MRI in experimental inflammatory and mitochondrial optic neuropathies

Guy, John

doi:10.1002/nbm.1309

Cited by 8 publications

(6 citation statements)

References 58 publications

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“…IHC results indicated that the mice with higher transport rates suffered less axon and myelin damage than those with slower transport rates. It is possible that acute vasogenic edema at the ON onset impeded action potential propagation and thus reduced VA without significant axonal pathologies (Guy, 2008; Hickman et al, 2004). It is also worth noting that VA was employed herein to serve as a “clinical” sign of optic neuritis in EAE mice because the conventional clinical score reflecting spinal cord injury does not correspond to visual functions.…”

Section: Discussionmentioning

confidence: 99%

“…As a paramagnetic ion, Mn 2+ reduces tissue water T1 relaxation time and its presence in tissues can be identified as hyper-intensities in the T1W image (Silva et al, 2004). Recently, MEMRI has been applied to examine pathologies of the optic nerve, including blood-brain barrier integrity or inflammation, in EAE rats and mice (Boretius et al, 2008; Gadjanski et al, 2009; Guy, 2008). In this study, MEMRI was further extended as a dynamic tracer to investigate in vivo axonal transport integrity assessing axonal transport rates quantitatively.…”

Section: Introductionmentioning

confidence: 99%

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Axonal transport rate decreased at the onset of optic neuritis in EAE mice

et al. 2014

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Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn2+ accumulation rate (in % signal change/hour) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn2+ transport rate (in mm/hour) by measuring the rate of change in optic nerve length enhanced by Mn2+. Compared to sham-treated healthy mice, Mn2+ accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn2+ was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Axonal transport rate decreased at the onset of optic neuritis in EAE mice

et al. 2014

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“…MRI has been used to study the effect of treatments for optic neuritis animal models. 32 The disruption of the blood-brain barrier (BBB) and demyelination in an EAE optic neuritis guinea pig model was studied using T 2 -weighted and Gd-diethylene-triaminepentacetate (DTPA)–enhanced T 1 -weighted MRI. 33 Changes in MR images corresponded with optic nerve abnormalities and were lessened with catalase detoxification of endogenous H 2 O 2 in these mice.…”

Section: Introductionmentioning

confidence: 99%

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

Herrera

Palmer

Whittaker

et al. 2014

Magn Reson�Insights

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Optic chiasm lesions in myelin oligodendrocyte glycoprotein (MOG)–experimental autoimmune encephalomyelitis (EAE) mice were characterized using magnetic resonance imaging (MRI) and validated using electron microscopy (EM). MR images were collected from 3 days after induction to remission, approximately 20 days after induction. Hematoxylin and eosin, solochrome cyanin–stained sections, and EM images were obtained from the optic chiasms of some mice approximately 4 days after disease onset when their scores were thought to be the highest. T2-weighted imaging and apparent diffusion coefficient map hyperintensities corresponded to abnormalities in the optic chiasms of EAE mice. Mixed inflammation was concentrated at the lateral surface. Degeneration of oligodendrocytes, myelin, and early axonal damage were also apparent. A marked increase in chiasm thickness was observed. T2-weighted and diffusion-weighted MRI can detect abnormalities in the optic chiasms of MOG-EAE mice. MRI is an important method in the study of this model toward understanding optic neuritis.

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“…In this study, the experimental autoimmune encephalomyelitis (EAE) model was used to study the onset and progression of ON as well as the efficacy of intervention with a putative neuroprotective compound. Serial magnetic resonance imaging (MRI) studies of a prospective cohort of EAE mice revealed that disruption of the blood–optic nerve barrier began as early as 3 days post‐immunization and resolved spontaneously at 2 weeks (Guy ). This suggests that ON may be an early event during EAE progression.…”

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confidence: 99%

Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis

Smith

Rohrer

Wheless

et al. 2016

Journal of Neurochemistry

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Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with multiple sclerosis (MS). ON pathology is characterized by attack of autoreactive T cells against optic nerve antigens, resulting in demyelination, death of retinal ganglion cells (RGCs) and cumulative visual impairment. A model of experimental autoimmune encephalomyelitis (EAE) was utilized to study the onset and progression of ON and the neuroprotective efficacy of oral treatment with the calpain inhibitor SNJ 1945. EAE was actively induced in B10.PL mice with myelin basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ 1945 from Day 9 until sacrifice (Day 26). Visual function was determined by electroretinogram (ERG) recordings and daily measurement of optokinetic responses (OKR) to a changing pattern stimulus. Optic nerve and retinal histopathology was investigated by immunohistochemical and luxol fast blue staining. EAE mice manifested losses in OKR thresholds, a measurement of visual acuity, which began early in the disease course. There was a significant bias towards unilateral OKR impairment among EAE-ON eyes. Treatment with SNJ 1945, initiated after the onset of OKR threshold decline, improved visual acuity, pattern ERG amplitudes and paralysis, with attenuation of RGC death. Furthermore, calpain inhibition spared oligodendrocytes, prevented degradation of axonal neurofilament protein, and attenuated reactive astrocytosis. The trend of early, unilateral visual impairment in EAE-ON parallels the clinical presentation of ON exacerbations associated with MS. Calpain inhibition may represent an ideal candidate therapy for the preservation of vision in clinical ON.

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MRI in experimental inflammatory and mitochondrial optic neuropathies

Cited by 8 publications

References 58 publications

Axonal transport rate decreased at the onset of optic neuritis in EAE mice

Axonal transport rate decreased at the onset of optic neuritis in EAE mice

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

Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis

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