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  1. Thematic analysis of multiple sclerosis research by enhanced strategic diagram
    Shafin N, Ismail CAN, Mustafa MZ, Ghani N, Ahmad AH, Othman Z, et al.
    Mult Scler, 2022 Dec;28(14):2160-2170.
    PMID: 35164590 DOI: 10.1177/13524585221075542
    Recent interest in multiple sclerosis research warrants literature analysis to evaluate the current state of the discipline and new research domains. This bibliometric review summarised the research trends and analysed research areas in multiple sclerosis over the last decade. The documents containing the term 'multiple sclerosis' in the article title were retrieved from the Scopus database. We used Harzing's Publish or Perish and VOSviewer for citation analysis and data visualisation, respectively. We found a total of 18,003 articles published in journals in the English language between 2012 and 2021. The emerging keywords identified utilising the enhanced strategic diagram were 'covid-19', 'teriflunomide', 'clinical trial', 'microglia', 'b cells', 'myelin', 'brain', 'white matter', 'functional connectivity', 'pain', 'employment', 'health-related quality of life', 'meta-analysis' and 'comorbidity'. This study demonstrates the tremendous growth of multiple sclerosis literature worldwide, which is expected to grow more than double during the next decade especially in the identified emerging topics.
    Matched MeSH terms: Myelin Sheath
  2. Fulltext Evaluation of neuroprotective effects of alpha-tocopherol in cuprizone-induced demyelination model of multiple sclerosis
    Mitra NK, Xuan KY, Teo CC, Xian-Zhuang N, Singh A, Chellian J
    Res Pharm Sci, 2020 Dec;15(6):602-611.
    PMID: 33828603 DOI: 10.4103/1735-5362.301345
    Background and Purpose: Multiple sclerosis (MS) is an autoimmune disorder characterized by demyelination and axonal loss. Quantitative estimation of behavioral, locomotor, and histological changes following the use of alpha-tocopherol (AT) in the animal model of MS have not been reported. The present study was planned to evaluate whether AT can improve sensorimotor dysfunction and reduce demyelination in the cuprizone (CPZ)-induced rat model of MS.

    Experimental approach: Female Sprague-Dawley rats (8 weeks) were fed with cuprizone diet for 5 weeks followed by intraperitoneal injections of alpha-tocopherol (100 mg/Kg) or PBS for 2 weeks (groups E1 and E2, n = 8). Group C (n = 8) was fed with normal pellets followed by intraperitoneal doses of PBS. Open-field test and beam walking were carried out on every 10th day. The mean area of demyelination in the corpus callosum was quantified in Luxol® fast blue (LFB) stained histological sections of the forebrain. Qualitative grading for relative changes in the stains of myelinated fibers was also done.

    Findings/Results: During withdrawal of CPZ, AT treatment increased the average speed by 22% in group E1, compared to group E2 (P < 0.05). The mean time to walk the beam was reduced in group E1 by 2.6% compared to group E2 (P < 0.05). The rearing frequency was increased in group E1 during week 6-7 compared to that in the period of CPZ treatment. The mean area of demyelination in the corpus callosum showed a 12% reduction in group E1 compared to group E2 (P < 0.05).

    Conclusion and implications: Short-term AT therapy showed improvement in motor dysfunction and reduction of demyelination in the animal model of MS.

    Matched MeSH terms: Myelin Sheath
  3. Fulltext Major cellular events in peripheral nerve regeneration: A brief overview
    Naidu, M., David, P.
    International Medical Journal Malaysia, 2009;8(1):61-64.
    MyJurnal
    Injury to a peripheral nerve leads to degeneration of the segment distal to the site of lesion, a process referred to as Wallerian degeneration. During Wallerian degeneration, axons and myelin sheaths undergo degeneration and are phagocytosed by macrophages and Schwann cells. The Schwann cells proliferate and the endoneurial tubes persist, together the whole structure is known as the band of Büngner. Within few hours, the damaged axons in the proximal stump initiate a regeneration response, with formation of new growth cones. During Wallerian degeneration, neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors are upregulated to facilitate regeneration. The recovery of the target in mammals is often variable, but almost never complete. In humans, scar tissue forms at the site of lesion and this often results in poor recovery of the target. The major events underlying this regenerative process is highlighted and discussed in this review.
    Matched MeSH terms: Myelin Sheath
  4. Fulltext The role of cells, neurotrophins, extracellular matrix and cell surface molecules in peripheral nerve regeneration
    Naidu M
    Malays J Med Sci, 2009 Apr;16(2):10-4.
    PMID: 22589652 MyJurnal
    Wallerian degeneration is a complicated process whereby axons and myelin sheaths undergo degeneration, and eventually are phagocytosed by macrophages and Schwann cells following nerve damage. Schwann cells proliferate and the endoneural tubes persist. In addition, neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors are upregulated to facilitate regeneration. The important role of cellular components, neurotrophins, and extracellular matrix components, including cell surface molecules involved in this regenerative process, is highlighted and discussed in this review.
    Matched MeSH terms: Myelin Sheath
  5. Fulltext Pontine myelinolysis following correction of hyponatraemia
    Loo CS, Lim TO, Fan KS, Murad Z, Suleiman AB
    Med J Malaysia, 1995 Jun;50(2):180-2.
    PMID: 7565192
    A patient with severe hyponatreamia secondary to chronic renal failure was treated with peritoneal dialysis (PD). On the third day of admission, she developed progressive obtundation. Neurological examination showed bilateral brisk reflexes with intact brain stem reflexes. Magnetic resonance imaging demonstrated patchy demyelination of the pontine area indicating central pontine myelinolysis (CPM). Despite supportive measures, the patient died on the fifteenth day of admission. The rate of correction of hyponatraemia with peritoneal dialysis can be rapid and detrimental to hyponatraemic chronic renal failure patients and careful monitoring of serum sodium level is advocated.
    Matched MeSH terms: Myelin Sheath/physiology*
  6. Prenatal alcohol exposure and early postnatal changes in the developing nerve-muscle system
    David P, Subramaniam K
    Birth Defects Res. Part A Clin. Mol. Teratol., 2005 Nov;73(11):897-903.
    PMID: 16228975
    Extensive research on prenatal alcohol exposure has proven the potent teratogenicity of this substance of abuse. Children born to alcoholic mothers are often diagnosed with fetal alcohol syndrome (FAS). Those afflicted with FAS often have muscle weakness, muscle wasting, and atrophy. This study assessed the effects of prenatal alcohol exposure on the developing rat neuromuscular system.
    Matched MeSH terms: Myelin Sheath/enzymology; Myelin Sheath/pathology
  7. Efficacy of Human Cell-Seeded Muscle-Stuffed Vein Conduit in Rat Sciatic Nerve Repair
    Ramli K, Gasim AI, Ahmad AA, Htwe O, Mohamed Haflah NH, Law ZK, et al.
    Tissue Eng Part A, 2019 10;25(19-20):1438-1455.
    PMID: 30848172 DOI: 10.1089/ten.TEA.2018.0279
    We investigated the efficacy of a muscle-stuffed vein (MSV) seeded with neural-transdifferentiated human mesenchymal stem cells as an alternative nerve conduit to repair a 15-mm sciatic nerve defect in athymic rats. Other rats received MSV conduit alone, commercial polyglycolic acid conduit (Neurotube®), reverse autograft, or were left untreated. Motor and sensory functions as well as nerve conductivity were evaluated for 12 weeks, after which the grafts were harvested for histological analyses. All rats in the treatment groups demonstrated a progressive increase in the mean Sciatic Functional Index (motor function) and nerve conduction amplitude (electrophysiological function) and showed positive withdrawal reflex (sensory function) by the 10th week of postimplantation. Autotomy, which is associated with neuropathic pain, was severe in rats treated with conduit without cells; there was mild or no autotomy in the rats of other groups. Histologically, harvested grafts from all except the untreated groups exhibited axonal regeneration with the presence of mature myelinated axons. In conclusion, treatment with MSV conduit is comparable to that of other treatment groups in supporting functional recovery following sciatic nerve injury; and the addition of cells in the conduit alleviates neuropathic pain. Impact Statement It is shown that pretreated muscle-stuffed vein conduit is comparable to that of commercial nerve conduit and autograft in supporting functional recovery following peripheral nerve injury. The addition of neural-differentiated mesenchymal stem cells in the conduit is shown to alleviate neuropathic pain.
    Matched MeSH terms: Myelin Sheath/ultrastructure
  8. Fulltext From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
    Paudel YN, Angelopoulou E, Piperi C, Gnatkovsky V, Othman I, Shaikh MF
    Curr Neuropharmacol, 2020;18(11):1126-1137.
    PMID: 32310049 DOI: 10.2174/1570159X18666200420125017
    Epilepsy is a devastating neurological condition characterized by long-term tendency to generate unprovoked seizures, affecting around 1-2 % of the population worldwide. Epilepsy is a serious health concern which often associates with other neurobehavioral comorbidities that further worsen disease conditions. Despite tremendous research, the mainstream anti-epileptic drugs (AEDs) exert only symptomatic relief leading to 30% of untreatable patients. This reflects the complexity of the disease pathogenesis and urges the precise understanding of underlying mechanisms in order to explore novel therapeutic strategies that might alter the disease progression as well as minimize the epilepsy-associated comorbidities. Unfortunately, the development of novel AEDs might be a difficult process engaging huge funds, tremendous scientific efforts and stringent regulatory compliance with a possible chance of end-stage drug failure. Hence, an alternate strategy is drug repurposing, where anti-epileptic effects are elicited from drugs that are already used to treat non-epileptic disorders. Herein, we provide evidence of the anti-epileptic effects of Fingolimod (FTY720), a modulator of sphingosine-1-phosphate (S1P) receptor, USFDA approved already for Relapsing-Remitting Multiple Sclerosis (RRMS). Emerging experimental findings suggest that Fingolimod treatment exerts disease-modifying anti-epileptic effects based on its anti-neuroinflammatory properties, potent neuroprotection, anti-gliotic effects, myelin protection, reduction of mTOR signaling pathway and activation of microglia and astrocytes. We further discuss the underlying molecular crosstalk associated with the anti-epileptic effects of Fingolimod and provide evidence for repurposing Fingolimod to overcome the limitations of current AEDs.
    Matched MeSH terms: Myelin Sheath
  9. Fulltext Effectiveness of flaxseed oil on peripheral nerve regeneration following crush injury of sciatic nerve in rat: behavioural analysis and an electron microscopic study
    Muhammad Danial Che Ramli, Nur Amira Sumari, Neni Widiasmoro Selamat, Hussin Muhammad, Junedah Sanusi
    Malaysian Journal of Medicine and Health Sciences, 2020;16(101):106-111.
    MyJurnal
    Introduction: Peripheral nerve injuries (PNI) are a disabling injury as it often results in motor and sensory deficit with cognitive impairment. Flaxseed oil provides a good source of omega-3 fatty acid and it is believed to be able to protect the damaged nerve cell for successful nerve recovery. This study aimed to investigate a potential neuro-re- generation properties of flaxseed oil in treating the PNI. Methods: A total of 65 rats were separated into 4 groups: Group 1: Normal group (n=5), Group 2: Negative group (n=20), Group 3: Experimental group (n=20) and Group 4: Positive control (n=20), all the group were further divided into 4 groups (post-operative 7, 14, 21, 28 days, n=5 for each days). The functional restoration was assessed by walking track analysis (Sciatic Functional Index analysis-SFI) and toe spreading reflex (grading score). Electron microscope studies were performed on sciatic nerve to evaluate the regenerative process through morphologic and morphometric changes. Results: Oral administration of flaxseed oil (experimental group) at 1000 mg/kg body weight/day showed better recovery compared to negative control value. However, there was no significant difference in SFI and toe spreading reflex between positive (mecobalamin) and experimental group (flaxseed oil). Morphological and morphometrical findings indicated increases in the myelin thickness and myelin sheath layer after administration of flaxseed oil. Conclusion: The flaxseed oil supplementation could enhance the neurorestorative capacities of injured sciatic nerve.
    Matched MeSH terms: Myelin Sheath
  10. Fulltext Effect of tocotrienol rich fraction (TRF) on muscles reinnervation after sciatic nerve crush injury in rats
    Amalia Lailanor, Nurul Alaina Hj Yahya, Junedah Sanusi, Huzwah Khaza’ai, Muhammad Danial Che Ramli
    Malaysian Journal of Medicine and Health Sciences, 2020;16(101):118-124.
    MyJurnal
    Introduction: Muscle denervation is a process where muscles lose nerve supply due to neural damage and this may lead to paralysis in human. Muscle denervation is mainly caused by peripheral nerve injuries especially in the lower extremities that resulted in devastating effect on human daily functions and routines. Tocotrienol Rich Fraction (TRF) consist of 75% of tocotrienols have shown potential neuroprotective properties. The objective of this study is to ob- serve motor coordination and histological characteristics on muscles that underwent sciatic nerve crush injury and supplemented with TRF. Methods: A total of 104 Sprague-Dawley rats were divided into four groups; normal group (n=8) with no sciatic nerve crush injury, negative control (n=32) with sciatic nerve crush injury at hindlimb without treatment, positive control (n=32) sciatic nerve crush injury treated with 500 µg/kg/day of methylcobalamin, and experimental group (n=32) of rats that underwent sciatic nerve crush injury and treated with 200 mg/kg/day of TRF. Result: Skeletal muscles which located at hind limb; Soleus Muscle and Extenstor Digitorum Longus Muscle (EDL) muscle have shown an increasing in weight when it is supplemented with TRF 200 mg/kg/day and improved myelin layer of nerve. Conclusion: This study showed that TRF has the potency to improve reinnervation rate and neuron supply in hind muscle.
    Matched MeSH terms: Myelin Sheath
  11. Fulltext Centella asiatica (L.)-Neurodifferentiated Mesenchymal Stem Cells Promote the Regeneration of Peripheral Nerve
    Hussin HM, Lawi MM, Haflah NHM, Kassim AYM, Idrus RBH, Lokanathan Y
    Tissue Eng Regen Med, 2020 04;17(2):237-251.
    PMID: 32036567 DOI: 10.1007/s13770-019-00235-6
    BACKGROUND: Centella asiatica (L.) is a plant with neuroprotective and neuroregenerative properties; however, its effects on the neurodifferentiation of mesenchymal stem cells (MSCs) and on peripheral nerve injury are poorly explored. This study aimed to investigate the effects of C. asiatica (L.)-neurodifferentiated MSCs on the regeneration of peripheral nerve in a critical-size defect animal model.

    METHODS: Nerve conduit was developed using decellularised artery seeded with C. asiatica-neurodifferentiated MSCs (ndMSCs). A 1.5 cm sciatic nerve injury in Sprague-Dawley rat was bridged with reversed autograft (RA) (n = 3, the gold standard treatment), MSC-seeded conduit (MC) (n = 4) or ndMSC-seeded conduit (NC) (n = 4). Pinch test and nerve conduction study were performed every 2 weeks for a total of 12 weeks. At the 12th week, the conduits were examined by histology and transmission electron microscopy.

    RESULTS: NC implantation improved the rats' sensory sensitivity in a similar manner to RA. At the 12th week, nerve conduction velocity was the highest in NC compared with that of RA and MC. Axonal regeneration was enhanced in NC and RA as shown by the expression of myelin basic protein (MBP). The average number of myelinated axons was significantly higher in NC than in MC but significantly lower than in RA. The myelin sheath thickness was higher in NC than in MC but lower than in RA.

    CONCLUSION: NC showed promising effects on nerve regeneration and functional restoration similar to those of RA. These findings revealed the neuroregenerative properties of C. asiatica and its potential as an alternative strategy for the treatment of critical size nerve defect.

    Matched MeSH terms: Myelin Sheath
  12. Fulltext Changes in white matter fiber density and morphology across the adult lifespan: A cross-sectional fixel-based analysis
    Choy SW, Bagarinao E, Watanabe H, Ho ETW, Maesawa S, Mori D, et al.
    Hum Brain Mapp, 2020 08 15;41(12):3198-3211.
    PMID: 32304267 DOI: 10.1002/hbm.25008
    White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel-based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion-weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age-related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age-related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello-thalamo-cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract-level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process.
    Matched MeSH terms: Myelin Sheath
  13. Fulltext The Changes in Rats with Sciatic Nerve Crush Injury Supplemented with Evening Primrose Oil: Behavioural, Morphologic, and Morphometric Analysis
    Ramli D, Aziz I, Mohamad M, Abdulahi D, Sanusi J
    Evid Based Complement Alternat Med, 2017;2017:3476407.
    PMID: 28620418 DOI: 10.1155/2017/3476407
    Nerve crush injuries are commonly used models for axonotmesis to examine peripheral nerve regeneration. As evening primrose oil (EPO) is rich in omega-6 essential fatty acid component and gamma-linolenic acid, studies have shown the potential role of EPO in myelination. Seventy-two healthy adult Sprague-Dawley rats were classified into three groups: normal group, control group, and experimental group. The result indicates that there was significant difference in toe-spreading reflex between the normal and the control groups (1.9 ± 0.031, p < 0.05) and the normal and the EPO groups (0.4 ± 0.031, p < 0.05) and significant difference between EPO and the control groups (1.5 ± 0.031, p < 0.05). Regeneration of axons and myelin in nerve fibre in the EPO-treated group developed better and faster than in the control group. In the control group, the shape of the axon was irregular with a thinner myelin sheath. In the experimental group, the shape of the axons, the thickness of the myelin sheath, and the diameter of the axons were almost the same as in the normal group. In conclusion, EPO supplementation may be beneficial as a therapeutic option for disturbances of nerve interaction.
    Matched MeSH terms: Myelin Sheath
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