scholarly journals Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Reas S. Khan ◽  
Kimberly Dine ◽  
John G. Geisler ◽  
Kenneth S. Shindler
Keyword(s):  
Optic Neuritis ◽  
Demyelinating Disease ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
High Dose ◽  
Axonal Loss ◽  
Mitochondrial Uncoupling ◽  
The Central Nervous System ◽  
Mitochondrial Uncoupler

The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria’s physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis.

scholarly journals Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

2019 ◽  
Author(s):  
Jian Kang ◽  
Shu-Qing Liu ◽  
Yi-Fan Song ◽  
Meng-Ru Wang ◽  
Yao-Juan Chu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Disease Onset ◽  
High Dose ◽  
Retinal Ganglion ◽  
Autoimmune Encephalomyelitis

Abstract Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of blindness in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on ON in rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, and decreased apoptosis in retinal ganglion cells (RGCs) were also observed after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that causes blindness.

scholarly journals Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

2020 ◽  
Author(s):  
Jian Kang ◽  
Shu-Qing Liu ◽  
Yi-Fan Song ◽  
Meng-Ru Wang ◽  
Yao-Juan Chu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Disease Onset ◽  
High Dose ◽  
Retinal Ganglion ◽  
Autoimmune Encephalomyelitis

Abstract Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of blindness in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on ON in rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, and decreased apoptosis in retinal ganglion cells (RGCs) were also observed after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that causes blindness.

scholarly journals Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Atsuko Kimura ◽  
Kazuhiko Namekata ◽  
Xiaoli Guo ◽  
Takahiko Noro ◽  
Chikako Harada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Vision Loss ◽  
Demyelinating Disease ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Elevated Intraocular Pressure ◽  
The Central Nervous System

Glaucoma is a neurodegenerative disease of the eye and it is one of the leading causes of blindness. Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons, namely, the optic nerve, usually associated with elevated intraocular pressure (IOP). Current glaucoma therapies target reduction of IOP, but since RGC death is the cause of irreversible vision loss, neuroprotection may be an effective strategy for glaucoma treatment. One of the risk factors for glaucoma is increased oxidative stress, and drugs with antioxidative properties including valproic acid and spermidine, as well as inhibition of apoptosis signal-regulating kinase 1, an enzyme that is involved in oxidative stress, have been reported to prevent glaucomatous retinal degeneration in mouse models of glaucoma. Optic neuritis is a demyelinating inflammation of the optic nerve that presents with visual impairment and it is commonly associated with multiple sclerosis, a chronic demyelinating disease of the central nervous system. Although steroids are commonly used for treatment of optic neuritis, reduction of oxidative stress by approaches such as gene therapy is effective in ameliorating optic nerve demyelination in preclinical studies. In this review, we discuss oxidative stress as a therapeutic target for glaucoma and optic neuritis.

scholarly journals Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian Kang ◽  
Shuqing Liu ◽  
Yifan Song ◽  
Yaojuan Chu ◽  
Mengru Wang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Disease Onset ◽  
Visual Disturbance ◽  
High Dose ◽  
Retinal Ganglion ◽  
Akt Phosphorylation

AbstractInflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

scholarly journals Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

2020 ◽  
Author(s):  
Jian Kang ◽  
Shu-Qing Liu ◽  
Yi-Fan Song ◽  
Meng-Ru Wang ◽  
Yao-Juan Chu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Retinal Ganglion Cells ◽  
Cd4 T Cells ◽  
Ganglion Cells ◽  
Disease Onset ◽  
High Dose ◽  
Retinal Ganglion

Abstract Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs), and reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells were also observed in the retina after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica

2007 ◽  
Vol 13 (1) ◽  
pp. 128-132 ◽  
Author(s):  
S Watanabe ◽  
I Nakashima ◽  
T Misu ◽  
I Miyazawa ◽  
Y Shiga ◽  
...  
Keyword(s):  
Optic Neuritis ◽  
Plasma Exchange ◽  
Neuromyelitis Optica ◽  
Therapeutic Efficacy ◽  
Demyelinating Disease ◽  
High Risk Group ◽  
Functional Improvement ◽  
High Dose ◽  
Humoral Immune

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) with a poor prognosis in terms of the optic-spinal function. Recently, a serum autoantibody (NMO-IgG) binding to the blood–brain barrier region was detected exclusively in patients with NMO and its high risk group. We treated six NMO-IgG-positive patients (all female; age 21–67 years old, median 41; three with optic neuritis and three with myelitis) who were unresponsive to high-dose intravenous methylprednisolone (HIMP), with plasma exchange (PE) (three to five exchanges, 2–3 L each). Three of the patients(one with optic neuritis and two with myelitis) showed definite functional improvement following PE. The clinical improvement started to appear after one or two exchanges, while there was little or no improvement in the other three patients. Such quick clinical responses to PE suggest a pathogenetic role of humoral immune factors in NMO, although delayed responses to the corticosteroid therapy might have contributed to the therapeutic efficacy, in part. Further clinical and in vitro studies are needed to determine whether the removal of NMO-IgG is directly relevant to the therapeutic efficacy. PE may hasten the functional recovery from corticosteroid-resistant relapses in some NMO-IgG-positive patients with NMO.

Fulminant Acute Disseminated Encephalomyelitis: A Remarkable Outcome with Cyclophosphamide

2020 ◽  
Author(s):  
Hadas Meirson ◽  
Shelly I. Shiran ◽  
Michal Raz ◽  
Jonathan Roth ◽  
Aviva Fattal-Valevski
Keyword(s):  
Central Nervous System ◽  
Acute Treatment ◽  
Demyelinating Disease ◽  
Pediatric Population ◽  
Acute Disseminated Encephalomyelitis ◽  
High Dose ◽  
Cyclophosphamide Treatment ◽  
The Central Nervous System ◽  
Intravenous Glucocorticoids ◽  
Cyclophosphamide Administration

AbstractAcute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system which occurs predominantly in the pediatric population. Acute treatment is high-dose intravenous glucocorticoids. Alternative treatment is usually intravenous immune globulin and/or plasma exchange. Fulminant ADEM is rare in children. Only a few cases of cyclophosphamide use in refractory ADEM have been reported. Here, we report a case of a 12-year-old girl with fulminant ADEM who was comatose and improved dramatically after cyclophosphamide administration. Cyclophosphamide treatment should be considered as a therapy in children with fulminant ADEM nonresponsive to standard therapies.

scholarly journals Neuroprotective Effect of Schisandra Chinensis on Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonian Syndrome in C57BL/6 Mice

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1671 ◽  
Author(s):  
Chi-Lin Li ◽  
Yang-Hwei Tsuang ◽  
Tung-Hu Tsai
Keyword(s):  
Tyrosine Hydroxylase ◽  
Motor Coordination ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Parkinsonian Syndrome ◽  
Drug Candidate ◽  
High Dose ◽  
Dopamine Level ◽  
Schisandra Chinensis ◽  
Fruit Extract

Schisandra chinensis (Turcz.) Baill. (S. chinensis) is a well-known botanical medicine and nutritional supplement that has been shown to have potential effects on neurodegeneration. To investigate the potential neuroprotective effect of S. chinensis fruit extract, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce behavioral disorders and dopaminergic neuronal damage in mice, and biochemical indicators were examined. Male C57BL/6 mice were used to establish the MPTP-induced parkinsonian syndrome model. Open field and rotarod tests were performed to evaluate the overall manifestation of motor deficits and rodent motor coordination. The mice were divided into 8 groups as follows: normal control; MPTP alone (25 mg/kg, i.p.); S. chinensis extract pretreatment (0.5, 1.5, 5 g/kg, p.o.); and S. chinensis extract treatment (0.5, 1.5, 5 g/kg, p.o.). Liquid chromatography coupled to electrochemical detection was used to monitor neurochemicals in the striatum. Tyrosine hydroxylase content was measured by immunohistochemistry, and biochemical antioxidative indicators were used to evaluate the potential neuroprotective effects of S. chinensis fruit extract. The results demonstrated that treatment with S. chinensis fruit extract ameliorated MPTP-induced deficits in behavior, exercise balance, dopamine level, dopaminergic neurons, and tyrosine hydroxylase-positive cells in the striatum of mice. Among the pretreated and treatment groups, a high dose of S. chinensis fruit extract was the most effective treatment. In conclusion, S. chinensis fruit extract is a potential herbal drug candidate for the amelioration and prevention of Parkinson’s disease.

scholarly journals Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Jun-liang Yuan ◽  
Shuang-kun Wang ◽  
Xiao-juan Guo ◽  
Wen-li Hu
Keyword(s):  
Hepatitis B ◽  
Marked Improvement ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Acute Disseminated Encephalomyelitis ◽  
Hepatitis B Vaccination ◽  
High Dose ◽  
The Central Nervous System ◽  
Alteration Of Consciousness ◽  
Brain And Spinal Cord

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.

Optic Neuritis During Lactation: A Case Series

2020 ◽  
pp. 089033442097049
Author(s):  
Johnson Jeslin ◽  
C. Seetharaman ◽  
Virna M. Shah
Keyword(s):  
Optic Neuritis ◽  
Demyelinating Disease ◽  
Case Series ◽  
Rare Condition ◽  
Complete Recovery ◽  
High Dose ◽  
Oral Steroids ◽  
Optic Neuritis Treatment Trial ◽  
Intravenous Steroids ◽  
Sudden Blindness

Background Optic neuritis is a rare condition that can lead to sudden blindness and also could be a precursor to multiple sclerosis. When it occurs postpartum during lactation, it is called lactation optic neuritis. Main issue We present four cases of optic neuritis in lactating mothers, two of which had additional features of demyelinating disease upon neurological imaging. Management All participants were treated with high dose intravenous steroids followed by 11 days of oral steroids, per the optic neuritis treatment trial, which led to complete recovery of vision. Two participants with demyelinating disease on magnetic resonance imaging scans were advised to wean, because of a need for immunosuppressive therapy later. Conclusion Optic neuritis during lactation should be suspected following acute loss of vision. Prompt referral to an ophthalmologist is mandated for early diagnosis and treatment to prevent long-term co-morbidities.

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