Blood–brain barrier dysfunction in multiple sclerosis (improved by vitamin D, etc.) – Jan 2024

Blood–brain barrier dysfunction in multiple sclerosis: causes, consequences, and potential effects of therapies

Lancet January, 2024DOI:https://doi.org/10.1016/S1474-4422(23)00377-0 PDF behind paywall
Bettina Zierfuss, PhD, Catherine Larochelle, MD PhD, Prof Alexandre Prat, MD PhD

Summary
Established by brain endothelial cells, the blood–brain barrier (BBB) regulates the trafficking of molecules, restricts immune cell entry into the CNS, and has an active role in neurovascular coupling (the regulation of cerebral blood flow to support neuronal activity). In the early stages of multiple sclerosis, around the time of symptom onset, inflammatory BBB damage is accompanied by pathogenic immune cell infiltration into the CNS. In the later stages of multiple sclerosis, dysregulation of neurovascular coupling is associated with grey matter atrophy.
Genetic and environmental factors associated with multiple sclerosis, including

  • dietary habits,
  • the gut microbiome,
  • and vitamin D concentrations,

might contribute directly and indirectly to brain endothelial cell dysfunction. Damage to brain endothelial cells leads to an influx of deleterious molecules into the CNS, accelerating leakage across the BBB. Potential future therapeutic approaches might help to prevent BBB damage (eg, monoclonal antibodies targeting cell adhesion molecules and fibrinogen) and help to repair BBB dysfunction (eg, mesenchymal stromal cells) in people with multiple sclerosis.

101 References

1.Wengler K Ha J Syritsyna O et al.
Abnormal blood–brain barrier water exchange in chronic multiple sclerosis lesions: a preliminary study.
Magn Reson Imaging. 2020; 70: 126-133
Scopus (7)
2.Freedman MS Devonshire V Duquette P et al.
Treatment optimization in multiple sclerosis: Canadian MS Working Group recommendations.
Can J Neurol Sci. 2020; 47: 437-455
Scopus (52)
3.Ramaglia V Rojas O Naouar I Gommerman JL
The ins and outs of central nervous system inflammation—lessons learned from multiple sclerosis.
Annu Rev Immunol. 2021; 39: 199-226
Scopus (22)
4.Proulx ST Engelhardt B
Central nervous system zoning: how brain barriers establish subdivisions for CNS immune privilege and immune surveillance.
J Intern Med. 2022; 292: 47-67
Scopus (16)
5.Bell AH Miller SL Castillo-Melendez M Malhotra A
The neurovascular unit: effects of brain insults during the perinatal period.
Front Neurosci. 2020; 131452
Scopus (79)
6.Spencer JI Bell JS DeLuca GC
Vascular pathology in multiple sclerosis: reframing pathogenesis around the blood–brain barrier.
J Neurol Neurosurg Psychiatry. 2018; 89: 42-52
Scopus (89)
7.Munji RN Soung AL Weiner GA et al.
Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood–brain barrier dysfunction module.
Nat Neurosci. 2019; 22: 1892-1902
Scopus (166)
8.Abadier M Lyck R
Pathways across the blood–brain barrier.
in: Lyck R Enzmann G The blood–brain barrier and inflammation. Springer International Publishing, Cham2017: 187-211
9.Marchetti L Francisco D Soldati S et al.
ACKR1 favors transcellular over paracellular T-cell diapedesis across the blood–brain barrier in neuroinflammation in vitro.
Eur J Immunol. 2022; 52: 161-177
Scopus (8)
10.Broux B Zandee S Gowing E et al.
Interleukin-26, preferentially produced by TH17 lymphocytes, regulates CNS barrier function.
Neurol Neuroimmunol Neuroinflamm. 2020; 7: e870
Scopus (16)
11.Charabati M Grasmuck C Ghannam S et al.
DICAM promotes TH17 lymphocyte trafficking across the blood–brain barrier during autoimmune neuroinflammation.
Sci Transl Med. 2022; 14eabj0473
Scopus (18)
12.Fournier AP Tastet O Charabati M et al.
Single-cell transcriptomics identifies brain endothelium inflammatory networks in experimental autoimmune encephalomyelitis.
Neurol Neuroimmunol Neuroinflamm. 2022; 10e200046
13.Charabati M Zandee S Fournier AP et al.
MCAM+ brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4+ T lymphocytes.
Brain. 2023; 146: 1483-1495
Scopus (5)
14.Fournier AP Zandee S Charabati M et al.
CLMP promotes leukocyte migration across brain barriers in multiple sclerosis.
Neurol Neuroimmunol Neuroinflamm. 2022; 9e200022
Scopus (3)
15.Michel L Grasmuck C Charabati M et al.
Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers.
Sci Transl Med. 2019; 11eaaw0475
Scopus (38)
16.Wimmer I Tietz S Nishihara H et al.
PECAM-1 stabilizes blood–brain barrier integrity and favors paracellular T-cell diapedesis across the blood–brain barrier during neuroinflammation.
Front Immunol. 2019; 10: 711
Scopus (102)
17.Larochelle C Uphaus T Broux B et al.
EGFL7 reduces CNS inflammation in mouse.
Nat Commun. 2018; 9: 819
Scopus (29)
18.Goasdoué K Miller SM Colditz PB Björkman ST
Review: the blood–brain barrier; protecting the developing fetal brain.
Placenta. 2017; 54: 111-116
Scopus (89)
19.Delaney C Campbell M
The blood–brain barrier: insights from development and ageing.
Tissue Barriers. 2017; 5e1373897
Scopus (21)
20.Skillbäck T Blennow K Zetterberg H et al.
Sex differences in CSF biomarkers for neurodegeneration and blood–brain barrier integrity.
Alzheimers Dement (Amst). 2021; 13e12141
21.Stamatovic SM Martinez-Revollar G Hu A Choi J Keep RF Andjelkovic AV
Decline in Sirtuin-1 expression and activity plays a critical role in blood–brain barrier permeability in aging.
Neurobiol Dis. 2019; 126: 105-116
Scopus (80)
22.Li Y Xie L Huang T et al.
Aging Neurovascular unit and potential role of dna damage and repair in combating vascular and neurodegenerative disorders.
Front Neurosci. 2019; 13: 778
Scopus (3)
23.Dobi A Rosanaly S Devin A et al.
Advanced glycation end-products disrupt brain microvascular endothelial cell barrier: the role of mitochondria and oxidative stress.
Microvasc Res. 2021; 133104098
Scopus (19)
24.D'Souza A Burch A Dave KM et al.
Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells.
J Control Release. 2021; 338: 505-526
Scopus (52)
25.Baranzini SE Oksenberg JR
The genetics of multiple sclerosis: from 0 to 200 in 50 years.
Trends Genet. 2017; 33: 960-970
Scopus (136)
Summary
Full Text
Full Text PDF
26.Jeong H-W Diéguez-Hurtado R Arf H et al.
Single-cell transcriptomics reveals functionally specialized vascular endothelium in brain.
eLife. 2022; 11e57520
27.Mohammadhosayni M Khosrojerdi A Lorian K et al.
Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis.
BMC Neurol. 2020; 20: 218
Scopus (10)
28.Patsopoulos NA Baranzini SE Santaniello A et al.
Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.
Science. 2019; 365eaav7188
29.Logsdon AF Erickson MA Rhea EM Salameh TS Banks WA
Gut reactions: how the blood–brain barrier connects the microbiome and the brain.
Exp Biol Med (Maywood). 2018; 243: 159-165
Scopus (150)
30.Rhea EM Salameh TS Logsdon AF Hanson AJ Erickson MA Banks WA
blood–brain barriers in obesity.
AAPS J. 2017; 19: 921-930
Scopus (85)
31.Zhou X Baumann R Gao X et al.
Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course.
Cell. 2022; 185: 3467-3486
Scopus (46)
Summary
Full Text
Full Text PDF
32.Cantoni C Lin Q Dorsett Y et al.
Alterations of host–gut microbiome interactions in multiple sclerosis.
EBioMedicine. 2022; 76103798
Scopus (43)
Summary
Full Text
Full Text PDF
33.Bäcker-Koduah P Bellmann-Strobl J Scheel M et al.
vitamin D and disease severity in multiple sclerosis-baseline data from the randomized controlled trial (EVIDIMS).
Front Neurol. 2020; 11: 129
Scopus (11)
34.Cortese M Munger KL Martínez-Lapiscina EH et al.
vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT.
Neurology. 2020; 94: e1950-e1960
Scopus (31)
35.Hupperts R Smolders J Vieth R et al.
Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a.
Neurology. 2019; 93: e1906-e1916
Scopus (74)
36.Bjornevik K Cortese M Healy BC et al.
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis.
Science. 2022; 375: 296-301
Scopus (647)
37.Tengvall K Huang J Hellström C et al.
Molecular mimicry between anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk.
Proc Natl Acad Sci USA. 2019; 116: 16955-16960
Scopus (86)
38.Lanz TV Brewer RC Ho PP et al.
Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM.
Nature. 2022; 603: 321-327
Scopus (251)
39.Zhang N Zuo Y Jiang L Peng Y Huang X Zuo L
Epstein-Barr virus and neurological diseases.
Front Mol Biosci. 2022; 8816098
Scopus (40)
40.Montgomery S Hiyoshi A Burkill S Alfredsson L Bahmanyar S Olsson T
Concussion in adolescence and risk of multiple sclerosis.
Ann Neurol. 2017; 82: 554-561
Scopus (37)
41.Degelman ML Herman KM
Smoking and multiple sclerosis: a systematic review and meta-analysis using the Bradford Hill criteria for causation.
Mult Scler Relat Disord. 2017; 17: 207-216
Scopus (91)
Summary
Full Text
Full Text PDF
42.Wu S-Y Xing F Sharma S et al.
Nicotine promotes brain metastasis by polarizing microglia and suppressing innate immune function.
J Exp Med. 2020; 217e20191131
Scopus (48)
43.Oakes JM Fuchs RM Gardner JD Lazartigues E Yue X
Nicotine and the renin–angiotensin system.
Am J Physiol Regul Integr Comp Physiol. 2018; 315: R895-R906
Scopus (199)
44.Olsson T Barcellos LF Alfredsson L
Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis.
Nat Rev Neurol. 2017; 13: 25-36
Scopus (636)
45.Zhang SL Yue Z Arnold DM Artiushin G Sehgal A
A circadian clock in the blood–brain barrier regulates xenobiotic efflux.
Cell. 2018; 173: 130-139.e10
Scopus (131)
Summary
Full Text
Full Text PDF
46.Cuddapah VA Zhang SL Sehgal A
Regulation of the blood–brain barrier by circadian rhythms and sleep.
Trends Neurosci. 2019; 42: 500-510
Scopus (99)
Summary
Full Text
Full Text PDF
47.Artiushin G Zhang SL Tricoire H Sehgal A
Endocytosis at the Drosophila blood–brain barrier as a function for sleep.
eLife. 2018; 7e43326
Scopus (49)
48.Sun J Wu J Hua F Chen Y Zhan F Xu G
Sleep deprivation induces cognitive impairment by increasing blood–brain barrier permeability via CD44.
Front Neurol. 2020; 11563916
Scopus (22)
49.Nishihara H Perriot S Gastfriend BD et al.
Intrinsic blood–brain barrier dysfunction contributes to multiple sclerosis pathogenesis.
Brain. 2022; 145: 4334-4348
Scopus (24)
50.Filippi M Brück W Chard D et al.
Association between pathological and MRI findings in multiple sclerosis.
Lancet Neurol. 2019; 18: 198-210
Scopus (144)
Summary
Full Text
Full Text PDF
51.Yong HYF Yong VW
Mechanism-based criteria to improve therapeutic outcomes in progressive multiple sclerosis.
Nat Rev Neurol. 2022; 18: 40-55
Scopus (40)
52.Petersen MA Ryu JK Akassoglou K
Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics.
Nat Rev Neurosci. 2018; 19: 283-301
Scopus (256)
53.Yates RL Esiri MM Palace J Jacobs B Perera R DeLuca GC
Fibrin(ogen) and neurodegeneration in the progressive multiple sclerosis cortex.
Ann Neurol. 2017; 82: 259-270
Scopus (77)
54.Ryu JK Rafalski VA Meyer-Franke A et al.
Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.
Nat Immunol. 2018; 19: 1212-1223
Scopus (118)
55.Willis CM Nicaise AM Menoret A et al.
Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis.
Proc Natl Acad Sci USA. 2019; 116: 10488-10493
Scopus (30)
56.Brailoiu E Shipsky MM Yan G Abood ME Brailoiu GC
Mechanisms of modulation of brain microvascular endothelial cells function by thrombin.
Brain Res. 2017; 1657: 167-175
Scopus (40)
57.Suthiphosuwan S Sati P Absinta M et al.
Paramagnetic rim sign in radiologically isolated syndrome.
JAMA Neurol. 2020; 77: 653-655
Scopus (32)
58.Hagemeier J Ramanathan M Schweser F et al.
Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals.
Neuroimage Clin. 2017; 17: 530-540
Scopus (27)
59.Sweeney MD Zhao Z Montagne A Nelson AR Zlokovic BV
blood–brain barrier: from physiology to disease and back.
Physiol Rev. 2019; 99: 21-78
Scopus (1043)
60.Benedict RHB Amato MP DeLuca J Geurts JJG
Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues.
Lancet Neurol. 2020; 19: 860-871
Scopus (237)
Summary
Full Text
Full Text PDF
61.Granziera C Wuerfel J Barkhof F et al.
Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis.
Brain. 2021; 144: 1296-1311
Scopus (58)
62.Sivakolundu DK West KL Maruthy GB et al.
Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis.
Mult Scler. 2020; 26: 1486-1496
Scopus (13)
63.Barro C Benkert P Disanto G et al.
Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis.
Brain. 2018; 141: 2382-2391
Scopus (300)
64.Uher T McComb M Galkin S et al.
Neurofilament levels are associated with blood–brain barrier integrity, lymphocyte extravasation, and risk factors following the first demyelinating event in multiple sclerosis.
Mult Scler. 2021; 27: 220-231
Scopus (41)
65.Sejbaek T Nielsen HH Penner N et al.
Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients.
J Neurol Neurosurg Psychiatry. 2019; 90: 1324-1330
66.Kuhle J Plavina T Barro C et al.
Neurofilament light levels are associated with long-term outcomes in multiple sclerosis.
Mult Scler. 2020; 26: 1691-1699
Scopus (57)
67.Hyun J-W Kim Y Kim G Kim S-H Kim HJ
Longitudinal analysis of serum neurofilament light chain: a potential therapeutic monitoring biomarker for multiple sclerosis.
Mult Scler. 2020; 26: 659-667
Scopus (21)
68.Sandelius Å Zetterberg H Blennow K et al.
Plasma neurofilament light chain concentration in the inherited peripheral neuropathies.
Neurology. 2018; 90: e518-e524
Scopus (162)
69.Kalm M Boström M Sandelius Å et al.
Serum concentrations of the axonal injury marker neurofilament light protein are not influenced by blood–brain barrier permeability.
Brain Res. 2017; 1668: 12-19
Scopus (44)
70.Watanabe M Nakamura Y Michalak Z et al.
Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD.
Neurology. 2019; 93: e1299-e1311
Scopus (112)
71.Papa L Ladde JG O'Brien JF et al.
Evaluation of glial and neuronal blood biomarkers compared with clinical decision rules in assessing the need for computed tomography in patients with mild traumatic brain injury.
JAMA Netw Open. 2022; 5e221302
Scopus (14)
72.Brambilla R
The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis.
Acta Neuropathol. 2019; 137: 757-783
Scopus (139)
73.Martinsen V Kursula P
Multiple sclerosis and myelin basic protein: insights into protein disorder and disease.
Amino Acids. 2022; 54: 99-109
Scopus (42)
74.Nohejlova H Kayserova J Capek V Toman T Krsek P Liba Z
Paediatric onset of multiple sclerosis: analysis of chemokine and cytokine levels in the context of the early clinical course.
Mult Scler Relat Disord. 2020; 46102467
Scopus (5)
Summary
Full Text
Full Text PDF
75.Wang D Duan H Feng J et al.
Soluble CD146, a cerebrospinal fluid marker for neuroinflammation, promotes blood–brain barrier dysfunction.
Theranostics. 2020; 10: 231-246
Scopus (21)
76.Ziliotto N Lamberti N Manfredini F et al.
Baseline and overtime variations of soluble adhesion molecule plasma concentrations are associated with mobility recovery after rehabilitation in multiple sclerosis patients.
J Neuroimmunol. 2021; 352577473
Scopus (2)
Summary
Full Text
Full Text PDF
77.Fournier AP Quenault A Martinez de Lizarrondo S et al.
Prediction of disease activity in models of multiple sclerosis by molecular magnetic resonance imaging of P-selectin.
Proc Natl Acad Sci USA. 2017; 114: 6116-6121
Scopus (37)
78.Masuda H Mori M Uchida T Uzawa A Ohtani R Kuwabara S
Soluble CD40 ligand contributes to blood–brain barrier breakdown and central nervous system inflammation in multiple sclerosis and neuromyelitis optica spectrum disorder.
J Neuroimmunol. 2017; 305: 102-107
Scopus (32)
Summary
Full Text
Full Text PDF
79.Agah E Zardoui A Saghazadeh A Ahmadi M Tafakhori A Rezaei N
Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: a systematic review and meta-analysis.
PLoS One. 2018; 13e0190252
Scopus (52)
80.Spitzer D Puetz T Armbrust M et al.
Anti-osteopontin therapy leads to improved edema and infarct size in a murine model of ischemic stroke.
Sci Rep. 2022; 1220925
Scopus (2)
81.Clemente N Comi C Raineri D et al.
Role of anti-osteopontin antibodies in multiple sclerosis and experimental autoimmune encephalomyelitis.
Front Immunol. 2017; 8: 321
Scopus (29)
82.Çiçekli E Sayan S Kotan D
Availability of fibrinogen/albumin ratio in MS attack.
Mult Scler Relat Disord. 2022; 60103674
Scopus (4)
Summary
Full Text
Full Text PDF
83.Miranda Acuña J Hidalgo de la Cruz M Ros AL Tapia SP Martínez Ginés ML de Andrés Frutos CD
Elevated plasma fibrinogen levels in multiple sclerosis patients during relapse.
Mult Scler Relat Disord. 2017; 18: 157-160
Scopus (17)
Summary
Full Text
Full Text PDF
84.Schaller-Paule MA Yalachkov Y Steinmetz H et al.
Analysis of CSF D-dimer to identify intrathecal fibrin-driven autoimmunity in patients with multiple sclerosis.
Neurol Neuroimmunol Neuroinflamm. 2022; 9e1150
Scopus (5)
85.Balasa R Barcutean L Mosora O Manu D
Reviewing the significance of blood–brain barrier disruption in multiple sclerosis pathology and treatment.
Int J Mol Sci. 2021; 228370
Scopus (40)
86.Pyka-Fosciak G Lis GJ Litwin JA
Effect of natalizumab treatment on metalloproteinases and their inhibitors in a mouse model of multiple sclerosis.
J Physiol Pharmacol. 2020; 71: 265-273
87.Knudsen MH Lindberg U Frederiksen JL et al.
blood–brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis.
Mult Scler Relat Disord. 2022; 63103891
Scopus (5)
Summary
Full Text
Full Text PDF
88.Nguyen K Juillard P Hawke S Grau GE Marsh-Wakefield F
Trans-endothelial migration of memory T Cells is impaired in alemtuzumab-treated multiple sclerosis patients.
J Clin Med. 2022; 116266
Scopus (1)
89.Ford RK Juillard P Hawke S Grau GE Marsh-Wakefield F
Cladribine reduces trans-endothelial migration of memory T cells across an in vitro blood–brain barrier.
J Clin Med. 2022; 116006
Scopus (4)
90.Sellebjerg F Blinkenberg M Sorensen PS
Anti-CD20 monoclonal antibodies for relapsing and progressive multiple sclerosis.
CNS Drugs. 2020; 34: 269-280
Scopus (42)
91.Krämer J Bar-Or A Turner TJ Wiendl H
Bruton tyrosine kinase inhibitors for multiple sclerosis.
Nat Rev Neurol. 2023; 19: 289-304
Scopus (9)
92.Banoth B Cassel SL
Bruton tyrosine kinase inhibition: clinical relevance beyond B cells.
J Allergy Clin Immunol. 2017; 140: 985-987
Scopus (8)
Summary
Full Text
Full Text PDF
93.Mizuno M Noto D Kaga N Chiba A Miyake S
The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models.
PLoS One. 2017; 12e0173032
Scopus (149)
94.Dai Y Wei T Shen Z Bei Y Lin H Dai H
Classical HDACs in the regulation of neuroinflammation.
Neurochem Int. 2021; 150105182
Scopus (16)
95.Shen Y Yang R Zhao J et al.
The histone deacetylase inhibitor belinostat ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting TLR2/MyD88 and HDAC3/NF-κB p65-mediated neuroinflammation.
Pharmacol Res. 2022; 176105969
Scopus (15)
96.Buonvicino D Ranieri G Chiarugi A
Treatment with non-specific HDAC inhibitors administered after disease onset does not delay evolution in a mouse model of progressive multiple sclerosis.
Neuroscience. 2021; 465: 38-45
Scopus (6)
Summary
Full Text
Full Text PDF
97.Ghaiad HR Nooh MM El-Sawalhi MM Shaheen AA
Resveratrol promotes remyelination in cuprizone model of multiple sclerosis: biochemical and histological study.
Mol Neurobiol. 2017; 54: 3219-3229
Scopus (85)
98.Boffa G Lapucci C Sbragia E et al.
Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab.
Eur J Neurol. 2020; 27: 2047-2055
Scopus (13)
99.Roudi S Rädler JA El Andaloussi S
Therapeutic potential of extracellular vesicles in neurodegenerative disorders.
Handb Clin Neurol. 2023; 193: 243-266
Scopus (0)
100.Hayakawa K Chan SJ Mandeville ET et al.
Protective effects of endothelial progenitor cell-derived extracellular mitochondria in brain endothelium.
Stem Cells. 2018; 36: 1404-1410
Scopus (91)
101.Charabati M Rabanel J-M Ramassamy C Prat A
Overcoming the brain barriers: from immune cells to nanoparticles.
Trends Pharmacol Sci. 2020; 41: 42-54
Scopus (27)

28,000 hits for "blood brain barrier" "vitamin d" in Google Scholar

https://scholar.google.com/scholar?hl=en&as_sdt=0%2C48&q=%22blood+brain+barrier%22+%22vitamin+d%22&btnG=|Google Scholar]

  • Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis- August 2017 https://doi.org/10.1111/cen3.12398 FREE PDF
  • Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications - June 2022 https://doi.org/10.1093/braincomms/fcac171 FREE PDF
    • "In this review, we focus on recent published data describing the biological effects of Vitamin D in animal models of multiple sclerosis on immune cells, blood–brain barrier function, activation of glial cells and its potential neuroprotective effects."
  • The Role of Vitamin D in Neuroprotection in Multiple Sclerosis: An Update - June 2023 https://doi.org/10.3390/nu15132978 FREE PDF
  • Intranasal administration of vitamin D attenuates blood–brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats - Oct 2016 https://doi.org/10.1177/0271678X16671147 FREE PDF
    • Note: VitaminDWiki has been successfully experimenting in inhaing Vitamin D since about 2015

VitaminDWiki – Multiple Sclerosis 32 percent less likely among those with more than 32 ng of vitamin D – Dec 2019

UV and Sunshine reduces MS risk

Other things also help

High Dose Vitamin D and cofactors

Number of MS studies which are also in other categories

  • 22 studies in Genetics - genes can restrict Vitamin D getting to the blood and to the cells
  • 14 studies in Vitamin D Receptor - gene which restricts D from getting to the cells
  • 7 studies in Vitamin D Binding Protein - gene which restricts D from getting to the cells
  • 21 studies in Ultraviolet light - may be even better than Vitamin D in preventing and treating MS
  • 9 studies in Omega-3 - which helps Vitamin D prevent and treat MS

See Brain in VitaminDWiki

See also in VitaminDWiki

VitaminDWiki – Overview MS and vitamin D contains

Clinical interventions have shown that Vitamin D can prevent, treat, and even cure Multiple Sclerosis, at a tiny fraction of the cost of the drugs now used to treat it, and without side effects.

Summary: lack of consensus on how much to prevent, treat, or cure MS.


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