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1.
Nature ; 628(8008): 612-619, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38509366

RESUMEN

There is increasing interest in how immune cells in the meninges-the membranes that surround the brain and spinal cord-contribute to homeostasis and disease in the central nervous system1,2. The outer layer of the meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and functions as a site for B cell development3-6. Here we identify organized lymphoid structures that protect fenestrated vasculature in the dura mater. The most elaborate of these dural-associated lymphoid tissues (DALT) surrounded the rostral-rhinal confluence of the sinuses and included lymphatic vessels. We termed this structure, which interfaces with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or after challenge with systemic or nasal antigens. DALT contain germinal centre B cells and support the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate a lymphoid structure around vasculature in the dura mater that can sample antigens and rapidly support humoral immune responses after local pathogen challenge.


Asunto(s)
Duramadre , Inmunidad Humoral , Tejido Linfoide , Venas , Administración Intranasal , Antígenos/administración & dosificación , Antígenos/inmunología , Médula Ósea/inmunología , Sistema Nervioso Central/irrigación sanguínea , Sistema Nervioso Central/inmunología , Duramadre/irrigación sanguínea , Duramadre/inmunología , Centro Germinal/citología , Centro Germinal/inmunología , Vasos Linfáticos/inmunología , Tejido Linfoide/irrigación sanguínea , Tejido Linfoide/inmunología , Células Plasmáticas/inmunología , Cráneo/irrigación sanguínea , Linfocitos T/inmunología , Venas/fisiología , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Animales , Ratones , Anciano de 80 o más Años
4.
bioRxiv ; 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36909631

RESUMEN

Whole-brain fluorescence images require several stages of computational processing to fully reveal the neuron morphology and connectivity information they contain. However, these computational tools are rarely part of an integrated pipeline. Here we present BrainLine, an open-source pipeline that interfaces with existing software to provide registration, axon segmentation, soma detection, visualization and analysis of results. By implementing a feedback based training paradigm with BrainLine, we were able to use a single learning algorithm to accurately process a diverse set of whole-brain images generated by light-sheet microscopy. BrainLine is available as part of our Python package brainlit: http://brainlit.neurodata.io/ .

5.
STAR Protoc ; 4(3): 102367, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37339049

RESUMEN

Mapping cranial vasculature and adjacent neurovascular interfaces in their entirety will enhance our understanding of central nervous system function in any physiologic state. We present a workflow to visualize in situ murine vasculature and surrounding cranial structures using terminal polymer casting of vessels, iterative sample processing and image acquisition, and automated image registration and processing. While this method does not obtain dynamic imaging due to mouse sacrifice, these studies can be performed before sacrifice and processed with other acquired images. For complete details on the use and execution of this protocol, please refer to Rosenblum et al.1.


Asunto(s)
Cráneo , Animales , Ratones , Flujo de Trabajo
6.
Cell Rep Methods ; 2(1)2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-35373177

RESUMEN

Understanding physiologic and pathologic central nervous system function depends on our ability to map the entire in situ cranial vasculature and neurovascular interfaces. To accomplish this, we developed a non-invasive workflow to visualize murine cranial vasculature via polymer casting of vessels, iterative sample processing and micro-computed tomography, and automatic deformable image registration, feature extraction, and visualization. This methodology is applicable to any tissue and allows rapid exploration of normal and altered pathologic states.


Asunto(s)
Sistema Cardiovascular , Ratones , Animales , Microtomografía por Rayos X/métodos , Cráneo/diagnóstico por imagen
7.
Front Neurol ; 12: 699674, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34335453

RESUMEN

The inner ear is a complex organ housed within the petrous bone of the skull. Its intimate relationship with the brain enables the transmission of auditory and vestibular signals via cranial nerves. Development of this structure from neural crest begins in utero and continues into early adulthood. However, the anatomy of the murine inner ear has only been well-characterized from early embryogenesis to post-natal day 6. Inner ear and skull base development continue into the post-natal period in mice and early adulthood in humans. Traditional methods used to evaluate the inner ear in animal models, such as histologic sectioning or paint-fill and corrosion, cannot visualize this complex anatomy in situ. Further, as the petrous bone ossifies in the postnatal period, these traditional techniques become increasingly difficult. Advances in modern imaging, including high resolution Micro-CT and MRI, now allow for 3D visualization of the in situ anatomy of organs such as the inner ear. Here, we present a longitudinal atlas of the murine inner ear using high resolution ex vivo Micro-CT and MRI.

8.
JCI Insight ; 6(21)2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34546977

RESUMEN

We recently described a transtentorial venous system (TTVS), which to our knowledge was previously unknown, connecting venous drainage throughout the brain in humans. Prior to this finding, it was believed that the embryologic tentorial plexus regresses, resulting in a largely avascular tentorium. Our finding contradicted this understanding and necessitated further investigation into the development of the TTVS. Herein, we sought to investigate mice as a model to study the development of this system. First, using vascular casting and ex vivo micro-CT, we demonstrated that this TTVS is conserved in adult mice. Next, using high-resolution MRI, we identified the primitive tentorial venous plexus in the murine embryo at day 14.5. We also found that, at this embryologic stage, the tentorial plexus drains the choroid plexus. Finally, using vascular casting and micro-CT, we found that the TTVS is the dominant venous drainage in the early postnatal period (P8). Herein, we demonstrated that the TTVS is conserved between mice and humans, and we present a longitudinal study of its development. In addition, our findings establish mice as a translational model for further study of this system and its relationship to intracranial physiology.


Asunto(s)
Venas/anatomía & histología , Venas/diagnóstico por imagen , Animales , Humanos , Ratones
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