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Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intracerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon cauterization of the dCLN afferent lymphatics and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke., (© 2024 Boisserand et al.)

Meningeal lymphatic vessels promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelium growth factor-C (VEGF-C) is essential for meningeal lymphatic development and maintenance and has therapeutic potential for treating neurological disorders, including ischemic stroke. We have investigated the effects of VEGF-C overexpression on brain fluid drainage, single cell transcriptome in the brain, and stroke outcomes in adult mice. Intra-cerebrospinal fluid administration of an adeno-associated virus expressing VEGF-C (AAV-VEGF-C) increases the CNS lymphatic network. Post-contrast T1 mapping of the head and neck showed that deep cervical lymph node size and drainage of CNS-derived fluids were increased. Single nuclei RNA sequencing revealed a neuro-supportive role of VEGF-C via upregulation of calcium and brain-derived neurotrophic factor (BDNF) signaling pathways in brain cells. In a mouse model of ischemic stroke, AAV-VEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage. AAV-VEGF-C thus promotes CNS-derived fluid and solute drainage, confers neuroprotection, and reduces ischemic stroke damage., Short Abstract: Intrathecal delivery of VEGF-C increases the lymphatic drainage of brain-derived fluids confers neuroprotection, and improves neurological outcomes after ischemic stroke.

Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations after OVA-A555 tracer injection into the cerebrospinal fluid (CSF) and performed real-time vessel-wall (VW) magnetic resonance imaging (VW-MRI) after systemic injection of gadobutrol in patients with neurological pathologies. We observed a conserved three-dimensional anatomy of MLVs in mice and humans that aligned with dural venous sinuses but not with nasal CSF outflow, and we discovered an extended anterior MLV network around the cavernous sinus, with exit routes through the foramina of emissary veins. VW-MRI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases., (© 2022 Jacob et al.)

Scanning near-field optical microscopes (SNOM's) actually lead to nanometric lateral resolution. A combination with shear-force feedback is sometimes used to keep the SNOM tip at a constant force from the sample. However, resolutions in shear-force and optical data are different. An estimation of both resolutions is important for characterizing the capabilities of such systems. The basic principle of the measurement is to compare a spline-fitted logarithm of the power spectra calculated with the optical image with that of the shear force image in which resolution is determined a priori. Quantitative results are given in the case of periodic or untested sample and simulated data. Moreover the accuracy and the stability of the method are discussed.

We discuss a model that describes the optical interactions between a dielectric tip and a surface exhibiting roughness of subwavelength size (infinite tracks). Such a model gives new insight into the resolution achievable by scanning near field optical microscopy. The dielectric tip is schematized as a cone whose extremity reduces to a small sphere acting as a dipolar scattering center, allowing separation of the contributions from the near field lying at the air-sample interface of other long range terms associated with the progressive waves coming from the surface. It is shown that because of its fast spatial dependence, the near field detected by the tip contains subwavelength features of the object. Relationships with preliminary experiments are discussed.

Two configurations of a scanning near field optical microscope working in reflection are presented. Results exhibiting nanometric resolution are given and discussed.

The notion of the coefficient of correlation between two interfering wave fronts is applied to the study of fringe formation and visibility in speckle interferometry. The parameters affecting the visibility of the in-plane displacement fringes are analyzed in the case of an arbitrary displacement and deformation of the object surface. The influence of strain as well as defocusing on the visibility is explicated. Physical significance of the results is discussed. The work is partly backed by experimental investigation.