The Blood-Brain Barrier in Cortical Multiple Sclerosis Lesions

Abstract

The blood-brain barrier (BBB) is composed mainly of specialized endothelial cells characterized by the presence of intercellular tight junctions. Additionally, perivascular cells, astrocytes, and surrounding basement membranes determine BBB integrity. BBB disruption is an early phenomenon in the formation of new white matter multiple sclerosis (MS) lesions; however, knowledge of the extent of BBB changes in gray matter MS lesions is lacking. Here, we studied several markers for BBB integrity in well-characterized brain tissue of patients with MS. Plasma protein leakage was enhanced in white matter lesions compared with that in normal-appearing white matter, whereas plasma protein leakage was absent in gray matter lesions. White matter lesions showed irregular basement membranes and parenchymal depositions of collagen type IV, whereas purely gray matter lesions lacked basement membrane alterations. Similarly, we observed no evidence for astrogliosis and tight junction changes in cortical MS lesions. Although BBB dysfunction is a common feature of white matter MS lesions, cortical MS lesions lack markers for BBB disruption or astrogliosis. Our data may indicate that BBB breakdown is not a critical event in the formation of gray matter MS lesions.

Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome

“…36 These lesions are characterized pathologically by demyelination and microglial activation. 37,38 Therefore, compared with WM lesions, inflammation is not as prominent and breakdown of the blood-brain barrier occurs less frequently with GM lesions. 38 Assessment of cortical atrophy was proposed as an indirect marker of cortical pathologic assessment over time.…”

“…37,38 Therefore, compared with WM lesions, inflammation is not as prominent and breakdown of the blood-brain barrier occurs less frequently with GM lesions. 38 Assessment of cortical atrophy was proposed as an indirect marker of cortical pathologic assessment over time. 4 The use of advanced MR imaging sequences, such as double inversion recovery, 39 can enhance the detection of the number and volume of cortical lesions.…”

Functions of lipid raft membrane microdomains at the blood–brain barrier

“…The endothelial basement membrane and glia limitans formed by BECs and perivascular astrocyte end feet are composed of several extracellular matrix (ECM) components, including fibronectin, different laminin isoforms, collagen type IV, and heparan sulfate proteoglycans [11,55,70,71]. Its dense and compact nature provides the ability to function as a substrate for soluble protein immobilization and cell attachment.…”

“…Intercellular junctional complexes between brain endothelial cells (BECs), namely tight junctions (TJs) and adherens junctions (AJ), provide endothelial polarity in addition to high transendothelial electrical resistance (TEER) and restrictive permeability [5]. Pericytes and perivascular astrocytes, through complex communications and signaling events with BECs, induce BBB properties and promote TJ maintenance, specialized transporter expression, and immune quiescence of BECs [4,[6][7][8][9][10][11][12][13]. In the current review, we make use of the term BBB to include molecular and functional events, which occur at the level of the highly specialized capillaries and of postcapillary venules of the CNS.…”

Exploring the origins of grey matter damage in multiple sclerosis

“…Grey matter lesions are usually characterised by a relative lack of parenchymal lymphocyte infiltration, deposition of antibody and complement proteins, and blood brain barrier disruption when compared to white matter lesions 12,14,15 . In post mortem samples taken from individuals in the advanced stages of multiple sclerosis, high numbers of immune cells were only detected in Type I grey matter lesions ( Figure 1A): all other grey matter lesions were categorized as relatively "noninflammatory" [11][12][13] .…”