SVOA Neurology Sera from Patients with Multiple Sclerosis in Relapse or Remission Affect the Blood-Brain Barrier Differently: An In vitro Study

Mathur, Manik; Gran, Bruno; Tanasescu, Radu; Constantinescu, Cris S; Bayraktutan, Ulvi; Bayraktutan, Ulvi

Abstract

Background: Breakdown of the blood-brain barrier (BBB) constitutes a key step in the pathogenesis of multiple sclerosis
(MS).
Aims: To investigate whether sera from MS patients in relapse or in remission may differently affect the BBB function
and to assesses the putative barrier-restorative effects of major molecular mechanisms known to regulate BBB function.
Methods: Sera were prepared by centrifugation of the whole blood samples of the study participants. A cell culture model
of human BBB, consisting of human brain microvascular endothelial cells, astrocytes and pericytes, was established
using transwell inserts. The integrity and function of BBB were studied by measurements of transendothelial electrical
resistance (TEER) and paracellular flux of Evan’s blue-labelled albumin (EBA), respectively.
Results: Sera from MS patients in relapse possessed greater levels of inflammatory cytokines (TNF- and IL-1 ), apoptotic
enzyme activity (caspase-3/7) and were more disruptive of BBB as evidenced by significant decreases in TEER and
increases in EBA flux. Suppression of intracellular availability of reactive oxygen species or NADPH oxidase, Rho -kinase,
protein kinase C-  and matrix metalloproteinase-2 activity by specific inhibitors markedly attenuated the BBBdisruptive
effects of sera obtained from MS patients in relapse or remission.
Conclusions: A plethora of mechanisms affecting the overall status of oxidative stress, inflammation, cell viability and
basement membrane integrity appear to contribute to the BBB damage in MS patients, especially those in relapse. Effective
inhibition of the key elements associated with these mechanisms mitigate the deleterious effects of MS patients’ sera
on BBB integrity and function.

Citation

Mathur, M., Gran, B., Tanasescu, R., Constantinescu, C. S., Bayraktutan, U., & Bayraktutan, U. (2022). SVOA Neurology Sera from Patients with Multiple Sclerosis in Relapse or Remission Affect the Blood-Brain Barrier Differently: An In vitro Study. SVOA Neurology, 3(5), 208-213

• Journal Article Type: Article
• Acceptance Date: Sep 7, 2022
• Online Publication Date: Sep 30, 2022
• Publication Date: Sep 30, 2022
• Deposit Date: Sep 30, 2022
• Publicly Available Date: Sep 30, 2022
• Journal: SVOA Neurology
• Print ISSN: 2753-9180
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 5
• Pages: 208-213
• Public URL: https://nottingham-repository.worktribe.com/output/11754489
• Publisher URL: https://sciencevolks.com/neurology/abstract/Sera-from-Patients-with-Multiple-Sclerosis-in-Relapse-or-Remission-Affect-the-Blood-Brain-Barrier-Differently-An-In-vitro-Study?id=MzUx