Rapid and Reversible Enhancement of Blood–Brain Barrier Permeability Using Lysophosphatidic Acid
| Autor: | Ngoc H. On, Myron Toews, Sanjot Savant, Donald W. Miller |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Drug delivery to the brain
Biology Blood–brain barrier Permeability Mice chemistry.chemical_compound Molecular-weight size marker Lysophosphatidic acid medicine Animals Humans RNA Messenger Receptors Lysophosphatidic Acid Receptor Microvessel Cells Cultured Mice Inbred BALB C Optical Imaging Brain Transporter Magnetic Resonance Imaging medicine.anatomical_structure Neurology chemistry Biochemistry Blood-Brain Barrier Permeability (electromagnetism) Biophysics Cattle Female Original Article lipids (amino acids peptides and proteins) Neurology (clinical) Lysophospholipids biological phenomena cell phenomena and immunity Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 33:1944-1954 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/jcbfm.2013.154 |
| Popis: | The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain. |
| Databáze: | OpenAIRE |
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