The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.

While the impact of hemorrhagic and ischemic strokes on the blood–brain barrier has been extensively studied, the impact of these types of stroke on the choroid plexus, site of the blood-CSF barrier, has received much less attention. The purpose of this review is to examine evidence of choroid plexus injury in clinical and preclinical studies of intraventricular hemorrhage, subarachnoid hemorrhage, intracerebral hemorrhage and ischemic stroke. It then discusses evidence that the choroid plexuses are important in the response to brain injury, with potential roles in limiting damage. The overall aim of the review is to highlight deficiencies in our knowledge on the impact of hemorrhagic and ischemic strokes on the choroid plexus, particularly with reference to intraventricular hemorrhage, and to suggest that a greater understanding of the response of the choroid plexus to stroke may open new avenues for brain protection.

Background Blood-brain barrier (BBB) pathology may be associated with mental disorders. The aim of this systematic review and meta-analysis is to identify, evaluate and summarize available evidence on whether potential biomarkers of BBB pathology are altered in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. Methods The primary outcome is blood S100B, while secondary outcomes include biomarkers in blood and/or cerebrospinal fluid, i.e. albumin ratio, fibrinogen, immunoglobulin G, glial fibrillary acidic protein, amyloid beta (Aβ), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases, endothelial glycocalyx constituents, and cell adhesion molecules (CAMs). A systematic search in PubMed, Embase and PsycINFO resulted in 131 eligible studies, of which 93 were included in the meta-analysis. Meta- and subgroup analyses were undertaken using random-effects modelling. The protocol was a priori registered on PROSPERO (CRD42020152721). Results S100B was increased in schizophrenia spectrum disorders (24 studies; 1107 patients; standardized mean difference (SMD) ​= ​0.82; 95% confidence interval (CI) ​= ​0.51 to 1.13; I 2 ​= ​90%), major depression (13 studies; 584 patients; SMD ​= ​0.57; 95% CI ​= ​0.31 to 0.83; I 2 ​= ​73%) and bipolar disorder (4 studies; 142 patients; SMD ​= ​0.55; 95% CI ​= ​0.16 to 0.94; I 2 ​= ​48%). Similarly, numerous secondary outcomes, including albumin ratio, fibrinogen, Aβ, MMPs and CAMs, were altered. Results of the included studies varied considerably, and important confounders were often not accounted for. Conclusions The findings implicate occurrence of BBB pathology in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. However, definite conclusions cannot be drawn, mainly because the investigated biomarkers are indirect measures of BBB pathology.

No abstract

Neurodegeneration is associated with inflammation and mismanaged iron homeostasis, leading to increased concentration of non‐transferrin‐bound iron (NTBI) in the brain. NTBI can be taken up by cells expressing Zrt‐, Irt‐like protein‐14 (ZIP14), which is regulated by iron overload and pro‐inflammatory cytokines, for example, interleukin‐1β (IL‐1β) and IL‐6. Here, we focus on the astrocytic involvement and regulation of ZIP14 in an experimental model of chronic neurodegeneration with inflammation and iron overload. Rats were unilaterally injected with ibotenic acid in striatum resulting in excitotoxicity‐induced neuronal loss in substantia nigra pars reticulata (SNpr). ZIP14 expression was measured in SNpr using immunohistochemistry, western blotting, and RT‐qPCR. Cultures of primary astrocytes were examined for Zip14 mRNA expression after stimulation with ferric ammonium citrate (FAC), IL‐6, or IL‐1β. To study the involvement of ZIP14 in astrocytic iron uptake, uptake of 59Fe was investigated after treatment with IL‐1β and siRNA‐mediated ZIP14 knockdown. In the lesioned SNpr, reactive astrocytes, but not microglia, revealed increased ZIP14 expression with a main confinement to cell bodies and cellular processes. In astrocyte cultures, FAC and IL‐1β stimulation increased Zip14 expression and IL‐1β stimulation increased uptake of 59Fe. Increased 59Fe uptake was also observed after siRNA‐mediated ZIP14 knockdown suggesting that lowering of ZIP14 impaired the balance between astrocytic uptake and export of iron. We conclude that astrocytes increase ZIP14 expression in response to inflammation and iron exposure and that ZIP14 seems pertinent for iron uptake in astrocytes and plays a role for a balanced astrocytic iron homeostasis.