Abstract
We examined the temporal profiles of changes in the expressions of tight junction proteins (TJPs; namely, claudin-5, occludin, and ZO-1) after focal cerebral ischemia/reperfusion in mice. We also examined the effects of delayed treatment with tissue plasminogen activator (tPA) on the expressions of TJPs and angiopoietin (Ang) -1/2/Tie2. Mice subjected to a 6-h filamental middle cerebral artery (MCA) occlusion were treated with tPA (10 mg/kg, intravenously, just after the start of reperfusion) or vehicle. The expressions of TJPs were significantly decreased in the early phase of ischemia/reperfusion, and then gradually recovered. A delayed treatment with tPA decreased the expressions of TJPs when examined at 42 h after reperfusion. In contrast, delayed tPA treatment markedly increased Ang-2, but not Ang-1 expression, when examined at 30 h after reperfusion. Treatment with tPA at 300 g/ml also significantly decreased Ang- 2, but not Tie2 expression, in an in vitro monolayer model generated using human brain microvascular endothelial cells subjected to serum-deprivation. These findings suggest that delayed tPA treatment prevents recovery of TJPs following focal cerebral ischemia/reperfusion, partially via upregulation of Ang-2.
Keywords: Angiopoietin, Blood-brain barrier, Stroke, Tie2, Tight junction proteins, Tissue plasminogen activator
Current Neurovascular Research
Title:Tissue Plasminogen Activator Prevents Restoration of Tight Junction Proteins Through Upregulation of Angiopoietin-2
Volume: 10 Issue: 1
Author(s): Keisuke Mishiro, Mitsunori Ishiguro, Yukiya Suzuki, Kazuhiro Tsuruma, Masamitsu Shimazawa and Hideaki Hara
Affiliation:
Keywords: Angiopoietin, Blood-brain barrier, Stroke, Tie2, Tight junction proteins, Tissue plasminogen activator
Abstract: We examined the temporal profiles of changes in the expressions of tight junction proteins (TJPs; namely, claudin-5, occludin, and ZO-1) after focal cerebral ischemia/reperfusion in mice. We also examined the effects of delayed treatment with tissue plasminogen activator (tPA) on the expressions of TJPs and angiopoietin (Ang) -1/2/Tie2. Mice subjected to a 6-h filamental middle cerebral artery (MCA) occlusion were treated with tPA (10 mg/kg, intravenously, just after the start of reperfusion) or vehicle. The expressions of TJPs were significantly decreased in the early phase of ischemia/reperfusion, and then gradually recovered. A delayed treatment with tPA decreased the expressions of TJPs when examined at 42 h after reperfusion. In contrast, delayed tPA treatment markedly increased Ang-2, but not Ang-1 expression, when examined at 30 h after reperfusion. Treatment with tPA at 300 g/ml also significantly decreased Ang- 2, but not Tie2 expression, in an in vitro monolayer model generated using human brain microvascular endothelial cells subjected to serum-deprivation. These findings suggest that delayed tPA treatment prevents recovery of TJPs following focal cerebral ischemia/reperfusion, partially via upregulation of Ang-2.
Export Options
About this article
Cite this article as:
Mishiro Keisuke, Ishiguro Mitsunori, Suzuki Yukiya, Tsuruma Kazuhiro, Shimazawa Masamitsu and Hara Hideaki, Tissue Plasminogen Activator Prevents Restoration of Tight Junction Proteins Through Upregulation of Angiopoietin-2, Current Neurovascular Research 2013; 10 (1) . https://dx.doi.org/10.2174/1567202611310010006
DOI https://dx.doi.org/10.2174/1567202611310010006 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Hypertension in Hemodialysis Patients
Current Hypertension Reviews Evaluation of Vancoplus Versus Ceftriaxone Against Cephalosporin Resistance MRSA Strain in Experimental Meningitis Model
Cardiovascular & Hematological Disorders-Drug Targets Toxicogenomics to Evaluate Endocrine Disrupting Effects of Environmental Chemicals Using the Zebrafish Model
Current Genomics Serum Endocan, Neuron-Specific Enolase and Ischemia-Modified Albumin Levels in Newborns with Partial Blood Exchange Transfusion
Combinatorial Chemistry & High Throughput Screening Cerebral Vascular Aging: Extending the Concept of Pulse Wave Encephalopathy Through Capillaries to the Cerebral Veins
Current Aging Science Pharmacological Interactions on Blood Pressure Control in Arterial Hypertension, An Issue not to be Overlooked
Cardiovascular & Hematological Disorders-Drug Targets The Decisive Role of Mutual Arrangement of Hydroxy and Methoxy Groups in (3(4)-hydroxy-4(3)-methoxyphenyl)-4,7-dimethyl-3,4,4a,5,8,8ahexahydro- 2H-chromene-4,8-diols in their Biological Activity
Letters in Drug Design & Discovery Current and Potential Anticancer Drugs Targeting Members of the UHRF1 Complex Including Epigenetic Modifiers
Recent Patents on Anti-Cancer Drug Discovery Atheroprotective Properties of Pigment Epithelium-Derived Factor (PEDF) in Cardiometabolic Disorders
Current Pharmaceutical Design Co-Treatment with Anthocyanins and Vitamin C Ameliorates Ethanol- Induced Neurodegeneration via Modulation of GABAB Receptor Signaling in the Adult Rat Brain
CNS & Neurological Disorders - Drug Targets Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model
Current Alzheimer Research Emerging Drugs and Indications for Cardio-Metabolic Disorders in People with Severe Mental Illness
Current Pharmaceutical Design The Double Roles of the Prostaglandin E<sub>2</sub> EP2 Receptor in Intracerebral Hemorrhage
Current Drug Targets Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents
Recent Patents on Inflammation & Allergy Drug Discovery Matrix Metalloproteinase Inhibitors as Prospective Agents for the Prevention and Treatment of Cardiovascular and Neoplastic Diseases
Current Topics in Medicinal Chemistry Methamphetamine and HIV Infection, Role in Neurocognitive Dysfunction
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Living Life to the Fullest: Early Integration of Palliative Care into the Lives of Children with Chronic Complex Conditions
Current Pediatric Reviews Use of Telemetry Blood Pressure Transmitters to Measure Intracranial Pressure (ICP) in Freely Moving Rats
Current Neurovascular Research Anti PD-1 and PDL-1 Immunotherapy in the Treatment of Advanced Non- Small Cell Lung Cancer (NSCLC): A Review on Toxicity Profile and its Management
Current Drug Safety Centralized and Local Color Doppler Ultrasound Reading Agreement for Diagnosis of the Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis
Current Neurovascular Research