ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2010
Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 109 citations in OpenAlex.
- Ischemic stroke: molecular mechanisms of blood-brain barrier dysfunction and opportunities for drug development.Fluids and barriers of the CNS · 2026Review
- Inhibition of PKCγ phosphorylation protects against cerebral ischemia-reperfusion injury.Redox biology · 2026Article
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
- Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals.CNS neuroscience & therapeutics · 2025Review
- Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets.International journal of molecular sciences · 2024Article
- Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023Review
- The blood-brain barrier: structure, regulation, and drug delivery.Signal transduction and targeted therapy · 2023Review
- Article
- Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response.International journal of molecular sciences · 2022Article
- Blood-Brain Barrier Mechanisms in Stroke and Trauma.Handbook of experimental pharmacology · 2022Review
- Genomics as a Clinical Decision Support Tool for Identifying and Addressing Modifiable Causes of Cognitive Decline and Improving Outcomes: Proof of Concept Support for This Personalized Medicine Strategy.Frontiers in aging neuroscience · 2022Article
- Targeting Common Signaling Pathways for the Treatment of Stroke and Alzheimer's: a Comprehensive Review.Neurotoxicity research · 2021Review
- The impact of hypoxia on blood-brain, blood-CSF, and CSF-brain barriers.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Review
- The blood-brain and gut-vascular barriers: from the perspective of claudins.Tissue barriers · 2021Review
- Review
- The Molecular and Pathophysiological Functions of Members of the LNX/PDZRN E3 Ubiquitin Ligase Family.Molecules (Basel, Switzerland) · 2020Review
- Regulation of blood-brain barrier integrity by microglia in health and disease: A therapeutic opportunity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders.Frontiers in physiology · 2020Review
- The Blood-Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders.International journal of molecular sciences · 2019Review
- Claudin-5: gatekeeper of neurological function.Fluids and barriers of the CNS · 2019Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O(2)) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.
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Registered trials
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.