Sera from Patients with Multiple Sclerosis in Relapse or Remission Affect the Blood-Brain Barrier Differently: An In vitro Study
Manik Mathur1, Bruno Gran2, Radu Tanasescu2, Cris S. Constantinescu1,2,3 and Ulvi Bayraktutan1*
1Academic Unit of Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, UK
2Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK
3Department of Neurology, Cooper University, New Jersey, USA
*Corresponding Author: Dr. Ulvi Bayraktutan, Academic Unit of Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, UK.
Received: August 30, 2022 Published: September 20, 2022
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-α and IL-1 β), 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- β 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.
Keywords: blood-brain barrier; multiple sclerosis; inflammatory cytokines; apoptosis; rho-kinase; protein kinase C
Citation: Mathur M, Gran B, Tanasescu R, Constantinescu CS, Bayraktutan U. “Sera from Patients with Multiple Sclerosis in Relapse or Remission Affect the Blood-Brain Barrier Differently: An In vitro Study”. SVOA Neurology 2022, 3:5, 208-213.
