Biology subjects

Sheng, H.

Publications and source records attributed to Sheng, H..

4 recordsLinked to original sources

bioRxiv2019

Ischemic Stroke Reduces Bone Perfusion and Alters Osteovascular Structure

RationaleStroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown.\n\nObjectiveTo characterize changes to osteovascular function, structure, and composition following mild-to-moderate-severity ischemic stroke in mice, both with and without exercise therapy.\n\nMethods and ResultsTwelve-week-old male mice (n=27) received either a stroke (middle cerebral artery occlusion) or sham procedure, followed by four weeks of daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis, was reduced by stroke for two weeks. In the second week of recovery, exercise nearly restored perfusion to sham levels, and perfusion tended to be lower in the stroke-affected limb. At the conclusion of the study, osteovascular structure was assessed with contrast-enhanced computed tomography in the distal femoral metaphysis. Stroke significantly increased osteovascular volume and branching but reduced the relative number of blood vessels close to bone surfaces (6-22 {micro}m away) and increased the relative number more than 52 {micro}m away. These differences in vessel proximity to bone were driven by changes in the stroke-exercise group, indicating compounded effects of stroke and exercise. Exercise, but not stroke, nearly reduced the amount of osteogenic Type H blood vessels in the proximal tibial metaphysis, quantified with immunofluorescence microscopy.\n\nConclusionsThis study is the first to examine the effects of stroke on osteovasculature. Stroke increased the amount of osteovasculature, but since blood vessels close to bone are associated with bone remodeling, the shift in osteovascular structure could play a role in bone loss following stroke. The exercise-induced reduction in the amount of Type H vessels and the stroke-exercise effect on osteovascular structure suggest moderate aerobic activity may have detrimental effects on bone remodeling during early stroke recovery.

bioengineering↗

bioRxiv2019

Stroke prevents exercise-induced gains in bone microstructure but not composition in mice

Ischemic stroke induces rapid loss in bone mineral density that is up to 13 times greater than during normal aging, leading to a markedly increased risk of fracture. Little is known about skeletal changes following stroke beyond density loss. In this study we use a mild-moderate middle cerebral artery occlusion model to determine the effects of ischemic stroke without bedrest on bone microstructure, dynamic bone formation, and tissue composition. Twenty-seven 12-week-old male C57Bl/6J mice received either a stroke or sham surgery and then either received daily treadmill exercise or remained sedentary for four weeks. All mice were ambulatory immediately following stroke, and limb coordination during treadmill exercise was unaffected by stroke, indicating similar mechanical loading across limbs for both stroke and sham groups. Stroke did not directly detriment microstructure, but exercise only stimulated adaptation in the sham group, not the stroke group, with increased bone volume fraction and trabecular thickness in the sham distal femoral metaphysis. Stroke differentially decreased cortical area in the affected limb relative to the unaffected limb of the distal femoral metaphysis, as well as endosteal bone formation rate in the affected tibial diaphysis. Although exercise failed to improve bone microstructure following stroke, exercise increased mineral-to-matrix content in stroke but not sham. Together, these results show that stroke inhibits exercise-induced changes to femoral microstructure but not tibial composition, even without changes to gait. Similarly, affected-unaffected limb differences in cortical bone structure and bone formation rate in ambulatory mice show that stroke affects bone health even without bedrest.

bioengineering↗

bioRxiv2019

Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology

Tissue-wide electrophysiology with single-cell and millisecond spatiotemporal resolution is critical for heart and brain studies, yet issues arise from invasive, localized implantation of electronics that destructs the well-connected cellular networks within matured organs. Here, we report the creation of cyborg organoids: the three-dimensional (3D) assembly of soft, stretchable mesh nanoelectronics across the entire organoid by cell-cell attraction forces from 2D-to-3D tissue reconfiguration during organogenesis. We demonstrate that stretchable mesh nanoelectronics can grow into and migrate with the initial 2D cell layers to form the 3D structure with minimal interruptions to tissue growth and differentiation. The intimate contact of nanoelectronics to cells enables us to chronically and systematically observe the evolution, propagation and synchronization of the bursting dynamics in human cardiac organoids through their entire organogenesis.

bioengineering↗

bioRxiv2019

Blood-brain barrier dysfunction in aging induces hyper-activation of TGF-beta signaling and chronic yet reversible neural dysfunction

Aging involves a decline in neural function that contributes to cognitive impairment and disease. However, the mechanisms underlying the transition from a young-and-healthy to aged-and-dysfunctional brain are not well understood. Here, we report breakdown of the vascular blood-brain barrier (BBB) in aging humans and rodents, which begins as early as middle age and progresses to the end of the lifespan. Gain-of-function and loss-of-function manipulations show that this BBB dysfunction triggers hyperactivation of transforming growth factor {beta} (TGF{beta}) signaling in astrocytes, which is necessary and sufficient to cause neural dysfunction and age-related pathology. Specifically, infusion of the serum protein albumin into the young brain (mimicking BBB leakiness) induced astrocytic TGF{beta} signaling and an aged brain phenotype including aberrant electrocorticographic activity, vulnerability to seizures, and cognitive impairment. Furthermore, conditional genetic knockdown of astrocytic TGF{beta} receptors, or pharmacological inhibition of TGF{beta} signaling, reversed these symptomatic outcomes in aged mice. Finally, we found that this same signaling pathway is activated in aging human subjects with BBB dysfunction. Our study identifies dysfunction in the neurovascular unit as one of the earliest triggers of neurological aging, and demonstrates that the aging brain may retain considerable latent capacity which can be revitalized by therapeutic inhibition of TGF{beta} signaling.

neuroscience↗