Skip to content
2000
Volume 24, Issue 4
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Background

Multiple sclerosis (MS) is a persistent autoimmune condition characterized by inflammation and neurodegeneration. The current efficacy of treatments is limited, which has generated interest in developing neuroprotective strategies. Solid lipid nanoparticles (SLNs) and probiotics are potential drug delivery vehicles for targeting the CNS (Central nervous system), regulating immune responses, and supporting neuroprotection in neurological conditions.

Methods

The study investigates how SLNs containing RSG (rosiglitazone) and probiotics can protect the nervous system in cases of MS. We administered toxin EtBr (Ethidium bromide) from day 1 to day 7, later followed by the treatment from day 8 to day 35. During this time interval, various behavioural parameters have been performed. Further, after 35th day, blood plasma of animals was collected to study complete CBC profiling and animals were sacrificed. Then, biochemical and molecular studies, gross morphology of brain sectioning, histopathological evaluation and estimation of fatty acid content in fecal matter were performed.

Results

RSG shows neuroprotective effects by blocking the STAT-3 and mTOR signaling pathways and increasing the production of PPAR-gamma. GW9662, a PPAR-gamma antagonist given at a dose of 2 mg/kg (), was utilized to evaluate the role of PPAR-gamma and to compare the efficacy of RSG and probiotic-loaded SLNs in potentially providing neuroprotection. The relationship between RSG and the STAT-3, mTOR, and PPAR-gamma pathways in MS was confirmed and validated using analysis. RSG and probiotic-loaded SLNs modulate the complete blood profiling of rats and improve the symptoms of MS. We assessed the diagnostic capabilities of different biological samples such as cerebrospinal fluid, blood plasma, and brain homogenates (specifically from the hippocampus, striatum, cortex, and midbrain) to analyze neurochemical changes linked to neurobehavioral changes in the progression of MS.

Conclusion

The study showed that combining RSG and probiotics in an experimental medication form improved symptoms of MS more effectively than using RSG alone. This improvement is likely due to changes in STAT-3, mTOR, and PPAR-gamma signaling pathways.

Loading

Article metrics loading...

/content/journals/cnsnddt/10.2174/0118715273336107241015100912
2024-11-01
2025-04-24
Loading full text...

Full text loading...

References

  1. Vidal-JordanaA. MontalbanX. Multiple sclerosis.Neuroimaging Clin. N. Am.201727219520410.1016/j.nic.2016.12.001 28391781
    [Google Scholar]
  2. WangK. SongF. Fernandez-EscobarA. LuoG. WangJ.H. SunY. The properties of cytokines in multiple sclerosis: Pros and cons.Am. J. Med. Sci.2018356655256010.1016/j.amjms.2018.08.018 30447707
    [Google Scholar]
  3. FernándezÓ. Costa-FrossardL. Martínez-GinésM. MonteroP. PrietoJ.M. RamióL. The broad concept of “spasticity-plus syndrome” in multiple sclerosis: A possible new concept in the management of multiple sclerosis symptoms.Front. Neurol.20201115210.3389/fneur.2020.00152 32256440
    [Google Scholar]
  4. PithadiaA. JainS. NavaleA. Pathogenesis and treatment of multiple sclerosis (MS).Int. J. Neurol.2009102120
    [Google Scholar]
  5. GoodinD.S. KhankhanianP. GourraudP.A. VinceN. The nature of genetic and environmental susceptibility to multiple sclerosis.PLoS One2021163e024615710.1371/journal.pone.0246157 33750973
    [Google Scholar]
  6. NaegeleM. MartinR. The good and the bad of neuroinflammation in multiple sclerosis.Handb. Clin. Neurol.2014122598710.1016/B978‑0‑444‑52001‑2.00003‑0 24507513
    [Google Scholar]
  7. XinP. XuX. DengC. The role of JAK/STAT signaling pathway and its inhibitors in diseases.Int. Immunopharmacol.20208010621010.1016/j.intimp.2020.106210 31972425
    [Google Scholar]
  8. PhilipsR.L. WangY. CheonH. The JAK-STAT pathway at 30: Much learned, much more to do.Cell2022185213857387610.1016/j.cell.2022.09.023 36240739
    [Google Scholar]
  9. YangX. YvQ. YeF. Echinacoside protects dopaminergic neurons through regulating IL-6/JAK2/STAT3 pathway in Parkinson’s disease model.Front. Pharmacol.20221384881310.3389/fphar.2022.848813 35281889
    [Google Scholar]
  10. LashgariN.A. RoudsariN.M. MomtazS. SathyapalanT. AbdolghaffariA.H. SahebkarA. The involvement of JAK/STAT signaling pathway in the treatment of Parkinson’s disease.J. Neuroimmunol.202136157775810.1016/j.jneuroim.2021.577758 34739911
    [Google Scholar]
  11. ChibaT. YamadaM. AisoS. Targeting the JAK2/STAT3 axis in Alzheimer’s disease.Expert Opin. Ther. Targets200913101155116710.1517/14728220903213426 19663649
    [Google Scholar]
  12. RusekM. SmithJ. El-KhatibK. AikinsK. CzuczwarS.J. PlutaR. The role of the JAK/STAT signaling pathway in the pathogenesis of Alzheimer’s disease: New potential treatment target.Int. J. Mol. Sci.202324186410.3390/ijms24010864 36614305
    [Google Scholar]
  13. TrägerU MagnussonA Lahiri SwalesN JAK/STAT signalling in Huntington’s disease immune cells. PLoS Curr 2013; 5: ecurrents.hd.5791c897b5c3bebeed93b1d1da0c0648.10.1371/currents.hd.5791c897b5c3bebeed93b1d1da0c0648 24459609
    [Google Scholar]
  14. KooshkiL. ZarneshanS.N. FakhriS. MoradiS.Z. EcheverriaJ. The pivotal role of JAK/STAT and IRS/PI3K signaling pathways in neurodegenerative diseases: Mechanistic approaches to polyphenols and alkaloids.Phytomedicine202311215468610.1016/j.phymed.2023.154686 36804755
    [Google Scholar]
  15. KumarN. SharmaN. MehanS. Connection between JAK/STAT and PPARγ signaling during the progression of multiple sclerosis: Insights into the modulation of T-cells and immune responses in the brain.Curr. Mol. Pharmacol.202114582383710.2174/1874467214666210301121432 33645493
    [Google Scholar]
  16. BenvenisteE.N. LiuY. McFarlandB.C. QinH. Involvement of the janus kinase/signal transducer and activator of transcription signaling pathway in multiple sclerosis and the animal model of experimental autoimmune encephalomyelitis.J. Interferon Cytokine Res.201434857758810.1089/jir.2014.0012 25084174
    [Google Scholar]
  17. SchmitzT. ChewL.J. Cytokines and myelination in the central nervous system.ScientificWorldJournal200881119114710.1100/tsw.2008.140 18979053
    [Google Scholar]
  18. LiuY. HoldbrooksA.T. De SarnoP. Therapeutic efficacy of suppressing the Jak/STAT pathway in multiple models of experimental autoimmune encephalomyelitis.J. Immunol.20141921597210.4049/jimmunol.1301513 24323580
    [Google Scholar]
  19. Van RompaeyL. GalienR. van der AarE.M. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases.J. Immunol.201319173568357710.4049/jimmunol.1201348 24006460
    [Google Scholar]
  20. AlhazzaniK. AhmadS.F. Al-HarbiN.O. Pharmacological inhibition of STAT3 by Stattic Ameliorates clinical symptoms and reduces autoinflammation in myeloid, lymphoid, and neuronal tissue compartments in relapsing-remitting model of experimental autoimmune encephalomyelitis in SJL/J Mice.Pharmaceutics202113792510.3390/pharmaceutics13070925 34206429
    [Google Scholar]
  21. PanwarV. SinghA. BhattM. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal Transduct. Target. Ther.20238137510.1038/s41392‑023‑01608‑z 37779156
    [Google Scholar]
  22. Dello RussoC. LisiL. FeinsteinD.L. NavarraP. mTOR kinase, a key player in the regulation of glial functions: Relevance for the therapy of multiple sclerosis.Glia201361330131110.1002/glia.22433 23044764
    [Google Scholar]
  23. VakrakouA.G. AlexakiA. BriniaM.E. AnagnostouliM. StefanisL. StathopoulosP. The mTOR signaling pathway in multiple sclerosis; from animal models to human data.Int. J. Mol. Sci.20222315807710.3390/ijms23158077 35897651
    [Google Scholar]
  24. FigliaG. GerberD. SuterU. Myelination and mTOR.Glia201866469370710.1002/glia.23273
    [Google Scholar]
  25. GiacoppoS. PollastroF. GrassiG. BramantiP. MazzonE. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis.Fitoterapia2017116778410.1016/j.fitote.2016.11.010 27890794
    [Google Scholar]
  26. BuonvicinoD. PratesiS. RanieriG. PistolesiA. GuastiD. ChiarugiA. The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis.Neurobiol. Dis.202419110638710.1016/j.nbd.2023.106387 38142841
    [Google Scholar]
  27. HouH. CaoR. QuanM. Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways.J. Neuroimmunol.2018324263410.1016/j.jneuroim.2018.08.012 30205205
    [Google Scholar]
  28. LuoW. XuH. XuL. Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation.Glia202371228430410.1002/glia.24271 36089914
    [Google Scholar]
  29. HouH. MiaoJ. CaoR. Rapamycin ameliorates experimental autoimmune encephalomyelitis by suppressing the mTOR-STAT3 pathway.Neurochem. Res.201742102831284010.1007/s11064‑017‑2296‑7 28600752
    [Google Scholar]
  30. ChinettiG. FruchartJ.C. StaelsB. Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation.Inflamm. Res.2000491049750510.1007/s000110050622 11089900
    [Google Scholar]
  31. LuconiM. CantiniG. SerioM. Peroxisome proliferator-activated receptor gamma (PPARγ): Is the genomic activity the only answer?Steroids2010758-958559410.1016/j.steroids.2009.10.012 19900469
    [Google Scholar]
  32. MalS. DwivediA.R. KumarV. KumarN. KumarB. KumarV. Role of peroxisome proliferator-activated receptor gamma (PPARγ) in different disease states: Recent updates.Curr. Med. Chem.202128163193321510.2174/1875533XMTA4rMjACx 32674727
    [Google Scholar]
  33. StorerP.D. XuJ. ChavisJ. DrewP.D. Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: Implications for multiple sclerosis.J. Neuroimmunol.20051611-211312210.1016/j.jneuroim.2004.12.015 15748950
    [Google Scholar]
  34. ValléeA. ValléeJ.N. GuillevinR. LecarpentierY. Interactions between the canonical WNT/beta-catenin pathway and PPAR gamma on neuroinflammation, demyelination, and remyelination in multiple sclerosis.Cell. Mol. Neurobiol.201838478379510.1007/s10571‑017‑0550‑9 28905149
    [Google Scholar]
  35. ValléeA. LecarpentierY. GuillevinR. ValléeJ.N. Demyelination in multiple sclerosis: Reprogramming energy metabolism and potential PPARγ agonist treatment approaches.Int. J. Mol. Sci.2018194121210.3390/ijms19041212 29659554
    [Google Scholar]
  36. DunnS.E. BhatR. StrausD.S. Peroxisome proliferator–activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity.J. Exp. Med.201020781599160810.1084/jem.20091663 20624891
    [Google Scholar]
  37. FakanB. SzalardyL. VecseiL. Exploiting the therapeutic potential of endogenous immunomodulatory systems in multiple sclerosis-special focus on the peroxisome proliferator-activated receptors (PPARs) and the kynurenines.Int. J. Mol. Sci.201920242610.3390/ijms20020426 30669473
    [Google Scholar]
  38. HuckeS. FloßdorfJ. GrützkeB. Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor γ.Brain201213551586160510.1093/brain/aws058 22447120
    [Google Scholar]
  39. ChoiJ.M. BothwellA.L.M. The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases.Mol. Cells201233321722210.1007/s10059‑012‑2297‑y 22382683
    [Google Scholar]
  40. RackeM.K. GockeA.R. MuirM. DiabA. DrewP.D. Lovett-RackeA.E. Nuclear receptors and autoimmune disease: The potential of PPAR agonists to treat multiple sclerosis.J. Nutr.2006136370070310.1093/jn/136.3.700 16484546
    [Google Scholar]
  41. SmithE.S. PorterfieldJ.E. KannanR.M. Leveraging the interplay of nanotechnology and neuroscience: Designing new avenues for treating central nervous system disorders.Adv. Drug Deliv. Rev.201914818120310.1016/j.addr.2019.02.009 30844410
    [Google Scholar]
  42. SiddiquiL. MishraH. TalegaonkarS. RaiM. Nanoformulations: Opportunities and challenges.In: Nanoformulations in Human Health: Challenges and Approaches.Springer202031210.1007/978‑3‑030‑41858‑8_1
    [Google Scholar]
  43. PottooF.H. SharmaS. JavedM.N. Lipid-based nanoformulations in the treatment of neurological disorders.Drug Metab. Rev.202052118520410.1080/03602532.2020.1726942 32116044
    [Google Scholar]
  44. ChenthamaraD. SubramaniamS. RamakrishnanS.G. Therapeutic efficacy of nanoparticles and routes of administration.Biomater. Res.20192312010.1186/s40824‑019‑0166‑x 31832232
    [Google Scholar]
  45. OjhaS. KumarB. ChadhaH. Neuroprotective potential of Dimethyl Fumarate-loaded polymeric nanoparticles against multiple sclerosis.Indian J. Pharm. Sci.201981310.36468/pharmaceutical‑sciences.535
    [Google Scholar]
  46. GhalamfarsaG. Hojjat-FarsangiM. Mohammadnia-AfrouziM. Application of nanomedicine for crossing the blood–brain barrier: Theranostic opportunities in multiple sclerosis.J. Immunotoxicol.201613560361910.3109/1547691X.2016.1159264 27416019
    [Google Scholar]
  47. DamavandiA.R. MirmosayyebO. EbrahimiN. Advances in nanotechnology versus stem cell therapy for the theranostics of multiple sclerosis disease.Appl. Nanosci.20231364043407310.1007/s13204‑022‑02698‑x
    [Google Scholar]
  48. PathakR. AfaqA. BlondeL. Thiazolidinediones in the treatment of managed care patients with type 2 diabetes.Am. J. Manag. Care2002816Suppl.S483S494 12408411
    [Google Scholar]
  49. LiY. ZhuZ.Y. LuB.W. Rosiglitazone ameliorates tissue plasminogen activator‐induced brain hemorrhage after stroke.CNS Neurosci. Ther.201925121343135210.1111/cns.13260 31756041
    [Google Scholar]
  50. ShaoZ.Q. LiuZ.J. Neuroinflammation and neuronal autophagic death were suppressed via Rosiglitazone treatment: New evidence on neuroprotection in a rat model of global cerebral ischemia.J. Neurol. Sci.20153491-2657110.1016/j.jns.2014.12.027 25623802
    [Google Scholar]
  51. NelsonM.L. PfeiferJ.A. HickeyJ.P. CollinsA.E. KalischB.E. Exploring Rosiglitazone’s potential to treat Alzheimer’s disease through the modulation of brain-derived neurotrophic factor.Biology2023127104210.3390/biology12071042 37508471
    [Google Scholar]
  52. SanY.Z. LiuY.U. ZhangY.U. ShiP.P. ZhuY.U.L.A.N. Peroxisome proliferator-activated receptor-γ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus.Mol. Med. Rep.20151221877188310.3892/mmr.2015.3641 25891824
    [Google Scholar]
  53. ParkE.J. ParkS.Y. JoeE. JouI. 15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia.J. Biol. Chem.200327817147471475210.1074/jbc.M210819200 12584205
    [Google Scholar]
  54. ChenY.C. WuJ.S. TsaiH.D. Peroxisome proliferator-activated receptor gamma (PPAR-γ) and neurodegenerative disorders.Mol. Neurobiol.201246111412410.1007/s12035‑012‑8259‑8 22434581
    [Google Scholar]
  55. MörklS. ButlerM.I. HollA. CryanJ.F. DinanT.G. Probiotics and the microbiota-gut-brain axis: Focus on psychiatry.Curr. Nutr. Rep.20209317118210.1007/s13668‑020‑00313‑5 32406013
    [Google Scholar]
  56. MorshediM. HashemiR. MoazzenS. SahebkarA. HosseinifardE.S. Immunomodulatory and anti-inflammatory effects of probiotics in multiple sclerosis: A systematic review.J. Neuroinflammation201916123110.1186/s12974‑019‑1611‑4 31752913
    [Google Scholar]
  57. KumarN. SahooN.K. MehanS. verma B. The importance of gut-brain axis and use of probiotics as a treatment strategy for multiple sclerosis.Mult. Scler. Relat. Disord.20237110454710.1016/j.msard.2023.104547 36805171
    [Google Scholar]
  58. JiangJ. ChuC. WuC. Efficacy of probiotics in multiple sclerosis: A systematic review of preclinical trials and meta-analysis of randomized controlled trials.Food Funct.20211262354237710.1039/D0FO03203D 33629669
    [Google Scholar]
  59. SalamiM. KouchakiE. AsemiZ. TamtajiO.R. How probiotic bacteria influence the motor and mental behaviors as well as immunological and oxidative biomarkers in multiple sclerosis? A double blind clinical trial.J. Funct. Foods20195281310.1016/j.jff.2018.10.023
    [Google Scholar]
  60. AsghariK.M. DolatkhahN. AyromlouH. MirnasiriF. DadfarT. HashemianM. The effect of probiotic supplementation on the clinical and para-clinical findings of multiple sclerosis: a randomized clinical trial.Sci. Rep.20231311857710.1038/s41598‑023‑46047‑6 37903945
    [Google Scholar]
  61. SadeghirashedS. KazemiF. TaheriS. EbrahimiM.T. ArastehJ. A novel probiotic strain exerts therapeutic effects on mouse model of multiple sclerosis by altering the expression of inflammasome and IDO genes and modulation of T helper cytokine profile.Metab. Brain Dis.202237119720710.1007/s11011‑021‑00857‑7 34757579
    [Google Scholar]
  62. SamaniS.A. MoloudiM.R. RamezanzadehR. Oral Administration of Probiotic Enterococcus durans to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice.Basic Clin. Neurosci.2022131354610.32598/bcn.2021.1955.1 36589015
    [Google Scholar]
  63. PathanA.R. GaikwadA.B. ViswanadB. RamaraoP. Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats.Eur. J. Pharmacol.20085891-317617910.1016/j.ejphar.2008.06.016 18602098
    [Google Scholar]
  64. ShahsavarianA. JavadiS. JahanabadiS. Antidepressant-like effect of atorvastatin in the forced swimming test in mice: The role of PPAR-gamma receptor and nitric oxide pathway.Eur. J. Pharmacol.2014745525810.1016/j.ejphar.2014.10.004 25446923
    [Google Scholar]
  65. SadaghianiM.S. Javadi-PaydarM. GharedaghiM.H. FardY.Y. DehpourA.R. Antidepressant-like effect of pioglitazone in the forced swimming test in mice: The role of PPAR-gamma receptor and nitric oxide pathway.Behav. Brain Res.2011224233634310.1016/j.bbr.2011.06.011 21704657
    [Google Scholar]
  66. KumarN. TyagiN. MehanS. SinghA.P. Formulation of solid lipid nanoparticles loaded with Rosiglitazone and Probiotic: Optimization and In-vitro characterization.Recent Pat. Nanotechnol.202418452754210.2174/0118722105268801231203144554 38305310
    [Google Scholar]
  67. KapoorT. MehanS. SuriM. Forskolin, an Adenylcyclase/] cAMP/CREB signaling activator restoring Myelin-associated oligodendrocyte destruction in experimental ethidium bromide model of multiple sclerosis.Cells20221118277110.3390/cells11182771 36139346
    [Google Scholar]
  68. UpadhayayS. MehanS. PrajapatiA. Nrf2/HO-1 signaling stimulation through Acetyl-11-Keto-Beta-Boswellic acid (AKBA) provides neuroprotection in ethidium bromide-induced experimental model of multiple sclerosis.Genes (Basel)2022138132410.3390/genes13081324 35893061
    [Google Scholar]
  69. KheraR. MehanS. BhallaS. Guggulsterone mediated JAK/STAT and PPAR-Gamma modulation prevents neurobehavioral and neurochemical abnormalities in propionic acid-induced experimental model of autism.Molecules202227388910.3390/molecules27030889 35164154
    [Google Scholar]
  70. KumarN. SharmaN. KheraR. GuptaR. MehanS. Guggulsterone ameliorates ethidium bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain.Metab. Brain Dis.202136591192510.1007/s11011‑021‑00691‑x 33635478
    [Google Scholar]
  71. SharmaN. UpadhayayS. ShandilyaA. Neuroprotection by solanesol against ethidium bromide-induced multiple sclerosis-like neurobehavioral, molecular, and neurochemical alterations in experimental rats.Phytomedicine Plus20211410005110.1016/j.phyplu.2021.100051
    [Google Scholar]
  72. SinghA. UpadhayayS. MehanS. Inhibition of c-JNK/p38MAPK signaling pathway by Apigenin prevents neurobehavioral and neurochemical defects in ethidium bromide-induced experimental model of multiple sclerosis in rats: Evidence from CSF, blood plasma and brain samples.Phytomedicine Plus20211410013910.1016/j.phyplu.2021.100139
    [Google Scholar]
  73. GoudarzvandM. JavanM. Mirnajafi-ZadehJ. MozafariS. TiraihiT. Vitamins E and D3 attenuate demyelination and potentiate remyelination processes of hippocampal formation of rats following local injection of ethidium bromide.Cell. Mol. Neurobiol.201030228929910.1007/s10571‑009‑9451‑x 19768531
    [Google Scholar]
  74. ShandilyaA. MehanS. KumarS. Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity.Molecules20222712387810.3390/molecules27123878 35745001
    [Google Scholar]
  75. YadavR.K. MehanS. SahuR. Protective effects of apigenin on methylmercury-induced behavioral/neurochemical abnormalities and neurotoxicity in rats.Hum. Exp. Toxicol.20224110.1177/09603271221084276 35373622
    [Google Scholar]
  76. RahiS. GuptaR. SharmaA. MehanS. Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism.Hum. Exp. Toxicol.202140111880189810.1177/09603271211013456 33906504
    [Google Scholar]
  77. MinjE. UpadhayayS. MehanS. Nrf2/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated neuroprotection in methyl mercury-induced experimental model of aLS.Neurochem. Res.202146112867288410.1007/s11064‑021‑03366‑2 34075522
    [Google Scholar]
  78. RajkhowaB. MehanS. SethiP. Activating SIRT-1 signalling with the mitochondrial-CoQ10 activator Solanesol improves neurobehavioral and neurochemical defects in Ouabain-induced experimental model of bipolar disorder.Pharmaceuticals (Basel)202215895910.3390/ph15080959 36015107
    [Google Scholar]
  79. BergadanoA. AmenE.M. JacobsenB. A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs.J. Biol. Methods201961110.14440/jbm.2019.265 31453257
    [Google Scholar]
  80. BhallaS. MehanS. 4-hydroxyisoleucine mediated IGF-1/GLP-1 signalling activation prevents propionic acid-induced autism-like behavioural phenotypes and neurochemical defects in experimental rats.Neuropeptides20229610229610.1016/j.npep.2022.102296 36307249
    [Google Scholar]
  81. SahuR. MehanS. KumarS. Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats.Toxicol. Rep.2022997799810.1016/j.toxrep.2022.04.023 35783250
    [Google Scholar]
  82. ChhabraS. MehanS. KhanZ. GuptaG.D. NarulaA.S. Matrine mediated neuroprotective potential in experimental multiple sclerosis: Evidence from CSF, blood markers, brain samples and in-silico investigations.J. Neuroimmunol.202338457820010.1016/j.jneuroim.2023.578200 37774554
    [Google Scholar]
  83. LotfiA. SoleimaniM. GhasemiN. Astaxanthin reduces demyelination and oligodendrocytes death in a rat model of multiple sclerosis.Cell J.202122456557110.22074/2Fcellj.2021.6999 32347051
    [Google Scholar]
  84. TsaoS.P. NurrahmaB.A. KumarR. Probiotic enhancement of antioxidant capacity and alterations of gut microbiota composition in 6-hydroxydopamin-induced parkinson’s disease rats.Antioxidants20211011182310.3390/antiox10111823 34829694
    [Google Scholar]
  85. HaoZ. WangW. GuoR. LiuH. Faecalibacterium prausnitzii (ATCC 27766) has preventive and therapeutic effects on chronic unpredictable mild stress-induced depression-like and anxiety-like behavior in rats.Psychoneuroendocrinology201910413214210.1016/j.psyneuen.2019.02.025 30844607
    [Google Scholar]
  86. TiwariA. KheraR. RahiS. Neuroprotective effect of α-Mangostin in Ameliorating Propionic Acid-Induced experimental model of autism in wistar rats.Brain Sci.202111328810.3390/brainsci11030288 33669120
    [Google Scholar]
  87. JadaunK.S. MehanS. SharmaA. SiddiquiE.M. KumarS. AlsuhaymiN. Neuroprotective effect of Chrysophanol as a PI3K/] AKT/mTOR signaling inhibitor in an experimental model of autologous blood-induced intracerebral hemorrhage.Curr. Med. Sci.202242224926610.1007/s11596‑022‑2496‑x 35079960
    [Google Scholar]
  88. AlbekairiT.H. KamraA. BhardwajS. Beta-boswellic acid reverses 3-Nitropropionic Acid-induced molecular, mitochondrial, and histopathological defects in experimental rat model of Huntington’s disease.Biomedicines20221011286610.3390/biomedicines10112866 36359390
    [Google Scholar]
  89. AdelusiT.I. OyedeleA.Q.K. BoyenleI.D. Molecular modeling in drug discovery.Informatics in Medicine Unlocked20222910088010.1016/j.imu.2022.100880
    [Google Scholar]
  90. KumarS. AbbasF. AliI. Integrated network pharmacology and in-silico approaches to decipher the pharmacological mechanism of Selaginella tamariscina in the treatment of non-small cell lung cancer.Phytomedicine Plus20233210041910.1016/j.phyplu.2023.100419
    [Google Scholar]
  91. ZakM. HananE.J. LupardusP. Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling.Bioorg. Med. Chem. Lett.201929121522153110.1016/j.bmcl.2019.04.008 30981576
    [Google Scholar]
  92. HuT. YehJ.E. PinelloL. Impact of the N-terminal domain of STAT3 in STAT3-Dependent transcriptional activity.Mol. Cell. Biol.202335193284330010.1128/MCB.00060‑15
    [Google Scholar]
  93. YangH. RudgeD.G. KoosJ.D. VaidialingamB. YangH.J. PavletichN.P. mTOR kinase structure, mechanism and regulation.Nature2013497744821722310.1038/nature12122 23636326
    [Google Scholar]
  94. NolteR.T. WiselyG.B. WestinS. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-γ.Nature1998395669813714310.1038/25931
    [Google Scholar]
  95. CosconatiS. ForliS. PerrymanA.L. HarrisR. GoodsellD.S. OlsonA.J. Virtual screening with AutoDock: Theory and practice.Expert Opin. Drug Discov.20105659760710.1517/17460441.2010.484460
    [Google Scholar]
  96. MorrisG.M. HueyR. LindstromW. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.J. Comput. Chem.200930162785279110.1002/jcc.21256 19399780
    [Google Scholar]
  97. O’BoyleN.M. BanckM. JamesC.A. MorleyC. VandermeerschT. HutchisonG.R. Open Babel: An open chemical toolbox.J. Cheminform.2011313310.1186/1758‑2946‑3‑33 21982300
    [Google Scholar]
  98. DallakyanS. OlsonA.J. Small-molecule library screening by docking with PyRx.Methods Mol. Biol.2015126324325010.1007/978‑1‑4939‑2269‑7_19 25618350
    [Google Scholar]
  99. KumarS. SenguptaS. AliI. Identification and exploration of quinazoline-1,2,3-triazole inhibitors targeting EGFR in lung cancer.J. Biomol. Struct. Dyn.20234121113531137210.1080/07391102.2023.2204360
    [Google Scholar]
  100. ReynoldsR. RoncaroliF. NicholasR. RadotraB. GvericD. HowellO. The neuropathological basis of clinical progression in multiple sclerosis.Acta Neuropathol.2011122215517010.1007/s00401‑011‑0840‑0 21626034
    [Google Scholar]
  101. GeurtsJ.J.G. CalabreseM. FisherE. RudickR.A. Measurement and clinical effect of grey matter pathology in multiple sclerosis.Lancet Neurol.201211121082109210.1016/S1474‑4422(12)70230‑2 23153407
    [Google Scholar]
  102. JacksonS.J. LeeJ. NikodemovaM. FabryZ. DuncanI.D. Quantification of myelin and axon pathology during relapsing progressive experimental autoimmune encephalomyelitis in the Biozzi ABH mouse.J. Neuropathol. Exp. Neurol.200968661662510.1097/NEN.0b013e3181a41d23 19458548
    [Google Scholar]
  103. ’t HartB.A. Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis.Primate Biol.201961175810.5194/pb‑6‑17‑2019 32110715
    [Google Scholar]
  104. Serra-de-OliveiraN. BoilesenS.N. Prado de França CarvalhoC. Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans.Behav. Brain Res.201528726527510.1016/j.bbr.2015.03.038 25843560
    [Google Scholar]
  105. GloudinaMH MogamatSH RajivTE TandiM The haematological profile of patients with multiple sclerosis2012http://www.scirp.org/journal/PaperInformation.aspx?PaperID=21173
    [Google Scholar]
  106. AkaishiT. MisuT. FujiharaK. White blood cell count profiles in multiple sclerosis during attacks before the initiation of acute and chronic treatments.Sci. Rep.20211112235710.1038/s41598‑021‑01942‑8 34785750
    [Google Scholar]
  107. ManoochehrabadiS. Arsang-JangS. MazdehM. InokoH. SayadA. TaheriM. Analysis of STAT1, STAT2 and STAT3 mRNA expression levels in the blood of patients with multiple sclerosis.Hum. Antibodies2019272919810.3233/HAB‑180352 30412483
    [Google Scholar]
  108. MaieseK. Novel insights for multiple sclerosis and demyelinating disorders with apoptosis, autophagy, FoxO, and mTOR.Curr. Neurovasc. Res.202118216917110.2174/1567202618999210505124235 33964865
    [Google Scholar]
  109. SzalardyL. ZadoriD. TanczosE. Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis.Neurosci. Lett.201355413113410.1016/j.neulet.2013.08.069 24021801
    [Google Scholar]
  110. FeinsteinD.L. GaleaE. GavrilyukV. Peroxisome proliferator-activated receptor-γ agonists prevent experimental autoimmune encephalomyelitis.Ann. Neurol.200251669470210.1002/ana.10206 12112074
    [Google Scholar]
  111. Lebrun-JulienF. BachmannL. NorrménC. Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination.J. Neurosci.201434258432844810.1523/JNEUROSCI.1105‑14.2014 24948799
    [Google Scholar]
  112. SteelmanA.J. ZhouY. KoitoH. Activation of oligodendroglial Stat3 is required for efficient remyelination.Neurobiol. Dis.20169133634610.1016/j.nbd.2016.03.023 27060559
    [Google Scholar]
  113. KumarS. MehanS. NarulaA.S. Therapeutic modulation of JAK-STAT, mTOR, and PPAR-γ signaling in neurological dysfunctions.J. Mol. Med. (Berl.)20231011-294910.1007/s00109‑022‑02272‑6 36478124
    [Google Scholar]
  114. MartinsT.B. RoseJ.W. JaskowskiT.D. Analysis of proinflammatory and anti-inflammatory cytokine serum concentrations in patients with multiple sclerosis by using a multiplexed immunoassay.Am. J. Clin. Pathol.2011136569670410.1309/AJCP7UBK8IBVMVNR 22031307
    [Google Scholar]
  115. KallaurA.P. OliveiraS.R. SimãoA.N.C. Cytokine profile in patients with progressive multiple sclerosis and its association with disease progression and disability.Mol. Neurobiol.20175442950296010.1007/s12035‑016‑9846‑x 27023227
    [Google Scholar]
  116. BrambillaR. The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis.Acta Neuropathol.2019137575778310.1007/s00401‑019‑01980‑7 30847559
    [Google Scholar]
  117. TotukÖ. ArsoyE. TürkoğluR. Effects of neurocognitive rehabilitation on the levels of neurotransmitters and memory proteins in patients with multiple sclerosis.Experimed202313318719310.26650/experimed.1318122
    [Google Scholar]
  118. AkyuzE. CelikB.R. AslanF.S. SahinH. AngelopoulouE. Exploring the role of neurotransmitters in multiple sclerosis: An expanded review.ACS Chem. Neurosci.202314452755310.1021/acschemneuro.2c00589 36724132
    [Google Scholar]
  119. MolesL. DelgadoS. Gorostidi-AicuaM. Microbial dysbiosis and lack of SCFA production in a Spanish cohort of patients with multiple sclerosis.Front. Immunol.20221396076110.3389/fimmu.2022.960761 36325343
    [Google Scholar]
  120. MelbyeP. OlssonA. HansenT.H. SøndergaardH.B. Bang OturaiA. Short-chain fatty acids and gut microbiota in multiple sclerosis.Acta Neurol. Scand.2019139320821910.1111/ane.13045 30427062
    [Google Scholar]
  121. SaresellaM. MarventanoI. BaroneM. Alterations in circulating fatty acid are associated with gut microbiota dysbiosis and inflammation in multiple sclerosis.Front. Immunol.202011139010.3389/fimmu.2020.01390 32733460
    [Google Scholar]
  122. Martinez-AssucenaA. MarnetoftS.U. RoviraT.R. Hernandez-San-MiguelJ. BernabeuM. Martinell-Gispert-SauchM. Rehabilitation for multiple sclerosis in adults (I); Impairment and impact on functioning and quality of life: An overview.Crit. Rev. Phys. Rehabil. Med.2010221-410317810.1615/CritRevPhysRehabilMed.v22.i1‑4.90
    [Google Scholar]
  123. SchreckL. RyanS. MonaghanP. Cerebellum and cognition in multiple sclerosis.J. Neurophysiol.201812062707270910.1152/jn.00245.2018
    [Google Scholar]
  124. GoudarzvandM. ChoopaniS. ShamsA. Focal injection of ethidium bromide as a simple model to study cognitive deficit and its improvement.Basic Clin. Neurosci.2016716372 27303601
    [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273336107241015100912
Loading
/content/journals/cnsnddt/10.2174/0118715273336107241015100912
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test