scholarly journals Functional evolution of visual involvement in experimental autoimmune encephalomyelitis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732096347
Author(s):  
Silvia Marenna ◽  
Su-Chun Huang ◽  
Valerio Castoldi ◽  
Raffaele d’Isa ◽  
Gloria Dalla Costa ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Axonal Loss ◽  
Autoimmune Encephalomyelitis ◽  
Non Invasive ◽  
Vep Latency ◽  
Experimental Autoimmune ◽  
Motor Onset

Background Experimental autoimmune encephalomyelitis (EAE) is a common animal model of multiple sclerosis (MS). C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein exhibit chronic disease course, together with optic neuritis, consisting of demyelination/axonal loss of the optic nerve. Objectives To characterize functional and structural visual damages in two different phases of EAE: pre- and post-motor onset. Methods Visual alterations were detected with Visual Evoked Potential (VEP), Electroretinogram (ERG) and Optical Coherence Tomography (OCT). Optic nerve histology was performed at 7 (pre-motor onset) or 37 (post-motor onset) days post-immunization (dpi). Results At 7 dpi, optic nerve inflammation was similar in EAE eyes with and without VEP latency delay. Demyelination was detected in EAE eyes with latency delay (p < 0.0001), while axonal loss (p < 0.0001) and ERG b-wave amplitude (p = 0.004) were decreased in EAE eyes without latency delay compared to Healthy controls. At 37 dpi, functional and structural optic nerve damage were comparable between EAE groups, while a decrease of ERG amplitude and NGCC thickness were found in EAE eyes with VEP latency delay detected post-motor onset. Conclusions Thanks to non-invasive methods, we studied the visual system in a MS model, which could be useful for developing specific therapeutic strategies to target different disease phases.

scholarly journals Astrocytic YAP Protects the Optic Nerve and Retina in an Experimental Autoimmune Encephalomyelitis Model Through TGF-β Signaling

2021 ◽  
Author(s):  
qian Wu ◽  
Xuemeng Miao ◽  
Jingjing Zhang ◽  
Ludan Xiang ◽  
Xiuchun Li ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Optic Neuritis ◽  
Transforming Growth Factor ◽  
Conditional Knockout ◽  
Gene Set Enrichment Analysis ◽  
Tunel Staining ◽  
Autoimmune Encephalomyelitis ◽  
Gene Set ◽  
Experimental Autoimmune

Abstract BackgroundOptic neuritis, inflammation of the optic nerve (ON), is one of the main symptoms in multiple sclerosis (MS) and leads to visual disability. Astrocytes are pivotal regulators of neuroinflammation in MS. However, it remains unclear that the detailed roles and mechanisms of astrocytes in the neuroinflammation and demyelination in optic neuritis of MS. MethodsTo assess the role of YAP in ON and retina in response to experimental autoimmune encephalomyelitis (EAE), mice that conditionally knockout (CKO) YAP in astrocytes, namely YAP GFAP -CKO mice, were successfully generated. Immunostaining, Nissl staining, Hematoxylin-Eosin (HE) staining, TUNEL staining, luxol fast blue (LFB) staining, electron microscopy (EM), qRT-PCR and gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) by RNA sequencing were used to examine the roles of YAP pathway in EAE based on these conditional knockout mice. Inhibitors including SRI-011381 [an agonist of transforming growth factor-β (TGF-β) pathway] and XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) were used to further explore the molecular mechanism of YAP in ON and retina of EAE mice. Additionally, microglia and retinal ganglion cells (RGCs) counts, and demyelination and astrocytes were assessed by immunohistological staining. ResultsWe found that yes-associated protein (YAP) was significantly upregulated and activated in the astrocytes of ON in EAE. Conditional knockout YAP in astrocytes caused more severe inflammatory infiltration and demyelination in ON, and damage of the RGCs in EAE mice. Moreover, YAP deletion in astrocytes promoted the activation of astrocytes and microglia, but inhibited the proliferation of astrocytes of ON in EAE mice. Mechanically, TGF-β signaling pathway was significantly down-regulated after YAP deletion in astrocytes . Additionally, both qPCR and immunofluorescence assays confirmed the reduction of TGF-β 1 in YAP knockout ON astrocytes of EAE mice. Interestingly, SRI-011381 partially rescued the deficits in ON and retina of YAP knockout EAE mice. Finally, activation of YAP pathway relieved the neuroinflammation and demyelination in optic neuritis of EAE mice. ConclusionsThese results suggest astrocytic YAP may prevent the neuroinflammatory infiltration and demyelination through upregulation of TGF-β signaling and provide targets for the development of therapeutic strategies tailored for optic neuritis in MS.

scholarly journals Evoked potential and behavioral outcomes for experimental autoimmune encephalomyelitis in Lewis rats

2010 ◽  
Vol 31 (5) ◽  
pp. 595-601 ◽  
Author(s):  
Angelo H. All ◽  
Gracee Agrawal ◽  
Piotr Walczak ◽  
Anil Maybhate ◽  
Jeff W. M. Bulte ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Evoked Potential ◽  
Behavioral Outcomes ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

Evaluating potential therapies for bladder dysfunction in a mouse model of multiple sclerosis with high-resolution ultrasonography

2009 ◽  
Vol 15 (7) ◽  
pp. 795-801 ◽  
Author(s):  
S Al-Izki ◽  
G Pryce ◽  
G Giovannoni ◽  
D Baker
Keyword(s):  
Multiple Sclerosis ◽  
High Resolution ◽  
Animal Models ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Bladder Volume ◽  
Autoimmune Encephalomyelitis ◽  
Non Invasive ◽  
Bethanechol Chloride ◽  
Experimental Autoimmune

Background In multiple sclerosis (MS), demyelinating and neurodegenerative lesions develop throughout the central nervous system, which result in a loss of neurotransmission. As a result, people with MS exhibit a wide range of symptoms including dysfunction of the bladder, which can lead to urinary incontinence or retention. Such signs can develop in animal models of MS. Current assessments of bladder properties in animal models are generally invasive, electrophysiological techniques. Objective The use of a non-invasive, ultrasound system for measuring bladder volume in a mouse model of MS. Methods Chronic relapsing experimental autoimmune encephalomyelitis was induced in mice. The bladder volume was assessed using ultrasonography, during the disease course and following therapy with bethanechol chloride. Results It was demonstrated that volumes obtained ultrasonically positively-correlated (r = 0.960) with the urine volumes obtained by manual expression. It was also shown for the first time that bladder size increased significantly in mice with residual neurological deficit. Indeed, this increase in bladder size showed a strong, positive-correlation (r = 0.951) with the hind limb spasticity. Following treatment with bethanechol chloride, bladder volume significantly decreased in mice with chronic experimental autoimmune encephalomyelitis. Conclusion This study demonstrates a novel outcome measure in experimental MS that allows; repeated, non-invasive, high resolution ultrasonic monitoring of bladder function.

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