title: Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin.
abstract: Cobra neurotoxin (NT) has central analgesic effects, but it is difficult to pass through brain blood barrier (BBB). A novel method of red light induction is designed to help NT across BBB, which is based on photosensitizer activation by red light to generate reactive oxygen species (ROS) to open BBB. The effects were evaluated on cell models and animals in vivo with illumination by semiconductor laser at 670nm on photosensitizer pheophorbide isolated from silkworm excrement. Brain microvascular endothelial cells and astrocytes were co-cultured to build up BBB cell model. The radioactivity of (125)I-NT was measured in cells and tissues for NT permeation. Three ways of cranial irradiation, nasal cavity and intravascular irradiation were tested with combined injection of (125)I-NT 20μg/kg and pheophorbide 100μg/kg to rats, and organs of rats were separated and determined the radioactivity. Paw pressure test in rats, hot plate and writhing test in mice were applied to appraise the analgesic effects. NT across BBB cell model increased with time of illumination, and reached stable level after 60min. So did ROS in cells. NT mainly distributed in liver and kidney of rats, significantly increased in brain after illumination, and improved analgesic effects. Excitation of pheophorbide at red light produces ROS to open BBB, help NT enter brain, and enhance its central action. This research provides a new method for drug across BBB to improve its central role.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. Electronic address: yeyong@scut.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Fang
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001522:Behavior, Animal / Q000187:drug effects / Q000528:radiation effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000528:radiation effects; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry / Q000494:pharmacology*; D017815:Elapidae / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D007457:Iodine Radioisotopes / Q000737:chemistry; D008027:Light; D008297:Male; D051379:Mice; D008954:Models, Biological; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000700:Analgesics; D003039:Cobra Neurotoxin Proteins; D007457:Iodine Radioisotopes; D017382:Reactive Oxygen Species
keywords: Blood brain barrier; Central analgesic; Cobra neurotoxin; Permeation; Red light