Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis

  title={Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis},
  author={Susie Leech and John Kirk and Jonathan Plumb and Stephen McQuaid},
  journal={Neuropathology and Applied Neurobiology},
Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood–brain barrier endothelium, in lesional and normal‐appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical… 
Blood-Brain Barrier Alterations in the Cerebral Cortex in Experimental Autoimmune Encephalomyelitis
Observations indicate that, in the cerebral cortex of EAE-affected mice, there is a microvascular disease that differentially targets claudin-5 and occludin during ongoing demyelination despite only minimal inflammation.
Vascular pathology in multiple sclerosis: reframing pathogenesis around the blood-brain barrier
The changes that occur in BBB function and cerebral perfusion in patients with MS are reviewed and genetic and environmental risk factors that, in addition to modulating immune function, may also converge to act on the vasculature are highlighted.
Blood–brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE
Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment
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.
Sera from Remitting and Secondary Progressive Multiple Sclerosis Patients Disrupt the Blood-Brain Barrier
The up-regulation of autocrine MMP-2/9 by BMECs after exposure to sera from RRMS-R patients or the autoantibodies against BM ECs from SPMS patients can compromise the BBB.
Blood-Brain Barrier Dysfunction and Cerebral Small Vessel Disease (Arteriolosclerosis) in Brains of Older People
It is suggested that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.
Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.
It is reported that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons, suggesting that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed.
Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination
It is demonstrated that brain‐derived MPCs respond to pathologic mechanisms involved in MS disease progression and suggest that vessel‐targeted therapeutics may benefit patients with progressive MS.
Blood–brain barrier dysfunction in immuno-mediated neurological diseases
The basic structure and cellular biology of the BBB is described, recent insights regarding the pathophysiology of theBBB breakdown in the setting of immuno-mediated neurological diseases are discussed, and the recent findings of autoantibody-mediated BBB breakdown are described.
Differences in expression of junctional adhesion molecule-A and β-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junction pathology
Altered expression of JAM-A, in addition to affecting junctional tightness may also both reflect and affect leukocyte trafficking, with implications for immune status within the diseased CNS.


Abnormal Endothelial Tight Junctions in Active Lesions and Normal‐appearing White Matter in Multiple Sclerosis
Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non‐enhancing focal and diffuse lesions in NAWM.
Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood–brain barrier leakage and active demyelination
It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage.
Blood‐Brain Barrier Abnormalities in Longstanding Multiple Sclerosis Lesions. An Immunohistochemical Study
  • E. KwonJ. Prineas
  • Biology, Medicine
    Journal of neuropathology and experimental neurology
  • 1994
The findings suggest that the blood-brain barrier (BBS) is permanently damaged in many old plaques, although to a degree not often detectable by current gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI).
Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis
The present findings in chronic silent multiple sclerosis lesions suggest that central nervous system endothelial cells show persistent abnormalities of the blood-brain barrier, even in the absence of active inflammation.
Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study.
The results suggest that the inflammatory changes in early MS plaques may have some specificity which could be related to the antigens whose presence is inferred by the colocation of complement and immunoglobulin on material within activated macrophages and astrocytes.
The blood-brain barrier in systemic lupus erythematosus
Evidence that damage to the brain endothelium forming the blood-brain barrier (BBB) is a contributoryfactor in systemic lupus erythematosus or NPSLE is summarized.
Severe alterations of endothelial and glial cells in the blood‐brain barrier of dystrophic mdx mice
The findings indicate that dystrophin deficiency in the mdx brain leads to severe injury of the endothelial and glial cells with disturbance in α‐actin cytoskeleton, ZO‐1, claudin‐ 1, and AQP4 assembly, as well as BBB breakdown.
Viral Infection at the Blood-Brain Barrier in Multiple Sclerosis: – An Ultrastructural Study of Tissues from a Uk Regional Brain Bank
An ultrastructural search for viruses was undertaken in the CNS microvasculature, in autopsy and biopsy tissue from human CNS primary demyelinating diseases, including MS, and it was concluded that the detection rate of such infections in pathological tissue could underestimate their true frequency.
Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme
The selective loss of claudin-3 from BBB TJs under pathological conditions such as EAE or GBM when the integrity of the BBB is compromised is demonstrated, and therefore it is suggested that claud in-3 is a central component determining the Integrity of BBB BJ TJs in vivo.