ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Progranulin deficiency promotes post-ischemic blood-brain barrier disruption.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 95 citations in OpenAlex.
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unit.bioRxiv : the preprint server for biology · 2026Article
- Article
- Acute pancreatitis experimental models, advantages and disadvantages.Journal of physiology and biochemistry · 2025Review
- Lipid droplet accumulation in microglia and their potential roles.Lipids in health and disease · 2025Review
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Multiregional blood-brain barrier phenotyping identifies the prefrontal cortex as the most vulnerable region to ageing in mice.Brain communications · 2025Article
- Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons.Stem cells translational medicine · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.Cellular and molecular neurobiology · 2023Review
- Medial prefrontal cortex oxytocin mitigates epilepsy and cognitive impairments induced by traumatic brain injury through reducing neuroinflammation in mice.Scientific reports · 2023Article
- The protective effect of low-dose minocycline on brain microvascular ultrastructure in a rodent model of subarachnoid hemorrhage.Histochemistry and cell biology · 2023Article
- Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations.Brain : a journal of neurology · 2022Article
- Distinct cell type-specific protein signatures in GRN and MAPT genetic subtypes of frontotemporal dementia.Acta neuropathologica communications · 2022Article
- Involvement of Peripheral Monocytes with IL-1β in the Pathogenesis of West Syndrome.Journal of clinical medicine · 2022Article
- A narrative review of multiple mechanisms of progranulin in cancer: a potential target for anti-cancer therapy.Translational cancer research · 2021Review
- Lipid droplets in the nervous system.The Journal of cell biology · 2021Review
- Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy.International journal of molecular sciences · 2021Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations of progranulin (PGRN) have been linked to frontotemporal dementia, but little is known about the effects of PGRN deficiency on the brain in health and disease. PGRN has been implicated in neurovascular development, inflammation, and Wnt signaling, a pathway involved in the formation of the blood-brain barrier (BBB). Because BBB alterations and inflammation contribute to ischemic brain injury, we examined the role of PGRN in the brain damage produced by ischemia-reperfusion. PGRN(+/-) and PGRN(-/-) mice underwent middle cerebral artery occlusion (MCAO) with monitoring of cerebral blood flow. Infarct volume and motor deficits were assessed 72 h later. Post-ischemic inflammation was examined by expression of inflammatory genes and flow cytometry. BBB structure and permeability were examined by electron microscopy (EM) and Evans blue (EB) extravasation, respectively. MCAO resulted in ~60% larger infarcts in PGRN(+/-) and PGRN(-/-) mice, an effect independent of hemodynamic factors or post-ischemic inflammation. Rather, massive hemorrhages and post-ischemic BBB disruption were observed, unrelated to degradation of tight junction (TJ) proteins or matrix metalloproteinases (MMPs). By EM, TJ were 30-52% shorter, fewer, and less interlocking, suggesting a weaker seal between endothelial cells. Intracerebral injection of platelet-derived growth factor-CC (PDGF-CC), which increases BBB permeability, resulted in a more severe BBB breakdown in PGRN(+/-) and PGRN(-/-) than wild-type mice. We describe a previously unrecognized involvement of PGRN in the expression of key ultrastructural features of the BBB. Such a novel vasoprotective role of PGRN may contribute to brain dysfunction and damage in conditions associated with reduced PGRN function.
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