The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Mohammad Javan - One of the best experts on this subject based on the ideXlab platform.
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inactivation of sphingosine 1 phosphate receptor 2 s1pr2 decreases deMyelination and enhances reMyelination in animal models of multiple sclerosis
Neurobiology of Disease, 2019Co-Authors: Maryam S Seyedsadr, Ana Amorim, Matteo Egger, Javad Mirnajafizadeh, Mohammad Javan, Oliver Weinmann, Benjamin V. Ineichen, Burkhard Becher, Martin E. SchwabAbstract:Abstract Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) in which multiple sites of blood-brain barrier (BBB) disruption, focal inflammation, deMyelination and tissue destruction are the hallmarks. Here we show that sphingosine-1-phosphate receptor 2 (S1PR2) has a negative role in Myelin Repair as well as an important role in deMyelination by modulating BBB permeability. In lysolecithin-induced deMyelination of adult mouse spinal cord, S1PR2 inactivation by either the pharmacological inhibitor JTE-013 or S1PR2 gene knockout led to enhanced Myelin Repair as determined by higher numbers of differentiated oligodendrocytes and increased numbers of reMyelinated axons at the lesion sites. S1PR2 inactivation in lysolecithin-induced deMyelination of the optic chiasm, enhanced oligodendrogenesis and improved the behavioral outcome in an optokinetic reflex test. In order to see the effect of S1PR2 inactivation on deMyelination, experimental autoimmune encephalitis (EAE) was induced by MOG-peptide. S1PR2 inhibition or knockout decreased the extent of deMyelinated areas as well as the clinical disability in this EAE model. Both toxin induced and EAE models showed decreased BBB leakage and reduced numbers of Iba1+ macrophages following S1PR2 inactivation. Our results suggest that S1PR2 activity impairs reMyelination and also enhances BBB leakage and deMyelination. The former effect could be mediated by Nogo-A, as antagonism of this factor enhances reMyelination and S1PR2 can act as a Nogo-A receptor.
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fingolimod enhances Myelin Repair of hippocampus in pentylenetetrazol induced kindling model
European Journal of Pharmaceutical Sciences, 2017Co-Authors: Davoud Ghorbanian, Javad Mirnajafizadeh, Mohammad Javan, Samaneh Hassanzadeh, Maryam GhasemikasmanAbstract:Abstract Recent evidence indicates that deMyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and Myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert Myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1 mg/kg dosage of FTY720, 1 h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i.p. once daily for 7 consecutive days. Treatment with FTY720 (especially lower dose) reduced the frequency of seizures and epileptiform discharges in both approaches. We found that FTY720 administration decreases cell death and glial activation in CA1 and CA3 regions of hippocampus. Myelin protection effect was shown by increasing Myelin levels. Furthermore, post-treatment of FTY720 enhanced endogenous reMyelination and the number of oligodendrocyte precursor cells in fully kindled animals. Together, these results demonstrate that FTY720 behind the anti-inflammatory and neuroprotection effects has beneficial role in Myelin protection and reMyelination enhancement in PTZ kindling model of seizure and it may be provide a new therapeutic option for deMyelination associated with epilepsy.
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polymerized nano curcumin attenuates neurological symptoms in eae model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and Myelin Repair
Neuropharmacology, 2015Co-Authors: Maryam Mohajeri, Majid Sadeghizadeh, Farhood Najafi, Mohammad JavanAbstract:Multiple Sclerosis (MS) is an inflammatory deMyelinating disorder of central nervous system (CNS). Polyphenol curcumin has been used in traditional medicine as an effective drug for a variety of diseases. Different formulations of curcumin are introduced to increase its stability and effectiveness. Here we have examined the effect of polymerized form of nano-curcumin (PNC) on experimental autoimmune encephalomyelitis (EAE) as an animal model of MS. EAE was induced in female Lewis rats and PNC or curcumin was daily administrated intraperitonealy from day 12-29 post immunization. When the prophylactic effect of PNC was under investigation, rats received PNC from the first day of immunization. Treatment with PNC resulted in decreased scores of disease in therapeutic and prophylactic administration when compared with control group. Staining by luxol fast blue and H&E and immuno-staining of lumbar spinal cord cross sections, confirmed a significant decrease in the amounts of deMyelination, inflammation and BBB breaking down. Gene expression studies in lumbar spinal cord showed a corrected balance of pro-inflammatory and anti-inflammatory genes expression, decreased oxidative stress, improved reMyelination and increased progenitor cell markers after treatment with PNC. Our results demonstrated an efficient therapeutic effect of PNC as an anti-inflammatory and anti-oxidative stress agent, with significant effects on the EAE scores and Myelin Repair mechanisms.
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analysis of structural and molecular events associated with adult rat optic chiasm and nerves deMyelination and reMyelination possible role for 3rd ventricle proliferating cells
Neuromolecular Medicine, 2011Co-Authors: Sabah Mozafari, Mohammad Amin Sherafat, Motahareh Heibatollahi, Shahram Pourbeiranvand, Taki Tiraihi, Javad Mirnajafizadeh, Mohammad Javan, Abolhasan AhmadianiAbstract:Multiple sclerosis frequently affects the optic apparatus, particularly optic chiasm and nerves. Here, we have reported the structural and molecular characteristics of reMyelination in the adult rat optic chiasm and nerves. Moreover, considering the proximity of optic chiasm and 3rd ventricle, we have tried to determine if proliferating cells residing in 3rd ventricle region are able to migrate in response to experimental deMyelination of the optic chiasm. Following local deMyelination by lysolecithin, reMyelination pattern in longitude of optic chiasm and proximal nerves was investigated using Myelin staining and marker genes expression. Furthermore, cell tracing was carried out using BrdU labeling of proliferating cells prior to gliotoxin injection. Morphometric analysis revealed that deMyelination was considerable on days 7 and 14 and an incomplete reMyelination occurred on day 28 post-lesion. Interestingly, Myelin Repair was more evident in the caudal part of chiasm, compared to rostral part and proximal optic nerves. Following chiasm and nerve deMyelination, trains of BrdU+ cells were seen near the 3rd ventricle which subsequently moved to lesion site. Nestin was significantly up-regulated in 3rd ventricle surroundings. At the lesion site, Nogo-A gene expression was significantly decreased on days 7 and 14 post lesion, while Olig2, nestin, and GFAP expression was increased on day 7. The changes were then reversed by the time. Myelin Repair in optic chiasm seems to be mediated by endogenous progenitors and stem cells. Adult 3rd ventricle proliferating cells may play a role in this context by mobilization into the deMyelinated chiasm.
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visual evoked potentials and mbp gene expression imply endogenous Myelin Repair in adult rat optic nerve and chiasm following local lysolecithin induced deMyelination
Brain Research, 2010Co-Authors: Sabah Mozafari, Mohammad Amin Sherafat, Javad Mirnajafizadeh, Mohammad Javan, Taki TiraihiAbstract:Abstract Multiple sclerosis (MS) patients may suffer from optic disturbances. Toxin-induced deMyelinations have frequently been developed to investigate the cellular and structural aspects of deMyelination and reMyelination processes, separately. The present study describes functional consequence of lysolecithin (LPC)-induced lesion in the adult rat optic nerves and chiasm by recording the visual evoked potentials (VEPs) from the visual cortex and its correlation with Myelin basic protein (MBP) expression in lesion site. Records of VEP were obtained at 2, 7, 14 and 28 days post-injection. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and latency after the lesion as well as in comparison with those generated in control animals. These observations were confirmed through measurement of mRNA expression level for MBP which is one of the important genes expressed in mature oligodendrocytes and Schwann cells. The level of MBP mRNAs in deMyelinated chiasm and optic nerves decreased following lysolecithin injection with its least value on day 7, and then it increased to the control level 14 days post-lesion. However, it continued to increase even after that and reached a maximum level 28 days post lesion. Results of the present paper show that, LPC injection in the chiasm share functional and molecular alterations which are found in deMyelinating disorders in both the optic nerves and chiasm and also these alterations were coming back to level of control animal on 28 days post lesion, which is typically seen in Myelin Repair process. The present paper provides new insights into the experimental toxin-induced models that may be useful for evaluating the functional recovery of deMyelinated optic nerves and chiasm following various Repairing strategies. It also seems to be useful for studying the protective or reMyelinating effects of different therapies in e.g. optic apparatus which is more affected by MS.
Javad Mirnajafizadeh - One of the best experts on this subject based on the ideXlab platform.
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inactivation of sphingosine 1 phosphate receptor 2 s1pr2 decreases deMyelination and enhances reMyelination in animal models of multiple sclerosis
Neurobiology of Disease, 2019Co-Authors: Maryam S Seyedsadr, Ana Amorim, Matteo Egger, Javad Mirnajafizadeh, Mohammad Javan, Oliver Weinmann, Benjamin V. Ineichen, Burkhard Becher, Martin E. SchwabAbstract:Abstract Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) in which multiple sites of blood-brain barrier (BBB) disruption, focal inflammation, deMyelination and tissue destruction are the hallmarks. Here we show that sphingosine-1-phosphate receptor 2 (S1PR2) has a negative role in Myelin Repair as well as an important role in deMyelination by modulating BBB permeability. In lysolecithin-induced deMyelination of adult mouse spinal cord, S1PR2 inactivation by either the pharmacological inhibitor JTE-013 or S1PR2 gene knockout led to enhanced Myelin Repair as determined by higher numbers of differentiated oligodendrocytes and increased numbers of reMyelinated axons at the lesion sites. S1PR2 inactivation in lysolecithin-induced deMyelination of the optic chiasm, enhanced oligodendrogenesis and improved the behavioral outcome in an optokinetic reflex test. In order to see the effect of S1PR2 inactivation on deMyelination, experimental autoimmune encephalitis (EAE) was induced by MOG-peptide. S1PR2 inhibition or knockout decreased the extent of deMyelinated areas as well as the clinical disability in this EAE model. Both toxin induced and EAE models showed decreased BBB leakage and reduced numbers of Iba1+ macrophages following S1PR2 inactivation. Our results suggest that S1PR2 activity impairs reMyelination and also enhances BBB leakage and deMyelination. The former effect could be mediated by Nogo-A, as antagonism of this factor enhances reMyelination and S1PR2 can act as a Nogo-A receptor.
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fingolimod enhances Myelin Repair of hippocampus in pentylenetetrazol induced kindling model
European Journal of Pharmaceutical Sciences, 2017Co-Authors: Davoud Ghorbanian, Javad Mirnajafizadeh, Mohammad Javan, Samaneh Hassanzadeh, Maryam GhasemikasmanAbstract:Abstract Recent evidence indicates that deMyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and Myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert Myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1 mg/kg dosage of FTY720, 1 h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i.p. once daily for 7 consecutive days. Treatment with FTY720 (especially lower dose) reduced the frequency of seizures and epileptiform discharges in both approaches. We found that FTY720 administration decreases cell death and glial activation in CA1 and CA3 regions of hippocampus. Myelin protection effect was shown by increasing Myelin levels. Furthermore, post-treatment of FTY720 enhanced endogenous reMyelination and the number of oligodendrocyte precursor cells in fully kindled animals. Together, these results demonstrate that FTY720 behind the anti-inflammatory and neuroprotection effects has beneficial role in Myelin protection and reMyelination enhancement in PTZ kindling model of seizure and it may be provide a new therapeutic option for deMyelination associated with epilepsy.
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oct4 transcription factor in conjunction with valproic acid accelerates Myelin Repair in deMyelinated optic chiasm in mice
Neuroscience, 2016Co-Authors: Samaneh Dehghan, Javad Mirnajafizadeh, M Hesaraki, Masoud Soleimani, Yaghoub Fathollahi, Mohamad JavanAbstract:Abstract Multiple sclerosis is a deMyelinating disease with severe neurological symptoms due to blockage of signal conduction in affected axons. Spontaneous reMyelination via endogenous progenitors is limited and eventually fails. Recent reports showed that forced expression of some transcription factors within the brain converted somatic cells to neural progenitors and neuroblasts. Here, we report the effect of valproic acid (VPA) along with forced expression of Oct4 transcription factor on lysolecithin (LPC)-induced experimental deMyelination. Mice were gavaged with VPA for one week, and then inducible Oct4 expressing lentiviral particles were injected into the lateral ventricle. After one-week induction of Oct4, LPC was injected into the optic chiasm. Functional reMyelination was assessed by visual-evoked potential (VEP) recording. Myelination level was studied using FluoroMyelin staining and immunohistofluorescent (IHF) against proteolipid protein (PLP). IHF was also performed to detect Oct4 and SSEA1 as pluripotency markers and Olig2, Sox10, CNPase and PDGFRα as oligodendrocyte lineage markers. One week after injection of Oct4 expressing vector, pluripotency markers SSEA1 and Oct4 were detected in the rims of the 3rd ventricle. LPC injection caused extensive deMyelination and significantly delayed the latency of VEP wave. Animals pre-treated with VPA + Oct4 expressing vector, showed faster recovery in the VEP latency and enhanced Myelination. Immunostaining against oligodendrocyte lineage markers showed an increased number of Sox10+ and Myelinating cells. Moreover, transdifferentiation of some Oct4-transfected cells (GFP+ cells) to Olig2+ and CNPase+ cells was confirmed by immunostaining. One-week administration of VPA followed by one-week forced expression of Oct4 enhanced Myelination by converting transduced cells to Myelinating oligodendrocytes. This finding seems promising for enhancing Myelin Repair within the adult brains.
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analysis of structural and molecular events associated with adult rat optic chiasm and nerves deMyelination and reMyelination possible role for 3rd ventricle proliferating cells
Neuromolecular Medicine, 2011Co-Authors: Sabah Mozafari, Mohammad Amin Sherafat, Motahareh Heibatollahi, Shahram Pourbeiranvand, Taki Tiraihi, Javad Mirnajafizadeh, Mohammad Javan, Abolhasan AhmadianiAbstract:Multiple sclerosis frequently affects the optic apparatus, particularly optic chiasm and nerves. Here, we have reported the structural and molecular characteristics of reMyelination in the adult rat optic chiasm and nerves. Moreover, considering the proximity of optic chiasm and 3rd ventricle, we have tried to determine if proliferating cells residing in 3rd ventricle region are able to migrate in response to experimental deMyelination of the optic chiasm. Following local deMyelination by lysolecithin, reMyelination pattern in longitude of optic chiasm and proximal nerves was investigated using Myelin staining and marker genes expression. Furthermore, cell tracing was carried out using BrdU labeling of proliferating cells prior to gliotoxin injection. Morphometric analysis revealed that deMyelination was considerable on days 7 and 14 and an incomplete reMyelination occurred on day 28 post-lesion. Interestingly, Myelin Repair was more evident in the caudal part of chiasm, compared to rostral part and proximal optic nerves. Following chiasm and nerve deMyelination, trains of BrdU+ cells were seen near the 3rd ventricle which subsequently moved to lesion site. Nestin was significantly up-regulated in 3rd ventricle surroundings. At the lesion site, Nogo-A gene expression was significantly decreased on days 7 and 14 post lesion, while Olig2, nestin, and GFAP expression was increased on day 7. The changes were then reversed by the time. Myelin Repair in optic chiasm seems to be mediated by endogenous progenitors and stem cells. Adult 3rd ventricle proliferating cells may play a role in this context by mobilization into the deMyelinated chiasm.
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visual evoked potentials and mbp gene expression imply endogenous Myelin Repair in adult rat optic nerve and chiasm following local lysolecithin induced deMyelination
Brain Research, 2010Co-Authors: Sabah Mozafari, Mohammad Amin Sherafat, Javad Mirnajafizadeh, Mohammad Javan, Taki TiraihiAbstract:Abstract Multiple sclerosis (MS) patients may suffer from optic disturbances. Toxin-induced deMyelinations have frequently been developed to investigate the cellular and structural aspects of deMyelination and reMyelination processes, separately. The present study describes functional consequence of lysolecithin (LPC)-induced lesion in the adult rat optic nerves and chiasm by recording the visual evoked potentials (VEPs) from the visual cortex and its correlation with Myelin basic protein (MBP) expression in lesion site. Records of VEP were obtained at 2, 7, 14 and 28 days post-injection. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and latency after the lesion as well as in comparison with those generated in control animals. These observations were confirmed through measurement of mRNA expression level for MBP which is one of the important genes expressed in mature oligodendrocytes and Schwann cells. The level of MBP mRNAs in deMyelinated chiasm and optic nerves decreased following lysolecithin injection with its least value on day 7, and then it increased to the control level 14 days post-lesion. However, it continued to increase even after that and reached a maximum level 28 days post lesion. Results of the present paper show that, LPC injection in the chiasm share functional and molecular alterations which are found in deMyelinating disorders in both the optic nerves and chiasm and also these alterations were coming back to level of control animal on 28 days post lesion, which is typically seen in Myelin Repair process. The present paper provides new insights into the experimental toxin-induced models that may be useful for evaluating the functional recovery of deMyelinated optic nerves and chiasm following various Repairing strategies. It also seems to be useful for studying the protective or reMyelinating effects of different therapies in e.g. optic apparatus which is more affected by MS.
Holly S. Cate - One of the best experts on this subject based on the ideXlab platform.
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investigation of sequential growth factor delivery during cuprizone challenge in mice aimed to enhance oligodendrogliogenesis and Myelin Repair
PLOS ONE, 2013Co-Authors: Jennifer K Sabo, Tim D Aumann, Trevor J Kilpatrick, Holly S. CateAbstract:Repair in multiple sclerosis involves reMyelination, a process in which axons are provided with a new Myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs) are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs) in vivo during deMyelination and reMyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced deMyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and reMyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1) promotes the survival of OPCs during cuprizone-induced deMyelination. Based on these data, we investigated whether Myelin Repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter reMyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average Myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of deMyelination, only Noggin infusion promoted reMyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance Myelin Repair above what occurs with delivery of Noggin alone.
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Signalling pathways that inhibit the capacity of precursor cells for Myelin Repair.
International journal of molecular sciences, 2013Co-Authors: Jennifer K Sabo, Holly S. CateAbstract:In deMyelinating disorders such as Multiple Sclerosis (MS), targets of injury are Myelin and oligodendrocytes, leading to severe neurological dysfunction. Regenerative therapies aimed at promoting oligodendrocyte maturation and reMyelination are promising strategies for treatment in deMyelinating disorders. Endogenous precursor cells or exogenous transplanted cells are potential sources for reMyelinating oligodendrocytes in the central nervous system (CNS). Several signalling pathways have been implicated in regulating the capacity of these cell populations for Myelin Repair. Here, we review neural precursor cells and oligodendrocyte progenitor cells as potential sources for reMyelinating oligodendrocytes and evidence for the functional role of key signalling pathways in inhibiting regeneration from these precursor cell populations.
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leukemia inhibitory factor signaling modulates both central nervous system deMyelination and Myelin Repair
Glia, 2008Co-Authors: Mark Marriott, Holly S. Cate, Ben Emery, Michele D Binder, Dennis Kemper, Scott C Kolbe, Ian Gordon, Hong Wang, Gary F Egan, Simon S MurrayAbstract:Leukemia inhibitory factor (LIF) receptor signaling limits the severity of inflammatory deMyelination in experimental autoimmune encephalomyelitis, a T-cell dependent animal model of multiple sclerosis (MS) [Butzkueven et al. (2002) Nat Med 8:613–619]. To identify whether LIF exerts direct effects within the central nervous system to limit deMyelination, we have studied the influence of LIF upon the phenotype of mice challenged with cuprizone, a copper chelator, which produces a toxic oligodendrocytopathy. We find that exogenously administered LIF limits cuprizone-induced deMyelination. Knockout mice deficient in LIF exhibit both potentiated deMyelination and oligodendrocyte loss after cuprizone challenge, an effect that is ameliorated by exogenous LIF, arguing for a direct beneficial effect of endogenous LIF receptor signaling. Numbers of oligodendrocyte progenitor cells in cuprizone-challenged mice are not influenced by either exogenous LIF or LIF deficiency, arguing for effects directed to the differentiated oligodendrocyte. Studies on the influence of LIF upon reMyelination after cuprizone challenge fail to reveal any significant effect of exogenous LIF. The LIF-knockout mice do, however, display impaired reMyelination, although oligodendrocyte replenishment, previously identified to occur from the progenitor pool, is not significantly compromised. Thus endogenous LIF receptor signaling is not only protective of oligodendrocytes but can also enhance reMyelination, and exogenous LIF has therapeutic potential in limiting the consequences of oligodendrocyte damage. © 2008 Wiley-Liss, Inc.
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leukemia inhibitory factor signaling modulates both central nervous system deMyelination and Myelin Repair
Glia, 2008Co-Authors: Mark Marriott, Holly S. Cate, Ben Emery, Michele D Binder, Dennis Kemper, Scott C Kolbe, Ian Gordon, Hong Wang, Gary F Egan, Simon S MurrayAbstract:Leukemia inhibitory factor (LIF) receptor signaling limits the severity of inflammatory deMyelination in experimental autoimmune encephalomyelitis, a T-cell dependent animal model of multiple sclerosis (MS) [Butzkueven et al. (2002) Nat Med 8:613-619]. To identify whether LIF exerts direct effects within the central nervous system to limit deMyelination, we have studied the influence of LIF upon the phenotype of mice challenged with cuprizone, a copper chelator, which produces a toxic oligodendrocytopathy. We find that exogenously administered LIF limits cuprizone-induced deMyelination. Knockout mice deficient in LIF exhibit both potentiated deMyelination and oligodendrocyte loss after cuprizone challenge, an effect that is ameliorated by exogenous LIF, arguing for a direct beneficial effect of endogenous LIF receptor signaling. Numbers of oligodendrocyte progenitor cells in cuprizone-challenged mice are not influenced by either exogenous LIF or LIF deficiency, arguing for effects directed to the differentiated oligodendrocyte. Studies on the influence of LIF upon reMyelination after cuprizone challenge fail to reveal any significant effect of exogenous LIF. The LIF-knockout mice do, however, display impaired reMyelination, although oligodendrocyte replenishment, previously identified to occur from the progenitor pool, is not significantly compromised. Thus endogenous LIF receptor signaling is not only protective of oligodendrocytes but can also enhance reMyelination, and exogenous LIF has therapeutic potential in limiting the consequences of oligodendrocyte damage.
Maryam Ghasemikasman - One of the best experts on this subject based on the ideXlab platform.
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direct conversion of somatic cells towards oligodendroglial lineage cells a novel strategy for enhancement of Myelin Repair
Journal of Cellular Physiology, 2020Co-Authors: Hanie Yavarpourbali, Maryam Nakhaeinejad, Azadeh Yazdi, Maryam GhasemikasmanAbstract:Oligodendrocyte precursor cells (OPCs) are considered as the main cell source for Myelination in the central nervous system. Following deMyelination, proliferation, migration, and differentiation capability of endogenous OPCs remarkably increase leading to reMyelination in damaged areas. Despite the beneficial impacts of resident OPCs for Myelin Repair, the capacity of endogenous Repair is low and insufficient. Therefore, several strategies have been developed to improve endogenous Myelin Repair. Although stem cell therapy has been introduced as a promising strategy for neurodegenerative disorders, but several limitations such as cell rejection, teratoma formation, and ethical concerns have hampered the extensive application of stem cells in clinic. In recent years, direct conversion of fully differentiated somatic cells into desired cells in the lesion area has opened a new era in regenerative medicine. In addition to direct reprogramming of somatic cells to neurons, recent evidence have also demonstrated that somatic cells, including fibroblasts and astrocytes, can be directly reprogrammed to OPC-like cells by overexpression of some specific transcription factors, microRNAs, or application of small molecules. Interestingly, induced OPCs differentiated to Myelinating oligodendrocytes that could effectively ensheath the host axons. In the present review article, the current advancements in direct conversion of somatic cells towards oligodendroglial cells have been discussed both in vitro and in vivo.
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querectin improves Myelin Repair of optic chiasm in lyolecithin induced focal deMyelination model
Biomedicine & Pharmacotherapy, 2018Co-Authors: Reza Naeimi, Ali Akbar Moghadamnia, Saeideh Baradaran, Manouchehr Ashrafpour, Maryam GhasemikasmanAbstract:Abstract Although the beneficial effects of quercetin on oligodendrocyte precursor cell (OPCs) population has been evaluated in-vitro, there are few studies about the effects of quercetin on Myelin Repair in the context of deMyelination. The aim of this study was to investigate the effects of querectin on functional recovery and Myelin Repair of optic chiasm in lysolecithin (LPC)-induced deMyelination model. DeMyelination was induced by local injection of LPC 1% (2 μl) into rat optic chiasm. Querectin at doses 25 or 50 mg/kg was administrated daily by oral gavage for 7 or 14 days post LPC. Visual evoked potential (VEPs) recordings were used to assess the functional property of the optic pathway. Immunostaining and Myelin staining were performed on brain sections 7 or 14 days post lesion. Electrophysiological data indicated that LPC injection increased the latency of VEPs waves and quercetin effectively reduced the delay of visual signals. The level of glial activation was alleviated in animals under treatment of quercetin compared to vehicle group. Furthermore, quercetin treatment decreased the extent of deMyelination areas and increased the reMyelination process following LPC injection. Overall, our findings indicate that quercetin could remarkably improve the functional recovery of the optic pathway by its protective effects on Myelin sheath and attenuation of glial activation.
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pregabalin enhances Myelin Repair and attenuates glial activation in lysolecithin induced deMyelination model of rat optic chiasm
Neuroscience, 2017Co-Authors: Danyal Daneshdoust, Davoud Ghorbanian, Maryam Ghasemikasman, Mohsen Khalilifomeshi, Mona Hashemian, Mohammad Gholami, Ali Akbar Moghadamnia, Amir ShojaeiAbstract:Multiple sclerosis (MS) is an autoimmune disease in which more than 70% of patients experience visual disturbance as the earliest symptoms. Lysolecithin (LPC)-induced focal deMyelination model has been developed to evaluate the effects of different therapies on Myelin Repair improvement. In this study, the effects of pregabalin administration on Myelin Repair and glial activation were investigated. Local deMyelination was induced by administration of LPC (1%, 2μL) into the rat optic chiasm. Rats underwent daily injection of pregabalin (30mg/kg, i.p) or vehicle. Visual-evoked potentials (VEPs) recordings were performed for evaluating the function of optic pathway on days 3, 7, 14 and 28 post lesions. Myelin specific staining and immunostaining against GFAP and Iba1 were also carried out for assessment of Myelination and glial activation respectively. Electrophysiological data indicated that pregabalin administration could significantly reduce the P1-N1 latency and increase the amplitude of VEPs waves compared to saline group. Luxol fast blue staining and immunostaining against PLP, as mature Myelin marker, showed that Myelin Repair was improved in animals received pregabalin treatment. In addition, pregabalin effectively reduced the expression of GFAP and Iba1 as activated glial markers in optic chiasm. The present study indicates that pregabalin administration enhances Myelin Repair and ameliorates glial activation of optic chiasm following local injection of LPC.
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fingolimod enhances Myelin Repair of hippocampus in pentylenetetrazol induced kindling model
European Journal of Pharmaceutical Sciences, 2017Co-Authors: Davoud Ghorbanian, Javad Mirnajafizadeh, Mohammad Javan, Samaneh Hassanzadeh, Maryam GhasemikasmanAbstract:Abstract Recent evidence indicates that deMyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and Myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert Myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1 mg/kg dosage of FTY720, 1 h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i.p. once daily for 7 consecutive days. Treatment with FTY720 (especially lower dose) reduced the frequency of seizures and epileptiform discharges in both approaches. We found that FTY720 administration decreases cell death and glial activation in CA1 and CA3 regions of hippocampus. Myelin protection effect was shown by increasing Myelin levels. Furthermore, post-treatment of FTY720 enhanced endogenous reMyelination and the number of oligodendrocyte precursor cells in fully kindled animals. Together, these results demonstrate that FTY720 behind the anti-inflammatory and neuroprotection effects has beneficial role in Myelin protection and reMyelination enhancement in PTZ kindling model of seizure and it may be provide a new therapeutic option for deMyelination associated with epilepsy.
Martin E. Schwab - One of the best experts on this subject based on the ideXlab platform.
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inactivation of sphingosine 1 phosphate receptor 2 s1pr2 decreases deMyelination and enhances reMyelination in animal models of multiple sclerosis
Neurobiology of Disease, 2019Co-Authors: Maryam S Seyedsadr, Ana Amorim, Matteo Egger, Javad Mirnajafizadeh, Mohammad Javan, Oliver Weinmann, Benjamin V. Ineichen, Burkhard Becher, Martin E. SchwabAbstract:Abstract Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) in which multiple sites of blood-brain barrier (BBB) disruption, focal inflammation, deMyelination and tissue destruction are the hallmarks. Here we show that sphingosine-1-phosphate receptor 2 (S1PR2) has a negative role in Myelin Repair as well as an important role in deMyelination by modulating BBB permeability. In lysolecithin-induced deMyelination of adult mouse spinal cord, S1PR2 inactivation by either the pharmacological inhibitor JTE-013 or S1PR2 gene knockout led to enhanced Myelin Repair as determined by higher numbers of differentiated oligodendrocytes and increased numbers of reMyelinated axons at the lesion sites. S1PR2 inactivation in lysolecithin-induced deMyelination of the optic chiasm, enhanced oligodendrogenesis and improved the behavioral outcome in an optokinetic reflex test. In order to see the effect of S1PR2 inactivation on deMyelination, experimental autoimmune encephalitis (EAE) was induced by MOG-peptide. S1PR2 inhibition or knockout decreased the extent of deMyelinated areas as well as the clinical disability in this EAE model. Both toxin induced and EAE models showed decreased BBB leakage and reduced numbers of Iba1+ macrophages following S1PR2 inactivation. Our results suggest that S1PR2 activity impairs reMyelination and also enhances BBB leakage and deMyelination. The former effect could be mediated by Nogo-A, as antagonism of this factor enhances reMyelination and S1PR2 can act as a Nogo-A receptor.
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intrathecal insulin like growth factor 1 but not insulin enhances Myelin Repair in young and aged rats
Neuroscience Letters, 2017Co-Authors: Martin Hlavica, Maryam S Seyedsadr, Martin E. Schwab, Nicolas Good, Patricia S Plattner, Aro Delparente, Andrin Good, Dianne P Figlewicz, Benjamin V. IneichenAbstract:One main pathological hallmark of multiple sclerosis (MS) is deMyelination. Novel therapies which enhance Myelin Repair are urgently needed. Insulin and insulin-like growth factor 1 (IGF-1) have strong functional relationships. Here, we addressed the potential capacity of IGF-1 and insulin to enhance reMyelination in an animal deMyelination model in vivo. We found that chronic intrathecal infusion of IGF-1 enhanced reMyelination after lysolecithin-induced deMyelination in the spinal cord of young and aged rats. Aged rats showed a weaker innate reMyelination capacity and are therefore a good model for progressive MS which is defined by chronic deMyelination. In contrast to IGF-1, Insulin had no effect on reMyelination in either age group. Our findings highlight the potential use of IGF-1 as reMyelinating therapy for MS, particularly the progressive stage in which chronic deMyelination is the hallmark.
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sudan black a fast easy and non toxic method to assess Myelin Repair in deMyelinating diseases
Neuropathology and Applied Neurobiology, 2017Co-Authors: Benjamin V. Ineichen, Oliver Weinmann, Nicolas Good, Patricia S Plattner, Carla A Wicki, Elisabeth J Rushing, Michael Linnebank, Martin E. SchwabAbstract:Aims The search for novel drugs that enhance Myelin Repair in entities such as multiple sclerosis has top priority in neurological research, not least because reMyelination can hinder further neurodegeneration in neuro-inflammatory conditions. Recently, several new compounds with the potential to boost reMyelination have been identified using high-throughput in vitro screening methods. However, assessing their potential to enhance reMyelination in vivo using plastic embedded semi-thin sections or electron microscopy, even though being the gold standard for assessing reMyelination, is toxic, extremely time-consuming, and expensive. Methods We screened available Myelin dyes for a staining candidate which offers a faster and easier alternative to visualize reMyelination in cryo-sections. Results We identified sudan black as a candidate with excellent Myelin resolution and we show that our adapted sudan black staining can demonstrate Myelin Repair in rodent spinal cord cryosections as reliable as in semithin sections, but much faster, easier, less toxic and less expensive. Besides that, it can resolve the small Myelinated axons in the corpus callosum. The staining can yet readily be combined with immunostainings which can be challenging in semithin sections. We validated the method in human spinal cord tissue as well as in experimental deMyelination of the rat spinal cord by a lysolecithin time course experiment. As proof-of-principle, we demonstrate that sudan black is able to reliably detect the reMyelination enhancing properties of benztropine. Conclusion Our adapted sudan black staining can be used to rapidly and non-toxically screen for reMyelinating therapies in deMyelinating diseases. This article is protected by copyright. All rights reserved.
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reactions of oligodendrocytes to spinal cord injury cell survival and Myelin Repair
Experimental Neurology, 2000Co-Authors: Eveline Frei, Isabel Klusman, Lisa Schnell, Martin E. SchwabAbstract:The aim of this study was to elucidate whether oligodendrocytes die in fiber tracts that are spared by a spinal cord injury but are in close vicinity of inflammatory cells. Adult rat spinal cords were studied histologically 1 day to 2 weeks after a contusion lesion that left the ventral white matter largely intact. Massive oligodendrocyte death occurred in the lesion center, along with the death of neurons, microglia, and astrocytes. Oligodendrocytes, specifically positive for proteolipid protein (PLP) mRNA, were counted in the ventral white matter where axons at the rostral and caudal edges of the lesion were histologically intact. Although these regions contained many macrophages and neutrophils hypothesized to contribute to secondary tissue loss, there was no significant loss of oligodendrocytes. In the ventral funiculus, 3 and 6 mm rostral and caudal to the lesion, oligodendrocyte numbers were also unchanged, in spite of the presence of many activated microglial cells. From day 7 on, oligodendrocytes in close vicinity to the lesion increased their expression of PLP mRNA. We conclude that, at least within the first 2 weeks after a spinal cord contusion lesion, there is no major devastating influence of inflammatory cells or their mediators on oligodendrocytes. When death occurs, it may be due to mechanical trauma, ischemia, or excitotoxicity within the lesion or it may occur as a result of axonal degeneration.
