PMID- 34445097
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210920
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 16
DP  - 2021 Aug 4
TI  - Reviewing the Significance of Blood-Brain Barrier Disruption in Multiple 
      Sclerosis Pathology and Treatment.
LID - 10.3390/ijms22168370 [doi]
LID - 8370
AB  - The disruption of blood-brain barrier (BBB) for multiple sclerosis (MS) 
      pathogenesis has a double effect: early on during the onset of the immune attack 
      and later for the CNS self-sustained 'inside-out' demyelination and 
      neurodegeneration processes. This review presents the characteristics of BBB 
      malfunction in MS but mostly highlights current developments regarding the 
      impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial 
      dysfunctions of the BBB's endothelial cells. The hypoxic hypothesis is largely 
      studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS 
      might be produced per se by the NVU malfunction or secondary to mitochondria 
      dysfunction. We present three different but related terms that denominate the 
      ongoing neurodegenerative process in progressive forms of MS that are indirectly 
      related to BBB disruption: progression independent of relapses, no evidence of 
      disease activity and smoldering demyelination or silent progression. Dimethyl 
      fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs 
      that are able to cross the BBB and exhibit beneficial direct effects in the CNS 
      with very different mechanisms of action, providing hope that a combined therapy 
      might be effective in treating MS. Detailed mechanisms of action of these DMTs 
      are described and also illustrated in dedicated images. With increasing knowledge 
      about the involvement of BBB in MS pathology, BBB might become a therapeutic 
      target in MS not only to make it impenetrable against activated immune cells but 
      also to allow molecules that have a neuroprotective effect in reaching the cell 
      target inside the CNS.
FAU - Balasa, Rodica
AU  - Balasa R
AD  - Department of Neurology, University of Medicine, Pharmacy, Sciences and 
      Technology "George Emil Palade", 540136 Targu Mures, Romania.
AD  - Neurology 1 Clinic, Emergency Clinical County Hospital Mures, 540136 Targu Mures, 
      Romania.
FAU - Barcutean, Laura
AU  - Barcutean L
AUID- ORCID: 0000-0002-3033-0583
AD  - Department of Neurology, University of Medicine, Pharmacy, Sciences and 
      Technology "George Emil Palade", 540136 Targu Mures, Romania.
AD  - Neurology 1 Clinic, Emergency Clinical County Hospital Mures, 540136 Targu Mures, 
      Romania.
FAU - Mosora, Oana
AU  - Mosora O
AD  - Neurology 1 Clinic, Emergency Clinical County Hospital Mures, 540136 Targu Mures, 
      Romania.
FAU - Manu, Doina
AU  - Manu D
AUID- ORCID: 0000-0001-8374-4977
AD  - Advanced Research Center Medical and Pharmaceutical, University of Medicine, 
      Pharmacy, Sciences and Technology "George Emil Palade", 540142 Targu Mures, 
      Romania.
LA  - eng
GR  - 10126/2/17.12.2020/Universitatea de Medicina, Farmacie, Stiinte si Tehnologie din 
      Targu Mures/
PT  - Journal Article
PT  - Review
DEP - 20210804
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/metabolism/*pathology
MH  - Disease Progression
MH  - Endothelial Cells/drug effects/metabolism/pathology
MH  - Humans
MH  - Mitochondria/drug effects/metabolism/pathology
MH  - Multiple Sclerosis/drug therapy/metabolism/*pathology
PMC - PMC8395058
OTO - NOTNLM
OT  - blood-brain barrier
OT  - disease modifying therapies progression
OT  - impermeability
OT  - multiple sclerosis
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/09/21 06:00
PMCR- 2021/08/04
CRDT- 2021/08/27 01:22
PHST- 2021/06/02 00:00 [received]
PHST- 2021/07/19 00:00 [revised]
PHST- 2021/07/31 00:00 [accepted]
PHST- 2021/08/27 01:22 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/08/04 00:00 [pmc-release]
AID - ijms22168370 [pii]
AID - ijms-22-08370 [pii]
AID - 10.3390/ijms22168370 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Aug 4;22(16):8370. doi: 10.3390/ijms22168370.