ArticleFluids and barriers of the CNS2024
Endothelial and mural laminin-α5 contributes to neurovascular integrity maintenance.
Article in Fluids and barriers of the CNS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 11 citations in OpenAlex.
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- Loss of Pericytic Integrin-β1 Exacerbates Blood-Brain Barrier Damage and Hemorrhagic Brain Injury.Stroke · 2026Article
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- The regulatory network of Mfsd2a in cerebral ischemia: a novel time-targeted intervention framework.Molecular biology reports · 2026Review
- Oligodendrocyte integrin-β1 regulates blood-brain barrier and remyelination in hemorrhagic brain.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Roles and therapeutic prospects of the laminin family in disorders of the nervous system.Journal of translational medicine · 2026Review
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- Functions of the basal lamina and ApoE in cerebral amyloid angiopathy.Fluids and barriers of the CNS · 2025Review
- Microvascularization of the Vocal Folds: Molecular Architecture, Functional Insights, and Personalized Research Perspectives.Journal of personalized medicine · 2025Review
- Retinoic acid-inducible gene-I aggravates neuroinflammation in early brain injury after subarachnoid hemorrhage through mediating brain microvascular endothelial cell pyroptosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Recent advances in nanomaterial-based brain-targeted delivery systems for glioblastoma therapy.Nanomedicine (London, England) · 2025Review
- Extracellular matrix: unlocking new avenues in cancer treatment.Biomarker research · 2025Review
- Laminins and the blood-brain barrier.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- A dispensable role of mural cell-derived laminin-Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Tracking pericyte dysfunction in Alzheimer's disease: The emerging role of cerebrospinal fluid platelet-derived growth factor receptor-β.Tzu chi medical journalReview
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8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLaminin-α5, a major component of the basal lamina, is predominantly synthesized by endothelial and mural cells (pericytes and vascular smooth muscle cells) in the CNS. Loss of laminin-α5 in either population fails to induce any abnormalities due to functional redundancy. Thus, the functional significance of laminin-α5 in neurovascular integrity remains unknown. Here, we hypothesize that ablation of laminin-α5 in both endothelial and mural cells increases neurovascular permeability.
methodsThe compound knockout mice were generated by crossing laminin-α5 floxed mice with Tie2-Cre and PDGFRβ-Cre, which target endothelial cells and mural cells, respectively. Neurovascular permeability in these mutants was determined with both exogenous and endogenous tracers. Endothelial paracellular and transcellular permeability was assessed by examining the expression of tight junction proteins and transcytosis-associated proteins. In addition, transmission electron microscopy (TEM) was used to visualize tight junction ultrastructure and endothelial caveolae vesicles. Defects in pericytes and astrocytes were investigated by examining pericyte coverage/contact and astrocyte polarity.
resultsElevated neurovascular permeability was observed in the mutants. Subsequent studies found increased Caveolin-1 and decreased major facilitator superfamily domain-containing protein 2a (MFSD2A) expression, but unaltered Claudin-5 or zonula occludens-1 (ZO-1) expression. Consistent with these results, mutant mice exhibited increased endothelial caveolae vesicle number with intact tight junction structure under TEM. Additionally, pericyte coverage and contact were also decreased in the mutant mice, while astrocyte polarity was unaffected.
conclusionsThese results strongly indicate that endothelial and mural cell-derived laminin-α5 actively maintains neurovascular integrity via the transcellular rather than paracellular mechanism.
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