High-Sensitivity Non-Invasive Microwave Glucose Sensor with ZnO/CNT Composite Optimized by Deep Learning for Wearable Medical Devices.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system (CNS) that primarily affects the optic nerves and spinal cord. It is characterized by severe, recurrent episodes of optic neuritis (ON), often resulting in irreversible vision loss and myelitis, and is especially prevalent in Asian populations (Wingerchuk et al., 2015; Tian et al., 2020). NMOSD is frequently linked to pathogenic autoantibodies targeting aquaporin-4 (AQP4), a water channel protein abundantly found on the foot processes of astrocytes, and activation of the complement system, characterized by deposition of complement components such as C5b-9 (Lennon et al., 2005; Wingerchuk et al., 2015; Weinshenker and Wingerchuk, 2017; Asavapanumas et al., 2021). Astrocytes express two isoforms of AQP4, M1 and M23. M23 forms tetramers and orthogonal arrays of particles that bind strongly to AQP4-immunoglobulin G (IgG), while M1 reduces orthogonal arrays of particle size. rAb53 binds more strongly to M23 than rAb58 does, making it more effective at inhibiting AQP4 function (Landis and Reese, 1974; Bennett et al., 2009; Crane and Verkman, 2009; Crane et al., 2011; Wolburg et al., 2011; Phuan et al., 2012; Rossi et al., 2012; Saadoun et al., 2013). AQP4-IgG binding to AQP4 on astrocytes activates the complement system and microglia, which are the primary responders to these signals (Lucchinetti et al., 2014; Chen et al., 2020, 2021; Moinfar and Zamvil, 2020). Cytokines such as interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, and C–X–C motif chemokine ligand 10 (CXCL10) influence microglial development and activation. Activated microglia release proinflammatory cytokines, which can harm nearby neurons if activation is chronic (Sui et al., 2006; Wilms et al., 2010; Matsushita et al., 2013; Saadoun et al., 2013; Asavapanumas et al., 2014b; Bradl and Lassmann, 2014; Bennett et al., 2015; West et al., 2019; Fujihara et al., 2020; Yang et al., 2020; Soerensen et al., 2021). In NMOSD-related ON (NMOSD-ON), this inflammation depletes retinal ganglion cells (RGCs) and causes optic nerve degeneration (Asavapanumas et al., 2014b; Bennett et al., 2015; Ransohoff, 2016; Tang and Le, 2016; Oertel et al., 2018; Yang et al., 2020; Oertel et al., 2021; Vegda et al., 2023). In autoimmune diseases, CNS microglia and astrocytes secrete brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which regulate neuroinflammation and neuroprotection, thereby, enhancing neuroplasticity and promoting neuronal survival (De Simone et al., 2007; Rizzi et al., 2018; Tiberi et al., 2022; Nociti and Romozzi, 2023). The previous investigator attempted to replicate NMOSD-ON through multiple methodologies. The systemic administration of AQP4-IgG in NMOSD-ON may initiate primary demyelination and complicate the ultimate results (Kurosawa et al., 2015; Hillebrand et al., 2019; Remlinger et al., 2023a). Additionally, the localized application of AQP4-IgG to the anterior optic nerve effectively induces NMOSD-ON; however, NMOSD-ON predominantly manifests within the posterior optic nerve (Felix et al., 2016; Zhang et al., 2018; Soerensen et al., 2021; Uzawa et al., 2024). Moreover, previous studies have highlighted the impact of AQP4-IgG on astrocyte damage in the NMOSD-ON animal model. However, the cascading effects on other cell types, such as microglia, oligodendrocytes, and RGCs, remain incompletely understood (Marignier et al., 2016; Sagan et al., 2016). The absence of a detailed timeline for changes like AQP4 loss, astrocyte damage, microglial activation, demyelination, and RGC degeneration in NMOSD-ON hinders the prediction of disease progression and the identification of a disease timeframe (Asavapanumas et al., 2014a, b; Asavapanumas and Verkman, 2014; Bradl and Lassmann, 2014; Zhang et al., 2018; Soerensen et al., 2021). The aim of this study was to delineate the timeline of disease progression and correlate histological and molecular findings with functional outcomes post-initiation of NMOSD-ON in an optimized animal model. By establishing a comprehensive timeline, we aimed to identify critical windows of disease progression, thereby improving our understanding of NMOSD-ON development.