Biology subjects

Delphin, A.

Publications and source records attributed to Delphin, A..

3 recordsLinked to original sources

bioRxiv2026

Revealing multiscale architecture of the intact human spine using hierarchical phase contrast tomography

Background: Computed tomography (CT) and magnetic resonance imaging (MRI) provide detailed clinical assessment of the human spine; however, their millimeter-scale spatial resolution limits direct visualization of tissue microarchitecture and interfaces. Hierarchical phase-contrast tomography (HiP-CT) enables ex vivo non-destructive, micron-resolution imaging of intact human organs without exogenous contrast agents, extending anatomical assessment to spatial scales inaccessible to conventional clinical imaging. Purpose: To evaluate the capability of HiP-CT to visualize macro- to microanatomy of an intact adult human spine ex vivo. Methods: An intact spine (C1-L5) from a 62-year-old male donor without known skeletal disease was formalin-fixed and imaged by HiP-CT at the European Synchrotron. Whole-spine imaging was performed at 16.26 m isotropic voxels, with selected regions of interest imaged using 2.2 m voxels. Ex vivo MRI using clinical sequences was performed for anatomical comparison. Three-dimensional segmentation and quantitative analyses included intervertebral disc (IVD) grading, annulus fibrosus fiber tracing, and vertebral trabecular micro-morphometry. Results: HiP-CT enabled high spatial-resolution, multiscale imaging of the intact human spine, simultaneously visualizing vertebral bone and endplate, IVDs, spinal cord and meninges, nerve roots and ganglia, vasculature, ligaments, and musculature. Three-dimensional segmentation and virtual sectioning mapped neurovascular anatomy and vertebral vascular supply, without exogenous contrast enhancement, while preserving their relationships with surrounding tissues. Whole-spine images enabled quantitative analysis of annulus fibrosus fiber organization and vertebral trabecular microarchitecture, permitting the detection of focal posterolateral fiber disruption at the L4-L5 IVD and regional differences in trabecular architecture between cervical and lumbar vertebral bodies. Local tomography resolved annulus fibrosus lamellae, vertebral endplate Haversian systems, and facet joint hyaline cartilage at micron resolution. Conclusions: HiP-CT enables non-destructive, multiscale three-dimensional imaging of the intact human spine while preserving tissue relationships across spatial scales and hard-soft tissue boundaries. HiP-CT could provide an ex vivo microanatomical reference for future correlation with clinical imaging investigations of spinal disease and in the development and validation of imaging biomarkers.

bioengineering↗

bioRxiv2026

Intermittent Hypoxia Alters Cerebrovascular Recovery After Stroke

Stroke is a prevalent chronic disease, significantly contributing to mortality and long-term disability. The cerebrovascular recovery process after stroke can be complicated by certain comorbidities, including obstructive sleep apnea syndrome (OSA). However, the mechanisms underlying this deleterious impact of OSA on post-stroke recovery remain elusive. We conducted a preclinical study in rats submitted to stroke and intermittent hypoxia (IH), the main characteristic of OSA, to investigate the effects of IH on stroke lesion and to decipher the pathophysiological mechanisms of this stroke-OSA interaction. Using a malonate model of ischemic stroke on Sprague Dawley rats exposed to either normoxia or intermittent hypoxia for over 56 days, we monitored brain lesion size, microvascular plasticity and blood brain barrier (BBB) permeability using in vivo 4.7T-MRI. Finally, we assessed oxidative stress, inflammation, and angiogenesis-related gene expression by qPCR, and NeuN, GFAP, Collagen IV and ZO-1 expression by immunohistological staining. Our findings indicate that while IH does not significantly affect lesion volume reduction over time, it exacerbates ischemic injury-induced necrosis and neuronal loss. Additionally, IH amplifies post-stroke inflammation, as evidenced by increased IL-6 and TGF-{beta} expression, and induces oxidative stress by increasing DHE staining and decreasing Superoxide Dismutase (SOD1) level. Vascular assessment revealed IH-induced modifications in vessel radius and angiogenic factors expression (VEGF, Ang2), alongside increased BBB permeability and altered expression of aquaporin 1 and claudin 1, particularly in the acute phase post-stroke. These results suggest that IH alters cerebrovascular integrity and exacerbates inflammatory response following ischemic stroke, potentially contributing to poorer long-term functional outcomes. Understanding the mechanisms through which IH exacerbates post-stroke injury may guide the development of targeted neuroprotective strategies to improve stroke recovery in patients with OSA.

pathology↗

bioRxiv2025

Multimodal Characterization and Evolution of Malonate-induced Stroke Model: advanced MRI, Histology-Molecular Profiling

BackgroundIschemic stroke is a leading cause of mortality and disability worldwide, yet therapeutic options remain limited. Preclinical models play a crucial role in understanding stroke pathophysiology and evaluating potential treatments. This study aimed to provide a comprehensive characterization of the temporal evolution of ischemic injury induced by malonate intracerebral injection using multiparametric magnetic resonance imaging (MRI) combined with histological and molecular analysis. MethodsFocal ischemic lesions were induced by malonate injection in the striatum of rats. Lesion volume was monitored using T2-weighted MRI at multiple time points (Day 1, D7, D14, D28, and D56). Water content, reflecting vasogenic edema, was assessed via apparent diffusion coefficient (ADC) measurements, while vascular alterations were evaluated using blood volume fraction (BVF), vessel radius, and oxygen saturation (StO2). Blood-brain barrier (BBB) permeability was quantified through gadolinium-enhanced MRI. Molecular analyses by RT-qPCR were conducted to assess oxidative stress, inflammation, and angiogenesis-related gene expression. Immunohistological staining was performed to investigate neuronal loss, astrocytic activation, and vascular remodeling. ResultsMRI analysis showed a significant and progressive decrease in lesion volume. Water content increased from D4 onward. Ischemic injury significantly altered vascular function, leading to increased vessel radius and BVF while reducing tissue oxygenation. BBB permeability was elevated at D7 and D56, accompanied by increased claudin-1 and aquaporin-1 expression. Molecular analysis revealed an upregulation of inflammatory markers (IL-6, TGF-{beta}, NF-{kappa}B), oxidative stress response genes (SOD1, Nrf1), and impaired angiogenesis with increased Ang1/Ang2 but reduced VEGF/VEGFR1. Immunohistological analysis demonstrated neuronal loss, astrocytic activation, and vascular remodeling, characterized by increased ZO-1 and ColI-IV expression. ConclusionThe observed changes in lesion volume, vascular function, inflammation, oxidative stress, and angiogenesis highlight key mechanisms underlying post-stroke recovery. These findings emphasize the importance of long-term monitoring in preclinical stroke models and may contribute to the development of novel therapeutic strategies.

neuroscience↗