Rat Model Of Multiple Sclerosis Research Articles

New Insight into the Possible Roles of L-Carnitine in a Rat Model of Multiple Sclerosis.

We investigated the effect of L-carnitine (LC) on cuprizone (Cup) demyelinating rat model and its possible underlying mechanisms. Thirty male Sprague-Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1β, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA. There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1β, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01). The current study demonstrates a neuroprotective effect of LC in a Cup-induced demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.

Effects of Levothyroxine on Behavior and Cognitive Decline in a Rat Model of Multiple Sclerosis: A Biochemical Study

Background: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system (CNS) that affects the development and physiological function of the brain and causes memory impairment. Objectives: Due to the anti-inflammatory and antioxidant role of levothyroxine (L-T4) on myelin production and adult cerebral function, this study aimed to evaluate the effects of L-T4 on the improvement of cognitive deficits and cerebral inflammation. Methods: Forty Wistar rats were randomly divided into five groups: (1) sham, (2) L-T4, (3) MS, (4) MS receiving L-T4, and (5) Betaferon. For MS induction, lysolecithin was injected into the CA1 of the hippocampus. Rats received L-T4 intraperitoneally at a dose of 100 μg/kg in the second and fourth groups. The shuttle box and Morris water maze tests were used to investigate passive avoidance and spatial memory, respectively. Also, the hippocampal concentrations of total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and c-reactive protein (CRP) were measured to investigate molecular changes. Results: Path length (P &lt; 0.001, P = 0.0015, and P = 0.002 on days 1 to 3, respectively) and latency time (P &lt; 0.001 on the second and third days) increased, but the speed of movements (P &lt; 0.001) and time spent in goal quarter decreased in MS-induced groups (P &lt; 0.001). Treatment with L-T4 for 14 days significantly reversed path length and speed (P &lt; 0.001 and P = 0.0315 on the second and third days), latency time (P &lt; 0.01), speed (P &lt; 0.001 and P = 0.0038 on the second and third days), and time spent in goal quarter (P = 0.1203) in the MS group. The hippocampal concentrations of MDA (P = 0.0010), TNF-α (P = 0.0251), and CRP (P = 0.0065) were significantly lower in the MS group treated with L-T4 than in the MS group. Also, the hippocampal concentration of TAC was significantly increased (P = 0.0375) in the MS group receiving L-T4. Conclusions: It seems that treatment with L-T4 can prevent cognitive impairment caused by MS induction. Ameliorative effects of L-T4 may be due to the reduction of inflammation and oxidative stress. Therefore, L-T4 can be used as an effective agent in the treatment of MS.

Glutamate transporter contribution to retinal ganglion cell vulnerability in a rat model of multiple sclerosis

Glial glutamate transporters actively participate in neurotransmission and have a fundamental role in determining the ambient glutamate concentration in the extracellular space. Their expression is dynamically regulated in many diseases, including experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In EAE, a downregulation has been reported which may render neurons more susceptible to glutamate excitotoxicity. In this study, we have investigated the expression of GLAST (EAAT1) and GLT-1 (EAAT2) in the retina of Brown Norway rats following induction of myelin oligodendrocyte glycoprotein (MOG)-EAE, which results in retinal ganglion cell (RGC) degeneration and dysfunction. In addition, we tested whether AAV-mediated overexpression of GLAST in the retina can protect RGCs from degeneration. To address the impact of glutamate transporter modulation on RGCs, we performed whole-cell recordings and measured tonic NMDA receptor-mediated currents in the absence and presence of a glutamate-uptake blocker. We report that αOFF-RGCs show larger tonic glutamate-induced currents than αON-RGCs, in line with their greater vulnerability under neuroinflammatory conditions. We further show that increased AAV-mediated expression of GLAST in the retina does indeed protect RGCs from degeneration during the inflammatory disease. Collectively, our study highlights the neuroprotective role of glutamate transporters in the EAE retina and provides a characterization of tonic glutamate-currents of αRGCs. The larger effects of increased extracellular glutamate concentration on the αOFF-subtype may underlie its enhanced vulnerability to degeneration.

Inhibiting microglia exacerbates the early effects of cuprizone in males in a rat model of multiple sclerosis, with no effect in females.

Hyper-activity of the brain's innate immune cells, microglia, is a hallmark of multiple sclerosis (MS). However, it is not clear whether this involvement of microglia is beneficial or detrimental or whether manipulating microglial activity may be therapeutic. We investigated if inhibiting microglial activity with minocycline prevents the early changes in oligodendrocyte and myelin-related markers associated with a demyelinating challenge in adult female and male rats. Cuprizone reduced the expression of myelin and oligodendrocyte genes in both females and males, reflective of cuprizone intoxication and the early phases demyelination, and reduced the number of oligodendrocytes in the corpus callosum. However, we see notable differences in the role for microglia in this response between females and males. In males, myelin and oligodendrocyte genes, as well as oligodendrocytes were also reduced by minocycline treatment; an effect that was not seen in females. In males, but not females, early changes in oligodendrocyte and myelin-related genes were associated with microglial proliferation in corpus callosum, and this increase was reversed by minocycline. These data indicate sex-specific effects of inhibiting microglia on the early changes leading to demyelination in an MS model and suggest microglia may play a key role in myelin stability in males but not in females. This highlights a strong need for sex-specific understanding of disease development in MS and suggest that treatments targeting microglia may be more effective in males than in females due to differing mechanisms of disease progression.

Exercise regulates NG2-expressing cells in a cuprizone-induced demyelination rat model of multiple sclerosis

Exercise regulates NG2-expressing cells in a cuprizone-induced demyelination rat model of multiple sclerosis

The preventive effect of Zingiber officinale essential oil on demyelination of corpus callosum in a cuprizone rat model of multiple sclerosis.

Multiple sclerosis (MS) is the most prevalent neurological disability among young adults. Anti-inflammatory drugs have shown to be effective in MS. The anti-inflammatory and antioxidative properties of Zingiber officinale (ginger) have been shown and proven in many phytotherapy studies. This study aimed to evaluate effects of ginger essential oil on preventing myelin degradation in a rat model of MS. In this study, we divided 49 rats into 7 groups; 4 control and 3 experimental groups that received 3 different dose of ginger essential oil (50, 100, and 150 mg/kg/day) for treatment of cuprizone-induced demyelinated rats. Basket test and transmission electron microscopy were performed in this study. Olig2 and Mbp genes and proteins were respectively evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Histologically, cuprizone created demyelination in the corpus callosum fibers. Remyelination of fibers was seen in the group treated with the medium dose of ginger essence, by toluidine blue staining. transmission electron microscopy (TEM) revealed increased thickness of the myelin of fibers in all 3 treated groups (p<0.05). Feeding by the medium dose of ginger essence significantly increased the levels of Mbp and Olig2 genes (p<0.05). ELISA test showed that 100 mg/kg/day of ginger caused a significant difference between experimental and the cuprizone-induced groups (p<0.05). Our findings suggested that administration of ginger essential oil prevented demyelination and improved remyelination of rats` corpus callusom and can be used as an effective substance in the prevention of MS.

Ultrasound Neuromodulation Reduces Demyelination in a Rat Model of Multiple Sclerosis.

Microglia, astrocytes, and oligodendrocyte progenitor cells (OPCs) may serve as targets for remyelination-enhancing therapy. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated to ameliorate myelin loss and inhibit neuroinflammation in animal models of brain disorders; however, the underlying mechanisms through which LIPUS stimulates remyelination and glial activation are not well-understood. This study explored the impacts of LIPUS on remyelination and resident cells following lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5 μL of 1% LPC into the rat hippocampus, and the treatment groups received daily LIPUS stimulation for 5 days. The therapeutic effects of LIPUS on LPC-induced demyelination were assessed through immunohistochemistry staining. The staining was performed to evaluate remyelination and Iba-1 staining as a microglia marker. Our data revealed that LIPUS significantly increased myelin basic protein (MBP) expression. Moreover, the IHC results showed that LIPUS significantly inhibited glial cell activation, enhanced mature oligodendrocyte density, and promoted brain-derived neurotrophic factor (BDNF) expression at the lesion site. In addition, a heterologous population of microglia with various morphologies can be found in the demyelination lesion after LIPUS treatment. These data show that LIPUS stimulation may serve as a potential treatment for accelerating remyelination through the attenuation of glial activation and the enhancement of mature oligodendrocyte density and BDNF production.

The effect of Zingiber Officinale Extract on Preventing Demyelination of Corpus Callosum in a Rat Model of Multiple Sclerosis

Background:Multiple sclerosis is the most prevalent neurological disability of young adults. Anti-inflammatory drugs have relative effects on MS. The anti-inflammatory and antioxidative effects of Zingiber officinale (ginger) have been proven in some experimental and clinical investigations. The aim of this study was to evaluate the effects of ginger extract on preventing myelin degradation in a rat model of MS. Methods: Forty nine male Wistar rats were used in this study and divided into four control groups: the normal group, cuprizone-induced group, sham group (CPZ + NaCMC), standard control group (fingolimod + cuprizone), including three experimental groups of CPZ, each receiving three different doses of ginger extract: 150, 300, and 600mg/kg /kg/day.Results:Ginger extract of 600 mg/kg prevented CC from demyelination; however, a significant difference was observed in the fingolimod group (p < 0.05). Difference in the CPZ group was quite significant (p < 0.05).Conclusion:Treatment with ginger inhibited demyelination and alleviated remyelination of corpus callosum in rats. Therefore, it could serve as a therapeutic agent in the MS.

Magnetization transfer ratio for assessing remyelination after transcranial ultrasound stimulation in the lysolecithin rat model of multiple sclerosis.

It has been shown that transcranial ultrasound stimulation (TUS) is capable of attenuating myelin loss and providing neuroprotection in animal models of brain disorders. In this study, we investigated the ability of TUS to promote remyelination in the lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5μL LPC (1%) into the rat hippocampus and the treated group received daily TUS for 5 or 12days. Magnetic resonance imaging techniques, including magnetization transfer ratio (MTR) and T2-weighted imaging, were used to longitudinally characterize the demyelination model. Furthermore, the therapeutic effects of TUS on LPC-induced demyelination were assessed by Luxol fast blue (LFB) staining. Our data revealed that reductions in MTR values observed during demyelination recover almost completely upon remyelination. The MTR values in demyelinated lesions were significantly higher in TUS-treated rats than in the LPC-only group after undergoing TUS. Form histological observation, TUS significantly reduced the size of demyelinated lesion 7days after LPC administration. This study demonstrated that MTR was a sensitive and reproducible quantitative marker to assess remyelination process in vivo during TUS treatment. These findings might open new promising treatment strategies for demyelinating diseases such as multiple sclerosis.

Vitamin B Complex and Experimental Autoimmune Encephalomyelitis -Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis.

The present study aimed to investigate the neuroprotective effects of the vitamin B complex (B1, B2, B3, B5, B6, and B12—VBC), by studying the changes in the femoral nerve, quadriceps muscle, popliteal lymph nodes and gut microbiota in the rat model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). VBC treatment attenuated clinical signs of EAE during the disease, and reduced the duration of EAE thereby contributing to a faster recovery. In VBC-treated EAE rats, a significant decrease in nerve and muscle nuclear density was revealed during the onset period of the disease, while a marked increase was detected at the end of the disease, compared with untreated EAE rats. In the lymph nodes of VBC-treated EAE rats, a fewer number of lymphoid follicles in the cortical area and smaller epithelioid granulomas were detected. The changes in microbiota composition were examined using 16S rRNA gene sequencing and bioinformatics analysis, which revealed the potential of VBC treatment in establishing and/or maintaining gut microbiota homeostasis. Finally, the present study demonstrated that VBC treatment ameliorated the cellular changes in the affected peripheral nerve, muscles innervated by this nerve, and the gut microbiota dysbiosis which occurred during the EAE.

Dimethyl fumarate decreases short-term but not long-term inflammation in a focal EAE model of neuroinflammation

BackgroundDimethyl fumarate (DMF) is an oral immunomodulatory drug used in the treatment of autoimmune diseases. Here, we sought to study whether the effect of DMF can be detected using positron emission tomography (PET) targeting the 18-kDa translocator protein (TSPO) in the focal delayed-type hypersensitivity rat model of multiple sclerosis (fDTH-EAE). The rats were treated orally twice daily from lesion activation (day 0) with either vehicle (tap water with 0.08% Methocel, 200 µL; control group n = 4 (3 after week four)) or 15 mg/kg DMF (n = 4) in 0.08% aqueous Methocel (200 µL) for 8 weeks. The animals were imaged by PET using the TSPO tracer [18F]GE-180 in weeks 0, 1, 2, 4, 8, and 18 following lesion activation, and the non-displaceable binding potential (BPND) was calculated. Immunohistochemical staining for Iba1, CD4, and CD8 was performed in week 18, and in separate cohorts of animals, following 2 or 4 weeks of treatment.ResultsUsing the fDTH-EAE model, DMF reduced the [18F]GE-180 BPND in the DMF-treated animals compared to control animals after 1 week of treatment (two-tailed unpaired t test, p = 0.031), but not in weeks 2, 4, 8, or 18 when imaged in vivo by PET. Immunostaining for Iba1 showed that DMF had no effect on the perilesional volume or the core lesion volume after 2 or 4 weeks of treatment, or at 18 weeks. However, the optical density (OD) measurements of CD4+ staining showed reduced OD in the lesions of the treated rats.ConclusionsDMF reduced the microglial activation in the fDTH-EAE model after 1 week of treatment, as detected by PET imaging of the TSPO ligand [18F]GE-180. However, over an extended time course, reduced microglial activation was not observed using [18F]GE-180 or by immunohistochemistry for Iba1+ microglia/macrophages. Additionally, DMF did affect the infiltration of CD4+ and CD8+ T-lymphocytes at the fDTH-EAE lesion.

Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a neuroinflammatory disease with expanding axonal and neuronal degeneration and demyelination in the central nervous system, leading to motor dysfunctions, psychical disability, and cognitive impairment during MS progression. Positron emission tomography (PET) is an imaging technique able to quantify in vivo cellular and molecular alterations. Radiotracers with affinity to intact myelin can be used for in vivo imaging of myelin content changes over time. It is possible to detect either an increase or decrease in myelin content, what means this imaging technique can detect demyelination and remyelination processes of the central nervous system. In this protocol we demonstrate how to use PET imaging to detect myelin changes in the lysolecithin rat model, which is a model of focal demyelination lesion (induced by stereotactic injection) (i.e., a model of multiple sclerosis disease). 11C-PIB PET imaging was performed at baseline, and 1 week and 4 weeks after stereotaxic injection of lysolecithin 1% in the right striatum (4 µL) and corpus callosum (3 µL) of the rat brain, allowing quantification of focal demyelination (injection site after 1 week) and the remyelination process (injection site at 4 weeks). Myelin PET imaging is an interesting tool for monitoring in vivo changes in myelin content which could be useful for monitoring demyelinating disease progression and therapeutic response.

Vitamin B12 and estradiol benzoate improve memory retrieval through activation of the hippocampal AKT, BDNF, and CREB proteins in a rat model of multiple sclerosis.

Objective(s):Multiple sclerosis (MS) causes extensive damage in the hippocampus. Vitamin B12 (vit B12) and estradiol benzoate (EB) have anti-inflammatory and re-myelination properties that make them proper in improvement of cognitive impairment. This study aimed to evaluate the effects of these compounds on learning and memory disturbances. Materials and Methods:77 adult male rats were implanted with stainless steel guide cannula bilaterally into the hippocampal area. The animals received 3 μl intrahippocampal EtB 0.01% and were randomly divided into eleven groups (7 rats/group). The groups included control, peanut oil (sham1), distilled water (sham 2), vit B12 (0.25, 0.5, 1 mg/kg), EB (25 and 50 mg/kg), vit B12 (0.25 mg/kg) plus EB (25 mg/kg), vit B12 (0.5 mg/kg) plus EB (25 mg/kg), and vit B12 (1 mg/kg) plus EB (50 mg/kg). The control group received intrahippocampal saline (as solvent). The locomotor activity and learning and memory functions were evaluated by open-field and shuttle-box tests, respectively. AKT, CREB, and BDNF levels were analyzed by Western blotting.Results:This study has found significant deficit in passive avoidance learning, locomotor activity, as well as decrease in the levels of phosphorylated AKT, BDNF, and CREB in groups that received EtB. Vit B12 (1 mg/kg), EB (50 mg/kg), and their combination markedly improved these side effects.Conclusion:This study demonstrated that vit B12 and estradiol benzoate, especially in combination therapy, can be helpful in treatment of memory problems and MS-induced dysfunction through activation of the hippocampal AKT, BDNF, and CREB proteins.

Glial cell activation and altered metabolic profile in the spinal-trigeminal axis in a rat model of multiple sclerosis associated with the development of trigeminal sensitization

Trigeminal neuralgia is often an early symptom of multiple sclerosis (MS), and it generally does not correlate with the severity of the disease. Thus, whether it is triggered simply by demyelination in specific central nervous system areas is currently questioned. Our aims were to monitor the development of spontaneous trigeminal pain in an animal model of MS, and to analyze: i) glial cells, namely astrocytes and microglia in the central nervous system and satellite glial cells in the trigeminal ganglion, and ii) metabolic changes in the trigeminal system. The subcutaneous injection of recombinant MOG1-125 protein fragment to Dark Agouti male rats led to the development of relapsing-remitting EAE, with a first peak after 13 days, a remission stage from day 16 and a second peak from day 21. Interestingly, orofacial allodynia developed from day 1 post injection, i.e. well before the onset of EAE, and worsened over time, irrespective of the disease phase. Activation of glial cells both in the trigeminal ganglia and in the brainstem, with no signs of demyelination in the latter tissue, was observed along with metabolic alterations in the trigeminal ganglion. Our data show, for the first time, the spontaneous development of trigeminal sensitization before the onset of relapsing-remitting EAE in rats. Additionally, pain is maintained elevated during all stages of the disease, suggesting the existence of parallel mechanisms controlling motor symptoms and orofacial pain, likely involving glial cell activation and metabolic alterations which can contribute to trigger the sensitization of sensory neurons.

In vivo Characterization of Four 18F-Labeled S1PR1 Tracers for Neuroinflammation.

The sphingosine-1-phosphate receptor 1 (S1PR1) is an important biomarker for imaging inflammation in the central nervous system (CNS). Herein, we report our recent evaluation of four 18F-labeled S1PR1 tracers (18F-TZ43113, 18F-TZ35104, 18F-TZ4877, and 18F-TZ4881) in a rat model of multiple sclerosis (MS). MicroPET studies of each tracer's uptake and kinetics were performed in an experimental autoimmune encephalomyelitis (EAE) rat model of MS to quantify upregulated S1PR1 expression in the lumbar spinal cord of EAE rats. Western blot analysis was conducted to confirm the differences in the expression of S1PR1 protein level between EAE and sham rats. Radiometabolite analysis was performed for the most promising candidate in rats. All four S1PR1 tracers detected increased S1PR1 levels in response to neuroinflammation in the lumbar spinal cord of EAE rats, which was supported by western blot results. The ranked order of tracer uptake in rat spinal cord was 18F-TZ4877 > 18F-TZ4881 > 18F-TZ35104 > 18F-TZ43113. 18F-TZ4877 had the highest uptake of the four tracers and showed good kinetic modeling fits in rat spinal cord using an image-based method of arterial blood input function. Radiometabolite analysis of 18F-TZ4877 showed good in vivo stability with no major radiometabolite accumulation in the ratbrain. Among these four new PET tracers, 18F-TZ4877 showed the most favorable profile for assessing S1PR1 expression in the EAE rat model of MS. Further characterization of these radiotracers in other models of neuroinflammation is warranted to identify a promising 18F-labeled tracer for imaging S1PR1 in vivo.

The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis

Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.

Astaxanthin Reduces Demyelination and Oligodendrocytes Death in A Rat Model of Multiple Sclerosis.

Objective Astaxanthin (AST) is a carotenoid with anti-oxidative, anti-inflammatory, and anti-apoptotic properties. It has also been reported that AST exerts protective effects against neurodegenerative diseases and reduces oxidative stress-induced the central nervous system (CNS) injury. In this study, we aimed to evaluate the protective potential of AST in inhibiting demyelination and oligodendrocyte death in a rat model of multiple sclerosis (MS). Materials and Methods In this experimental study, forty Wistar rats were randomly assigned to four experimental groups: control group (with normal feeding), cuprizone (CPZ group) that daily received 0.6% CPZ for 4 weeks, sham group that daily received 0.6% CPZ plus dimethyl sulfoxid (DMSO) for 4 weeks, and AST group that daily received 0.6% CPZ and after 12 hours were treated with AST (3 mg/kg), for 4 weeks. Muscle strength was evaluated by the behavioral basket test at the end of every week for 4 weeks. Luxol Fast Blue (LFB) staining was utilized for the identification of myelination and demyelination. Myelin density was evaluated by the ImageJ software. The expression of A2B5 (oligodendrocyte precursor protein) and myelin oligodendrocyte protein (MOG) were assessed by immunohistochemistry (IHC) and the expression of myelin basic protein (MBP), MOG, and platelet-derived growth factor-alpha (PDGFR-α) genes was examined by the real-time polymerase chain reaction (RT-PCR) technique. Results The administration of AST reduced the oligodendrocyte damage and myelin sheath disruption in a rat model of MS. The basket behavioral test showed the improvement of muscle strength in the AST group compared with CPZ and sham groups. Besides, the results of real-time PCR and IHC indicated the beneficial effects of AST in declining demyelination and oligodendrocyte death in a rat model of MS. ConclusionAST reduces damages to the myelin sheath and oligodendrocyte death in a rat model of MS.

Improvement of Remyelination in Demyelinated Corpus Callosum Using Human Adipose-Derived Stem Cells (hADSCs) and Pregnenolone in the Cuprizone Rat Model of Multiple Sclerosis.

Adipose-derived stem cells (ASCs) have neuroprotective effects, and their repair ability has been approved in neurodegenerative studies. Pregnenolone as a neurosteroid plays significant roles in neurogenesis. We aimed to consider the effect of ADSCs and pregnenolone injection on the multiple sclerosis (MS) model created by cuprizone. Male Wistar rats (n = 36) were fed with an ordinary diet or a diet with cuprizone (0.6%) for 3weeks. H-ADSCs were taken from patients with lipoaspirate surgery. The rats were divided into six groups (n=6): healthy, MS, sham, pregnenolone injection, ADSCs injection, pregnenolone and ADSCs injection. Behavioral test, histological examination and TEM were conducted. The specific markers for myelin and cell differentiation were assessed using immunohistochemistry staining. Additionally, the measure of MBP and MOG gene expression and the amount of related proteins were determined using real-time RT-PCR and ELISA techniques, respectively. Histologic results showed that induced demyelination in corpus callosum fibers. TEM revealed an increased thickness of myelin in fibers in the treated groups (P < 0.05). Injection of hADSC and pregnenolone significantly increased the expression levels of MBP and MOG (P < 0.001). The mean percentage of MOG and MBP markers were significantly increased in the treated groups compared to MS and sham groups (P < 0.05). Moreover, the OD level of MBP and MOG proteins showed that their values in the ADSCs/pregnenolone group were close to those of the control group without a significant difference. Our data indicated the remyelination potency and cell differentiation can improve with ADSCs and pregnenolone treatments in the multiple sclerosis model which created by cuprizone in rats.

In-vivo Assessment of Neurotoxicological Effect of Mugwort Leaves on Induced Rat Model of Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating ailment in which the loss of myelin destructs conduction along the affected axons typically resulting in the conduction block. The motive of this protocol is to carry out the neuroprotective activity of Artemisia vulgaris (Mugwort) by induced demyelination of ethidium Bromide in wistar rats. The leaf methanolic extract was treated at 100mg/kg and 200mg/kg weight administered through oral route and continued for 28 days in demyelinated rats. Demyelination was affected by administering intracranial injection of toxin (ethidium Bromide) at the dose of 1µg/0.03ml of PBS per kg body weight. The potency of the extract was analysed in the terms of their behavioural study on the first, second and fourth week. The animals were immolate after 28 days and subjected to histopathological assessment. The unearthing from behavioural histopathological and biochemical studies evince that the methanol extract of Artemisia vulgaris have potential protective effect on the ethidium bromide induced demyelinated rats.

β-synuclein at the "synapse" of encephalitis and neurodegeneration in multiple sclerosis?

Lodygin and colleagues recently identified a candidate grey matter target antigen in a rat model of multiple sclerosis, a disease classically associated with the white matter antigen, myelin.