{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:45:31Z","timestamp":1791902731906,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Animal Ethics Committee (IAEC)","award":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"],"award-info":[{"award-number":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["ISFCP\/IAEC\/CPCSEA\/Meeting No.23\/2018\/Protocol No.389"],"award-info":[{"award-number":["ISFCP\/IAEC\/CPCSEA\/Meeting No.23\/2018\/Protocol No.389"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["RSP2022R491"],"award-info":[{"award-number":["RSP2022R491"]}]},{"name":"King Saud University","award":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"],"award-info":[{"award-number":["816\/PO\/ReBiBt\/S\/04\/CPCSEA"]}]},{"name":"King Saud University","award":["ISFCP\/IAEC\/CPCSEA\/Meeting No.23\/2018\/Protocol No.389"],"award-info":[{"award-number":["ISFCP\/IAEC\/CPCSEA\/Meeting No.23\/2018\/Protocol No.389"]}]},{"name":"King Saud University","award":["RSP2022R491"],"award-info":[{"award-number":["RSP2022R491"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic neurodegenerative disease marked by oligodendrocyte loss, which results in central neuronal demyelination. AC\/cAMP\/CREB signaling dysregulation is involved in the progression of MS, including mitochondrial dysfunctions, reduction in nerve growth factors, neuronal inflammation, apoptosis, and white matter degeneration. Our previous research has shown that Forskolin (FSK), a naturally occurring direct adenylyl cyclase (AC)\/cAMP\/CREB activator, has neuroprotective potential to alleviate pathogenic factors linked with numerous neurological abnormalities. The current study intends to explore the neuroprotective potential of FSK at doses of 40 mg\/kg and 60 mg\/kg alone, as well as in combination with conventional medicines, such as Fingolimod (FNG), Donepezil (DON), Memantine (MEM), and Simvastatin (SIM) in EB-induced demyelinated experimental MS rats. Adult Wistar rats were divided into nine groups, and EB was infused stereotaxically in the rat brain\u2019s intracerebropeduncle (ICP) area. Chronic gliotoxin EB treatment results in demyelination as well as motor and cognitive dysfunctions. FSK, combined with standard medications, improves behavioral dysfunctions, such as neuromuscular and motor deficits and memory and cognitive abnormalities. Following pharmacological treatments improved remyelination by enhancing myelin basic protein and increasing AC, cAMP, and CREB levels in brain homogenates. Furthermore, FSK therapy restored brain mitochondrial-ETC complex enzymes and neurotransmitter levels while decreasing inflammatory cytokines and oxidative stress markers. The Luxol fast blue (LFB) stain results further indicate FSK\u2019s neuroprotective potential in preventing oligodendrocyte death. Therefore, the results of these studies contribute to a better understanding of the possible role that natural phytochemicals FSK could have in preventing motor neuron diseases, such as multiple sclerosis.<\/jats:p>","DOI":"10.3390\/cells11182771","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T23:35:57Z","timestamp":1662420957000},"page":"2771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Forskolin, an Adenylcyclase\/cAMP\/CREB Signaling Activator Restoring Myelin-Associated Oligodendrocyte Destruction in Experimental Ethidium Bromide Model of Multiple Sclerosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Tarun","family":"Kapoor","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-835X","authenticated-orcid":false,"given":"Sidharth","family":"Mehan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Suri","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Acharan S.","family":"Narula","sequence":"additional","affiliation":[{"name":"Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-9826","authenticated-orcid":false,"given":"Abdulrahman","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7569-4287","authenticated-orcid":false,"given":"Abdullah F.","family":"Alasmari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metab","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-229X","authenticated-orcid":false,"given":"Mohammed A.","family":"Assiri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7764-3640","authenticated-orcid":false,"given":"Reni","family":"Kalfin","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, 1113 Sofia, Bulgaria"},{"name":"Department of Healthcare, South-West University \u201cNeofitRilski\u201d, Ivan Mihailov St. 66, 2700 Blagoevgrad, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","first-page":"969657","article-title":"Is multiple sclerosis an autoimmune disease?","volume":"2012","author":"Wootla","year":"2012","journal-title":"Autoimmune Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1097\/WCO.0000000000000622","article-title":"Multiple sclerosis: Clinical aspects","volume":"31","author":"Oh","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. Scler. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1177\/1756285613488434","article-title":"Sex and gender issues in multiple sclerosis","volume":"6","author":"Harbo","year":"2013","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.4103\/0972-2327.164814","article-title":"Epidemiology and genetic aspects of multiple sclerosis in India","volume":"18","author":"Bhatia","year":"2015","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100019","DOI":"10.1016\/j.dscb.2021.100019","article-title":"Targeting Nrf2\/HO-1 anti-oxidant signaling pathway in the progression of multiple sclerosis and influences on neurological dysfunctions","volume":"3","author":"Upadhayay","year":"2021","journal-title":"Brain Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/1570163817666200207100903","article-title":"Neuroprotective Methodologies in the Treatment of Multiple Sclerosis Current Status of Clinical and Pre-clinical Findings","volume":"18","author":"Mehan","year":"2021","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100139","DOI":"10.1016\/j.phyplu.2021.100139","article-title":"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","volume":"1","author":"Singh","year":"2021","journal-title":"Phytomed. Plus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100051","DOI":"10.1016\/j.phyplu.2021.100051","article-title":"Neuroprotection by solanesol against Ethidium Bromide-induced multiple sclerosis-like neurobehavioral, molecular, and neurochemical alterations in experimental rats","volume":"1","author":"Sharma","year":"2021","journal-title":"Phytomed. Plus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s11011-021-00691-x","article-title":"Guggulsterone ameliorates Ethidium Bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain","volume":"36","author":"Kumar","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3389\/fnmol.2018.00255","article-title":"cAMP Response Element-Binding Protein (CREB): A Possible Signaling Molecule Link in the Pathophysiology of Schizophrenia","volume":"11","author":"Wang","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"917527","DOI":"10.3389\/fneur.2022.917527","article-title":"A Brief Overview on BDNF-Trk Pathway in the Nervous System: A Potential Biomarker or Possible Target in Treatment of Multiple Sclerosis?","volume":"13","author":"Iacono","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3389\/fphar.2015.00161","article-title":"Global and local missions of cAMP signaling in neural plasticity, learning, and memory","volume":"6","author":"Lee","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s12035-014-8857-8","article-title":"Protective effect of a cAMP analogue on behavioral deficits and neuropathological changes in cuprizone model of demyelination","volume":"52","author":"Vakilzadeh","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-4889(98)00178-5","article-title":"Signal perception and transduction: The role of protein kinases","volume":"1449","author":"Schenk","year":"1999","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_16","first-page":"45","article-title":"Neuroprotective effect of ellagic acid against chronically scopolamine induced Alzheimer\u2019s type memory and cognitive dysfunctions: Possible behavioural and biochemical evidences","volume":"1","author":"Kaur","year":"2015","journal-title":"Int. J. Prev. Med. Res."},{"key":"ref_17","first-page":"144","article-title":"Role of adenylyl cyclase activator in controlling experimental diabetic nephropathy in rats","volume":"10","author":"Singh","year":"2018","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1573407216999200723113054","article-title":"Neuroprotective potential of adenylcyclase\/cAMP\/CREB and mitochondrial CoQ10 activator in amyotrophic lateral sclerosis rats","volume":"17","author":"Alam","year":"2021","journal-title":"Curr. Bioact. Compd."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mehan, S., Khera, H., and Sharma, R. (2019). Neuroprotective Strategies of Blood-Brain Barrier Penetrant \u201cForskolin\u201d (AC\/cAMP\/PK) to Ameliorate Mitochondrial Dysfunctioning in Neurotoxic Experimental Model of Autism. Recent Advances in Neurodegeneration, IntechOpen.","DOI":"10.5772\/intechopen.80046"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4103\/1673-5374.200812","article-title":"Adenylcyclase activator forskolin protects against Huntington\u2019s disease-like neurodegenerative disorders","volume":"12","author":"Mehan","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1016\/j.bbadis.2013.03.004","article-title":"Cyclophilin D deficiency rescues A\u03b2-impaired PKA\/CREB signaling and alleviates synaptic degeneration","volume":"1842","author":"Du","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fanara, S., Aprile, M., Iacono, S., Schir\u00f2, G., Bianchi, A., Brighina, F., Dominguez, L.J., Ragonese, P., and Salemi, G. (2021). The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review. Nutrients, 25.","DOI":"10.3390\/nu13113774"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2013.02.011","article-title":"Fingolimod: Direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy","volume":"328","author":"Groves","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"807639","DOI":"10.3389\/fphar.2022.807639","article-title":"Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod","volume":"13","author":"Pournajaf","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_25","first-page":"1444","article-title":"Fingolimod enhances oligodendrocyte differentiation of transplanted human induced pluripotent stem cell-derived neural progenitors","volume":"17","author":"Yazdi","year":"2018","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/cns.13035","article-title":"A review of clinical treatment considerations of donepezil in severe Alzheimer\u2019s disease","volume":"24","author":"Adlimoghaddam","year":"2018","journal-title":"CNS Neurosci. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s10020-018-0020-y","article-title":"Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia","volume":"24","author":"Han","year":"2018","journal-title":"Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.coph.2005.09.007","article-title":"Mechanism of action of memantine","volume":"6","author":"Johnson","year":"2006","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jns.2016.02.012","article-title":"Efficacy and safety profile of memantine in patients with cognitive impairment in multiple sclerosis: A randomized, placebo-controlled study","volume":"363","author":"Creveuil","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/mt.2015.69","article-title":"Anti-inflammatory therapy with simvastatin improves neuroinflammation and CNS function in a mouse model of metachromatic leukodystrophy","volume":"23","author":"Stein","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gupta, R., Mehan, S., Sethi, P., Prajapati, A., Alshammari, A., Alharbi, M., Al-Mazroua, H.A., and Narula, A.S. (2022). Smo-Shh agonist Purmorphamine prevents neurobehavioral and neurochemical defects in 8-OH-DPAT-induced experimental model of obsessive-compulsive disorder. Brain Sci., 12.","DOI":"10.3390\/brainsci12030342"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3233\/ADR-190125","article-title":"Neuroprotective approach of anti-cancer microtubule stabilizers against tauopathy associated dementia: Current status of clinical and preclinical findings","volume":"3","author":"Duggal","year":"2019","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105067","DOI":"10.1016\/j.neuint.2021.105067","article-title":"Targeting PI3K-AKT\/mTOR signaling in the prevention of autism","volume":"147","author":"Sharma","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.toxrep.2022.04.023","article-title":"Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats","volume":"9","author":"Sahu","year":"2022","journal-title":"Toxicol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Khera, R., Mehan, S., Bhalla, S., Kumar, S., Alshammari, A., Alharbi, M., and Sadhu, S.S. (2022). Guggulsterone mediated JAK\/STAT and PPAR-gamma modulation prevents neurobehavioral and neurochemical abnormalities in propionic acid-induced experimental model of autism. Molecules, 27.","DOI":"10.3390\/molecules27030889"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shandilya, A., Mehan, S., Kumar, S., Sethi, P., Narula, A.S., Alshammari, A., Alharbi, M., and Alasmari, A.F. (2022). Activation of IGF-1\/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity. Molecules, 27.","DOI":"10.3390\/molecules27123878"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ibror.2020.03.001","article-title":"Neuroprotective potential of solanesol in a combined model of intracerebral and intraventricular hemorrhage in rats","volume":"8","author":"Rajdev","year":"2020","journal-title":"IBRO Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.4103\/1673-5374.270316","article-title":"Adenylatecyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats","volume":"15","author":"Mehan","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.toxrep.2019.10.019","article-title":"Neuroprotective potential of solanesol in intracerebroventricular propionic acid induced experimental model of autism: Insights from behavioral and biochemical evidence","volume":"6","author":"Sharma","year":"2019","journal-title":"Toxicol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1007\/s11064-021-03366-2","article-title":"Nrf2\/HO-1 signaling activator acetyl-11-keto-beta Boswellic acid (AKBA)-Mediated Neuroprotection in Methyl Mercury-induced experimental model of ALS","volume":"46","author":"Minj","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.1016\/j.sjbs.2021.07.010","article-title":"Neuroprotective efficacy of 4-Hydroxyisoleucine in experimentally induced intracerebral hemorrhage","volume":"28","author":"Siddiqui","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1177\/09603271211013456","article-title":"Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism","volume":"40","author":"Rahi","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"09603271221084276","DOI":"10.1177\/09603271221084276","article-title":"Protective effects of apigenin on methylmercury-induced behavioral\/neurochemical abnormalities and neurotoxicity in rats","volume":"41","author":"Yadav","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0891-0618(03)00034-6","article-title":"6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates","volume":"26","author":"Maharaj","year":"2003","journal-title":"J. Chem. Neuroanat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"72881","DOI":"10.1039\/C5RA13160J","article-title":"Experimental evidence for the potential of lycopene in the management of scopolamine induced amnesia","volume":"5","author":"Bala","year":"2015","journal-title":"RSC Adv."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejphar.2009.08.027","article-title":"Amelioration of intracerebroventricularstreptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine\u2014A PDE1 inhibitor","volume":"620","author":"Deshmukh","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_47","first-page":"68","article-title":"Neuroprotection of brain permeable Forskolin ameliorates behavioral, biochemical and histopatho-logical alterations in rat model of intracerebral hemorrhage","volume":"10","author":"Dudi","year":"2018","journal-title":"Pharmaspire"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1007\/s12035-016-9891-5","article-title":"Resveratrol promotes remyelination in cuprizone model of multiple sclerosis: Biochemical and histological study","volume":"54","author":"Ghaiad","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1590\/S0100-879X2002000100014","article-title":"Ethidium Bromide-induced demyelination of the sciatic nerve of adult Wistar rats","volume":"35","author":"Fernandes","year":"2002","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_50","first-page":"63","article-title":"Focal injection of Ethidium Bromide as a simple model to study cognitive deficit and its improvement","volume":"7","author":"Goudarzvand","year":"2016","journal-title":"Basic Clin. Neurosci."},{"key":"ref_51","first-page":"981070","article-title":"Body mass index in multiple sclerosis: Associations with CSF neurotransmitter metabolite levels","volume":"2013","author":"Markianos","year":"2013","journal-title":"Int. Sch. Res. Not."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nprot.2006.116","article-title":"Morris water maze: Procedures for assessing spatial and related forms of learning and memory","volume":"1","author":"Vorhees","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/01.NPT.0000282260.59078.e4","article-title":"Locomotor training and virtual reality-based balance training for an individual with multiple sclerosis: A case report","volume":"29","author":"Fulk","year":"2005","journal-title":"J. Neurol. Phys. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"720856","DOI":"10.1155\/2015\/720856","article-title":"Cognitive-motor interference in multiple sclerosis: A systematic review of evidence, correlates, and consequences","volume":"2015","author":"Wajda","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1309\/AJCPCYCH96QYPHJM","article-title":"Cerebrospinal fluid myelin basic protein is frequently ordered but has little value: A test utilization study","volume":"138","author":"Greene","year":"2012","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Barcelos, I.P., Troxell, R.M., and Graves, J.S. (2019). Mitochondrial dysfunction and multiple sclerosis. Biology, 11.","DOI":"10.3390\/biology8020037"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2011.03.004","article-title":"Tumor necrosis factor alpha (TNF-\u03b1), anti-TNF-\u03b1 and demyelination revisited: An ongoing story","volume":"234","author":"Caminero","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jneuroim.2008.11.004","article-title":"The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: The elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy","volume":"15","author":"Dujmovic","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10735-018-9786-z","article-title":"Microglia polarization by methylprednizolone acetate accelerates cuprizone induced demyelination","volume":"49","author":"Noorzehi","year":"2018","journal-title":"J. Mol. Histol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/18\/2771\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:58Z","timestamp":1760142238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/18\/2771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,6]]},"references-count":59,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cells11182771"],"URL":"https:\/\/doi.org\/10.3390\/cells11182771","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,6]]}}}