive and behavioral dysfunction, as injury can disrupt or alter ongoing brain maturation. Post-injury outcomes are highly variable, and there is only limited understanding of how inter-individual differences in outcomes arise. Small sample sizes have also complicated efforts to better understand factors influencing the impact of TBI on the developing brain. White matter (WM) disruption is a critical aspect of TBI neuropathology and diffusion MRI (dMRI) is particularly sensitive to microstructural abnormalities. Here we present the results of a coordinated analysis of dMRI data across ten cohorts from three countries. We had three primary aims: (1) to characterize the nature and extent of WM disruption across key post-injury intervals (acute/subacute - within 2 months, post-acute - 2-6 months, chronic - 6+ months); (2) evaluate the impact of age and sex on WM in the context of injury; and (3) to examine associations between WM and neurobehavioral outcomes. Based on data from 507 children and adolescents (244 with complicated mild to severe TBI and 263 control children), we report widespread WM disruption across all post-injury intervals. As expected, injury severity was a significant contributor to the pattern and extent of WM degradation, but explained less variance in dMRI measures with increasing time since injury, supporting other research indicating that other factors contribute increasingly to outcomes over time. The corpus callosum appears to be particularly vulnerable to injury, an effect that persists years post-TBI. We also report sex differences in the effect of TBI on the uncinate fasciculus (UNC), a structure with a key role in emotion regulation. Females with a TBI had significantly lower fractional anisotropy (FA) in the UNC than those with no TBI, and this phenomenon was further associated with more frequent parent-reported behavioral problems as measured by the Child Behavior Checklist (CBCL). These effects were not detected in males. With future harmonization of imaging and neurocognitive data, more complex modeling of factors influencing outcomes will be possible and help to identify clinically-meaningful patient subtypes.

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“…Frozen whole-brain (350-450 mg, 4 random mice/genotype/diet) was prepared and homogenized. 18-55 mg were used for lysates, 30 μg digested and 1 μg was analyzed using nano-LC-MS/MS as described [ 52 , 53 ]. Data were processed with MaxQuant (V1.6.0.1) [ 54 ] and searched against mouse UniProtKB with 21,074 entries, released 12/2018.…”

Section: Methodsmentioning

confidence: 99%

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

Schreyer

Berndt

Eckstein

et al. 2021

Aging

Self Cite

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Alzheimer’s disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by 1 H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.

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Brain maturation is associated with increasing tissue stiffness and decreasing tissue fluidity

Cited by 63 publications

References 46 publications

Mechanobiology of the brain in ageing and Alzheimer's disease

Mechanobiology of the brain in ageing and Alzheimer's disease

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis

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