bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.01.29.702473

Urban PM2.5 at Realistic Environmental Concentrations Impairs Blood-Brain Barrier Integrity and Enhances LOX-1 Expression in Human Brain Endothelial Cells

Andersson, E.·Wendt, T.·Bergman, F.·Isaxon, C.·Ansar, S.
View original source ↗Export metadata ↓

Abstract

IntroductionAmbient air pollution, especially fine particulate matter 2.5 (PM2.5) has emerged as a critical environmental risk factor for cerebrovascular diseases, contributing to an estimated 7.9 million premature deaths annually. PM2.5 induces cellular toxicity and is hypothesized to disrupt the blood-brain barrier (BBB), a pathological hallmark in cerebrovascular diseases such as ischemic stroke. Despite epidemiological evidence linking PM2.5 to increased stroke incidence, its underlying cellular mechanism driving this association is poorly understood. It remains unclear how environmentally relevant pollution concentrations affects brain endothelial function or influence stroke-related biomarkers such as the lectin-like oxLDL receptor 1 (LOX-1). MethodPrimary adult male human brain microvascular endothelial cells (HBMEC) were exposed to PM2.5 (5, 15, 75, or 300 g/m3) collected from an urban environment in southern Sweden, or control. Thereafter, exposed to normoxia (21% O2) or hypoxia (1% O2) and glucose deprivation, followed by reperfusion as a model for ischemic stroke. Cell viability, oxidative stress, inflammation, BBB integrity (claudin-5, ZO-1) and LOX-1 protein expression were assessed. ResultsPM2.5 exposure induced cellular dysfunction, oxidative stress and inflammation starting at 75 g/m3 PM2.5. Notably, decreased claudin-5 and ZO-1 protein levels and increased LOX-1 expression at concentrations as low as 15 g/m3 PM2.5, levels commonly encountered in urban environments globally. The cellular effects of PM2.5 closely resembled those induced by ischemic-like injury. ConclusionThese findings demonstrate dose-dependent detrimental effects of PM2.5 on HBMEC. The results suggest that ambient urban PM2.5 may act as a predisposing factor for cerebrovascular disease onset, by causing endothelial and barrier dysregulation. HighlightsO_LIUrban PM2.5 dose-dependently disrupts BBB integrity in human brain endothelial cells C_LIO_LIPM2.5 induces endothelial dysfunction resembling ischemic-like injury C_LIO_LIUrban PM2.5 exposure upregulates cardiovascular disease biomarker LOX-1 C_LIO_LIA majority of the global population are exposed to BBB-disrupting PM2.5 levels C_LIO_LIVascular endothelial- and BBB dysfunction enhances risk for cerebrovascular disease C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/702473v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@42cce6org.highwire.dtl.DTLVardef@19a2ff9org.highwire.dtl.DTLVardef@1c38e7corg.highwire.dtl.DTLVardef@1bfa837_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Andersson, E., Wendt, T., Bergman, F., Isaxon, C., Ansar, S.. 2026-02-02. Urban PM2.5 at Realistic Environmental Concentrations Impairs Blood-Brain Barrier Integrity and Enhances LOX-1 Expression in Human Brain Endothelial Cells. https://doi.org/10.64898/2026.01.29.702473

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts

Accumulation of proteins such as amyloid beta (Abeta), hyperphosphorylated tau and alpha-synuclein within the brain alters neural information processing and causes neurodegeneration(1-3), but how toxic solutes are cleared from the brain remains highly controversial(4,5). Proposed exit routes include efflux across endothelial cells into the blood(6,7), and movement to the pial surface via vasomotion-induced pumping along spaces within arteriolar smooth muscle(8) or via outflow along the perivascular space of ascending venules promoted by water flux through astrocytes (the glymphatic system(9)). From the pial surface of the brain, drainage may continue to dural lymphatics, along the outer sheaths of exiting cranial nerves and across the cribriform plate(10-14). We now report the presence, in mice and humans, of 2 micron diameter conduits that remove fluorescently labelled tau and Abeta from the brain. These conduits form a spatially-organised mesh within the walls of penetrating arterioles and pial arteries, and around the surface of ascending venules and deep cerebral and pial veins. They course through the pial and arachnoid layers to span the CSF space, wrapping the brain and cranial nerves. They are formed of reticular fibroblasts, which label for VE-cadherin(15) and PDGFRalpha(16), the lymphatic markers(17) podoplanin, VEGFR3 and Prox1, and reticular fibroblast extracellular matrix components collagen I and VI(16,18-20). Parenchymal tau drains from the brain at a similar rate via arteriolar conduits and via conduits around venules, arguing against preferential removal by a glymphatic mechanism. In Alzheimer's disease model mice, Abeta is seen traversing these lymph node-like conduits. Modulation of molecular transfer via this route may accelerate or delay cognitive decline, and slowed transfer from arteriolar to pial-arachnoid conduits may initiate cerebral amyloid angiopathy.

neuroscience↗
bioRxiv2026

Analysis of the influence of gradual changes in matrix sentence similarity on neural envelope tracking

Neural tracking of speech is a well-established phenomenon in neuroscience. However, for speech signals with a fixed structure, significant correlations between speech envelopes and neurophysiological representations occur even for unheard sentences. We exploit a structured speech-in-noise matrix hearing test (Oldenburger Sentence Test, OLSA) to systematically quantify the relationship between acoustic sentence similarity and neural tracking. Simultaneous magnetoencephalography (MEG) and 76-channel electroencephalography (EEG) data, including 16 channels positioned directly around the ears (ear-EEG), were recorded from 21 young adults with normal hearing during the presentation of clean-speech audiobooks and OLSA sentences at six signal-to-noise ratios. A linear decoder trained on audiobooks reconstructed OLSA sentence envelopes. Reconstruction accuracies were compared using a linear mixed model across heard (matched) and unheard (mismatched) sentences of varying acoustic similarity. Significant reconstruction accuracies were achieved across MEG, EEG, and ear-EEG for both matched and mismatched sentences. For mismatched sentences, these accuracies gradually increased with their acoustic similarity to the heard speech data. The high similarity between sentences, which is especially prominent in matrix tests, can cause significant spurious tracking for mismatched stimuli. This effect can reach levels comparable to those of matched sentences and can be mistaken for true neural tracking. Robust neural tracking across modalities further supported the established viability of ear-EEG compared to whole-head systems.

neuroscience↗
bioRxiv2026

Seizures and tauopathy following neurotrauma are mediated by prion protein and metabotropic glutamate receptor 5

Traumatic brain injury (TBI) is one of the world's leading causes of death and disability and a major risk factor for dementias. The primary dementia associated with TBI is chronic traumatic encephalopathy (CTE), a neurodegenerative disease classified as a tauopathy, in which toxic tau molecules lead to disease pathologies and degeneration. The processes that lead to tauopathy and subsequent dementia after TBI remain unclear. Here, we built upon the finding that seizures after TBI may be a mechanism leading to tauopathy, by dissecting the functions of the metabotropic glutamate receptor 5 - cellular prion protein (mGluR5-PrPC) pathway. We delivered TBI to larval in a blast paradigm, and quantified aggregation of Tau via a genetically-encoded Tau-GFP fusion reporter. Zebrafish larvae lacking prp2 (homolog of mammalian cellular Prion Protein, PrPC) displayed a 168% increase in post-traumatic seizures activity after TBI. An mGluR5 agonist (CHPG) reduced post-traumatic seizures, whereas an mGluR5 antagonist (MPEP) increased post-traumatic seizures. Moreover, agonizing mGluR5 reduced tau aggregation and antagonizing mGluR5 increased tau burden. Larvae seizing from convulsants, rather than TBI, were treated with CHPG/MPEP and provided a similar pattern of outcomes, suggesting seizures may be a factor needed for mGluR5 activity to influence tau aggregation. The PrPC-mGluR5 pathway is proposed as one candidate pathomechanism linking TBI to subsequent seizures and tauopathy, and thus it warrants investigation as a target for prophylactic interventions.

neuroscience↗