Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study

Abstract

The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.

Influence of white matter injury on gray matter reactive gliosis upon stab wound in the adult murine cerebral cortex

“…Thus, the dynamics of astrocyte proliferation are similar across regions, but the extent of their proliferation is initially lower in the WM. Indeed, access to vascular‐derived signals that are important for GM astrocyte proliferation (Bardehle et al, ; Sirko et al, ) might be less accessible for WM astrocytes given the lower vessel density in the WM in mice and human patients (Ballabh, Braun, & Nedergaard, ; Cavaglia et al, ; Joutel & Chabriat, ; Nyúl‐Tóth et al, ).…”

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

“…In this work, the results demonstrated that although TGs could significantly increase the expressions of ZO-1, claudin-5, and occludin proteins in MCAO-induced brain tissues, neither PSs nor OSs did. The BBB consists of cerebral endothelial cells and is closely associated with pericytes (Nyul-Toth et al, 2016). Pericytes are vital to BBB integrity (Bell et al, 2010).…”

Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy

“…Unfortunately, NGF is not able to pass the BBB which effectively controls the cellular and molecular traffic between the brain and the periphery [8,44]. To bypass this barrier, previous studies utilized infusion into cerebral ventricles leading to a significant…”