ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 114 citations in OpenAlex.
- MINocyclinE to Reduce inflammation and blood-brain barrier leakage in small Vessel diseAse (MINERVA): A phase II, randomized, double-blind, placebo-controlled experimental medicine trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Trial
- Vascular dementia and vascular cognitive impairment-current treatments and future prospects.International journal of stroke : official journal of the International Stroke Society · 2026Review
- Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury.Nature communications · 2026Article
- Roles of Microglia in Cerebral Small Vessel Disease.CNS neuroscience & therapeutics · 2026Review
- Mechanisms of Tianma Gouteng Yin in Treating Hypertension-Associated Vascular Cognitive Impairment: Insights from Experiments, Network Pharmacology, and Molecular Docking.Chinese journal of integrative medicine · 2026Article
- MCC950 suppresses NLRP3-dependent neuroinflammation and ameliorates cognitive decline in a rat model of cerebral small vessel disease.Neural regeneration research · 2026Article
- Microglial reactivity predicts hippocampal, but not global, atrophy in cerebral small vessel disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The Molecular Neurobiology of NG2-Expressing Glial Cells in Cerebral Small Vessel Disease Pathogenesis.Molecular neurobiology · 2026Review
- Identification of distinct and shared biomarker panels in different manifestations of cerebral small-vessel disease through proteomic profiling.Nature aging · 2026Article
- The interplay between neuroinflammation and endothelial dysfunction in cerebral small vessel disease.Frontiers in immunology · 2026Review
- Hypertension promotes neuroinflammation, brain injury and cognitive impairment.Brain, behavior, & immunity - health · 2025Article
- Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.medRxiv : the preprint server for health sciences · 2025Article
- The Bidirectional Role of Hypoxia-Inducible Factor 1 Alpha in Vascular Dementia Caused by Chronic Cerebral Hypoperfusion.Molecular neurobiology · 2025Review
- Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Carotid endarterectomy and blood-brain barrier permeability in subjects with bilateral carotid artery stenosis.Chinese neurosurgical journal · 2025Article
- Cerebral blood flow is associated with plasma and PET biomarkers of tau pathology in middle age.Brain communications · 2025Article
- Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.International journal of stroke : official journal of the International Stroke Society · 2024Review
- Activation of NLRP3 inflammasome in a rat model of cerebral small vessel disease.Experimental brain research · 2024Article
- Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hypertensive small vessel disease is a major cause of vascular cognitive impairment (VCI). Spontaneously hypertensive/stroke prone rats (SHR/SP) with unilateral carotid artery occlusion (UCAO) and a Japanese permissive diet (JPD) have white-matter (WM) damage similar to that seen in VCI. We hypothesized that WM injury was due to hypoxia-mediated, blood-brain barrier (BBB) disruption. Twelve-week-old SHR/SP had UCAO/JPD and were studied with immunohistochemistry, biochemistry, multimodal magnetic resonance imaging (MRI), and Morris water maze (MWM) testing. One week after UCAO/JPD, WM showed a significant increase in hypoxia inducible factor-1α (HIF-1α), which increased further by 3 weeks. Prolyl hydroxylase-2 (PHD2) expression decreased at 1 and 3 weeks. Infiltrating T cells and neutrophils appeared around endothelial cells from 1 to 3 weeks after UCAO/JPD, and matrix metalloproteinase-9 (MMP-9) colocalized with inflammatory cells. At 3 weeks, WM immunostained for IgG, indicating BBB leakage. Minocycline (50 mg/kg intraperitoneally) was given every other day from weeks 12 to 20. Multimodal MRI showed that treatment with minocycline significantly reduced lesion size and improved cerebral blood flow. Minocycline improved performance in the MWM and prolonged survival. We propose that BBB disruption occurred secondary to hypoxia, which induced an MMP-9-mediated infiltration of leukocytes. Minocycline significantly reduced WM damage, improved behavior, and prolonged life.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.