Damage to the Optic Chiasm in Myelin Oligodendrocyte Glycoprotein–Experimental Autoimmune Encephalomyelitis Mice

Herrera, Sheryl L.; Palmer, Vanessa L.; Whittaker, Heather; Smith, Blair Cardigan; Kim, Annie; Schellenberg, Angela E; Thiessen, Jonathan D.; Buist, Richard; Bigio, Marc R. Del; Martin, Melanie

doi:10.4137/mri.s19750

Cited by 6 publications

(6 citation statements)

References 61 publications

(129 reference statements)

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“…Similar to findings in human studies, alterations in the retina [8, 9], optic nerve [10–13], tract [11, 12], chiasm [14], and radiations [15] have been reported in mouse models of MS. Approximately 70–92% of eyes develop ON 11 days post immunisation (dpi) in experimental ON mouse models, making it ideal for investigating visual pathway dysfunction [11, 16, 17].…”

Section: Introductionsupporting

confidence: 73%

Retinal pathology in experimental optic neuritis is characterized by retrograde degeneration and gliosis

Manogaran

Samardzija

Schad

et al. 2019

acta neuropathol commun

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The exact mechanisms and temporal sequence of neurodegeneration in multiple sclerosis are still unresolved. The visual pathway including its unmyelinated retinal axons, can serve as a prototypic model of neurodegeneration in experimental optic neuritis. We conducted a longitudinal study combining retinal imaging through optical coherence tomography (OCT) with immunohistochemical analyses of retinal and optic nerve tissue at various time points in experimental autoimmune encephalomyelitis (EAE). Inner retinal layer (IRL) thickness was measured in 30 EAE and 14 healthy control C57BL/6 J mice using OCT. Distribution of marker proteins was assessed by immunofluorescence staining and retinal mRNA levels were assayed using real-time PCR. Histological morphology was evaluated on light and electron microscopy images. Signs of inflammatory edema 11 days post immunisation coincided with IRL thickening, while neuro-axonal degeneration throughout the disease course contributed to IRL thinning observed after 20 days post immunisation. Retinal pathology, including axonal transport impairment, was observed early, prior to cellular infiltration (i.e. T-cells) in the optic nerve 11 days post immunisation. Yet, the effects of early retinal damage on OCT-derived readouts were outweighed by the initial inflammatory edema. Early microglial activation and astrocytosis was detected in the retina prior to retinal ganglion cell loss and persisted until 33 days post immunisation. Müller cell reactivity (i.e. aquaporin-4 and glutamine synthetase decrease) presented after 11 days post immunisation in the IRL. Severe neuro-axonal degeneration was observed in the optic nerve and retina until 33 days post immunisation. Initial signs of retinal pathology subsequent to early glial activity, suggests a need for prophylactic treatment of optic neuritis. Following early inflammation, Müller cells possibly respond to retinal pathology with compensatory mechanisms. Although the majority of the IRL damage observed is likely due to retrograde degeneration following optic neuritis, initial pathology, possibly due to gliosis, may contribute further to IRL thinning. These results add morphological substrate to our OCT findings. The extent and rapid onset of axonal and neuronal damage in this model appears relevant for testing interventions scaled to human optic neuritis. Electronic supplementary material The online version of this article (10.1186/s40478-019-0768-5) contains supplementary material, which is available to authorized users.

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Section: Introductionsupporting

confidence: 73%

Retinal pathology in experimental optic neuritis is characterized by retrograde degeneration and gliosis

Manogaran

Samardzija

Schad

et al. 2019

acta neuropathol commun

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“…WMH is commonly detected in the CNS of EAE animals. These lesions, which are observed to precede the onset of clinical signs (Chuhutin et al, 2020; Waiczies et al, 2012), are spotted in the periventricular WM, in the CC, in the thalamus, in the hippocampus (Belloli et al, 2018; Boretius et al, 2012), in the optic tract (Herrera et al, 2014), in the spinal cord (Mori et al, 2014), and the cerebellum (Belloli et al, 2018; Waiczies et al, 2012) (Figure 2). Histopathological analysis of spinal cords and brains confirmed the association between the radiological outcomes and neuropathological features.…”

Section: Mri Studies In Ms Mouse Modelsmentioning

confidence: 99%

“…Histopathological analysis of spinal cords and brains confirmed the association between the radiological outcomes and neuropathological features. The pathological changes with EAE progression were examined for inflammation, for example, hematoxylin and eosin (H&E), T‐cell infiltration (CD4 and CD3) and immunoglobulins, activation of microglia/macrophages (Iba1 and Mac3), and astrogliosis (GFAP), as well as demyelination (MBP and luxol fast blue‐LFB) and acute axonal damage (amyloid precursor protein‐APP) (Belloli et al, 2018; Boretius et al, 2012; Herrera et al, 2014; Waiczies et al, 2012).…”

Section: Mri Studies In Ms Mouse Modelsmentioning

confidence: 99%

Magnetic resonance imaging approaches for studying mouse models of multiple sclerosis: A mini review

Gilli

Ceccarelli

2023

J of Neuroscience Research

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Given that multiple sclerosis (MS) is a complex disease with an unclear etiology, a single animal model is unlikely to accurately represent all aspects of pathology and clinical features of the human condition. However, the availability of three major types of murine models of MS, that is, experimental autoimmune encephalomyelitis (EAE), viral models, and toxic models, enables studies of several relevant features of this debilitating disease. Researchers have recently begun to combine magnetic resonance imaging (MRI) technologies with other experimental strategies to acquire complementary information, for example, anatomical and functional, and study the effect of experimental manipulations longitudinally in a noninvasive way. This review summarizes the latest MRI studies investigating critical aspects of MS, such as atrophy, demyelination, neuroaxonal damage, and neuroinflammation, in mouse models of MS. Advanced techniques will be briefly discussed, providing references to specialized literature for the readers. Thus, this review aims to describe different imaging protocols used to study critical aspects of MS in a research laboratory, discussing the main related findings in the most significant murine models of the disease.

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“…A rare aetiology like chronic chiasmal arachnoiditis can only be suspected by alteration in dimensions of optic chiasma where presence of fibrous cicatricial bands causes chiasmal compression. (16) However, chiasmal neuritis (17) resulting from aetiologies ranging from idiopathic, demyelinating disease, (17,18) infections, etc. cannot be confirmed by chiasmal measurements.…”

Section: Slmentioning

confidence: 99%

A Study of Normal Mri Measurements of Optic Chiasma and Its Correlation With Perichiasmal Lesions

Sharma¹,

Sharma²

2016

jebmh

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BACKGROUND Cranial MRI is routinely performed in which optic chiasma is visualised as part of optic pathways. Chiasma can be affected by various pathologies. Its deviation from normal dimensions can easily be calculated on routine cranial MRI. METHOD This study was done retrospectively evaluating twenty consecutive cranial MRI examinations. T2WI images were included in this study as it was a part of routine protocol and were used for evaluation. One case from another setup was included in this study to highlight the importance of measurements. RESULTS The normal and abnormal measurements were calculated with submillimetre digital caliper and are described in Table 1-2. The parameters used were width, height and area of optic chiasma. CONCLUSION This study highlights the usefulness of evaluating optic chiasma to diagnose various visual and nonvisual-related conditions. Objective measurements of optic chiasma should be done routinely in T2WI coronal images.

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Damage to the Optic Chiasm in Myelin Oligodendrocyte Glycoprotein–Experimental Autoimmune Encephalomyelitis Mice

Cited by 6 publications

References 61 publications

Retinal pathology in experimental optic neuritis is characterized by retrograde degeneration and gliosis

Retinal pathology in experimental optic neuritis is characterized by retrograde degeneration and gliosis

Magnetic resonance imaging approaches for studying mouse models of multiple sclerosis: A mini review

A Study of Normal Mri Measurements of Optic Chiasma and Its Correlation With Perichiasmal Lesions

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