title: Elimination kinetics of domoic acid from the brain and cerebrospinal fluid of the pregnant rat.
abstract: Domoic acid (DA) causes neurological effects in multiple species upon exposure, including status epilepticus in pregnant sea lions and an epileptic disease state that commonly develops in juveniles. This study aims to define brain toxicokinetic parameters in the pregnant rat in the larger context of maternal-fetal toxin transfer. Specifically, Sprague-Dawley rats were exposed to a low observable effect level of 1.0 mg DA/kg intravenously at gestational day 20, and plasma, brain, and cerebrospinal fluid (CSF) samples were taken at discrete time points over 24 h. Domoic acid concentrations were determined by a tandem LC/MS method recently optimized for brain tissue and CSF. Data showed that 6.6% of plasma DA reached the brain, 5.3% reached the CSF, and DA levels were nearly identical in both brain and CSF for 12 h, remaining above the threshold to activate isolated hippocampal neurons for 2 h. The calculated terminal half-life of CSF was 4 h, consistent with the time for complete CSF regeneration, suggesting that CSF acts as a mechanism to clear DA from the brain.
authors.affiliation: Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, NOAA, National Ocean Service, 219 Fort Johnson Road, Charleston, South Carolina 29412, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Maucher Fuquay
authors.forename: Noah
authors.initials: N
authors.lastname: Muha
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: John S
authors.initials: JS
authors.lastname: Ramsdell
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D008387:Marine Toxins / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D009498:Neurotoxins / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008387:Marine Toxins; D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid