Fingolimod (FTY720) improves the functional recovery and myelin preservation of the optic pathway in focal demyelination model of rat optic chiasm

Hashemian, Mona; Ghasemi-Kasman, Maryam; Parsian, Hadi; Sadeghi, Farzin

doi:10.1016/j.brainresbull.2019.08.014

Cited by 17 publications

(15 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In brief, animals were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg) and fixed in stereotaxic instrument (Stoelting, USA). LPC (1%, 2 µL) was injected into the optic chiasm using a Hamilton syringe (Coordinates: AP and ML: 0 from bregma and DV =−7.4 mm from dura surface) 36,40. LPC was injected within 2 min and the needle was kept in for an additional 3 min to avoid possible backflow through the needle tract.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

<p>Co-administration of aspirin and adipose-derived stem cell conditioned medium improves the functional recovery of the optic pathway in a lysolecithin-induced demyelination model</p>

Galeshi

Ghasemi-Kasman

Feizi

et al. 2019

NDT

Self Cite

View full text Add to dashboard Cite

Introduction: Based on beneficial effects of aspirin and mesenchymal stem cells (MSCs) on myelin repair, in a preset study, effects of co-administration of aspirin and conditioned medium from adipose tissue-derived stem cells (ADSC-CM) on functional recovery of optic pathway, demyelination levels, and astrocytes' activation were evaluated in a lysolecithin (LPC)-induced demyelination model of optic chiasm. Methods: LPC (1%, 2 µL) was injected into the rat optic chiasm and animals underwent daily intraperitoneal (i.p.) injections of ADSCs-CM and oral gavage of aspirin at a dose of 25 mg/kg for 14 days post LPC injection. The conductivity of visual signals was assessed using visual evoked potential recordings (VEPs) before LPC injection and on days 7 and 14 post lesion. Immunostaining against PDGFRα as oligodendrocyte precursor cells marker, MOG as mature myelin marker, and GFAP as astrocyte marker was performed on brain sections at day 14 post LPC injection. FluoroMyelin staining was also used to measure the extent of demyelination areas. Results: Our results showed that administration of ADSCs-CM and aspirin significantly reduced the latency of VEP waves in LPC receiving animals. In addition, demyelination levels and GFAP expressing cells were attenuated while the number of oligodendrocyte precursor cells significantly increased in rats treated with ADSCs-CM and aspirin. Conclusion: Overall, our results suggest that co-administration of ADSCs-CM and aspirin improves the functional recovery of optic pathway through amelioration of astrocyte activation and attenuation of demyelination level.

show abstract

Section: Methodsmentioning

confidence: 99%

“…The number of GFAP or PDGRα positive cells were counted using Image J software (version 1.42 V, NIH, USA). To analyze the immunostaining results, 3 sections from each slide and 3 slides from each animal and 3 rats were used for each group 40,41…”

Section: Methodsmentioning

confidence: 99%

<p>Co-administration of aspirin and adipose-derived stem cell conditioned medium improves the functional recovery of the optic pathway in a lysolecithin-induced demyelination model</p>

Galeshi

Ghasemi-Kasman

Feizi

et al. 2019

NDT

Self Cite

View full text Add to dashboard Cite

show abstract

“…Other intrinsic regenerative genes and pathways include Wnt signaling [114], Lin28 [115], Sry-related high-mobility-box 11 [116], Krüppel-like factor 4/9 [117], histone deacetylase [118], c-myc [119], and cAMP [93,120]. However, a single manipulation of these pathways or these genes is not enough for promoting long-lasting optic nerve regeneration in vivo.…”

Section: Intrinsic Survival and Regenerative Pathways For Optic Nerve Regenerationmentioning

confidence: 99%

The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina

Oshitari

2021

IJMS

View full text Add to dashboard Cite

Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina.

show abstract

“…Interaction with HDACs may have direct consequences in neurodegenerative and related conditions through modification of activated microglia phenotypes [43,44]. FTY720 shows protective activity in demyelination and blood-brain barrier (BBB) damage [44][45][46]. Moreover, fingolimod has also been suggested to exhibit (possibly selective) antibacterial properties, which might contribute to its efficiency in BBB and neuronal protection [47].…”

Section: Introductionmentioning

confidence: 99%

Fingolimod Affects Transcription of Genes Encoding Enzymes of Ceramide Metabolism in Animal Model of Alzheimer’s Disease

et al. 2020

View full text Add to dashboard Cite

The imbalance in sphingolipid signaling may be critically linked to the upstream events in the neurodegenerative cascade of Alzheimer's disease (AD). We analyzed the influence of mutant (V717I) amyloid β precursor protein (AβPP) transgene on sphingolipid metabolism enzymes in mouse hippocampus. At 3 months of age AβPP/Aβ presence upregulated enzymes of ceramide turnover on the salvage pathway: ceramide synthases (CERS2, CERS4, CERS6) and also ceramidase ACER3. At 6 months, only CERS6 was elevated, and no ceramide synthase was increased at 12 months. However, sphingomyelin synthases, which utilize ceramide on the sphingomyelinase pathway, were reduced (SGMS1 at 12 and SGMS2 at 6 months). mRNAs for sphingomyelin synthases SGMS1 and SGMS2 were also significantly downregulated in human AD hippocampus and neocortex when compared with age-matched controls. Our findings suggest early-phase deregulation of sphingolipid homeostasis in favor of ceramide signaling. Fingolimod (FTY720), a modulator of sphingosine-1-phosphate receptors countered the AβPP-dependent upregulation of hippocampal ceramide synthase CERS2 at 3 months. Moreover, at 12 months, FTY720 increased enzymes of ceramide-sphingosine turnover: CERS4, ASAH1, and ACER3. We also observed influence of fingolimod on the expression of the sphingomyelinase pathway enzymes. FTY720 counteracted the AβPP-linked reduction of sphingomyelin synthases SGMS1/2 (at 12 and 6 months, respectively) and led to elevation of sphingomyelinase SMPD2 (at 6 and 12 months). Therefore, our results demonstrate potentially beneficial, age-specific effects of fingolimod on transcription of sphingolipid metabolism enzymes in an animal model of AD.

show abstract

Fingolimod (FTY720) improves the functional recovery and myelin preservation of the optic pathway in focal demyelination model of rat optic chiasm

Cited by 17 publications

References 63 publications

<p>Co-administration of aspirin and adipose-derived stem cell conditioned medium improves the functional recovery of the optic pathway in a lysolecithin-induced demyelination model</p>

<p>Co-administration of aspirin and adipose-derived stem cell conditioned medium improves the functional recovery of the optic pathway in a lysolecithin-induced demyelination model</p>

The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina

Fingolimod Affects Transcription of Genes Encoding Enzymes of Ceramide Metabolism in Animal Model of Alzheimer’s Disease

Contact Info

Product

Resources

About