title: Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension.
abstract: The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40-45 mmHg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.
authors.affiliation: Section of Clinical CNS Research, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Bendel
authors.forename: Kanar
authors.initials: K
authors.lastname: Alkass
authors.forename: Tjerk
authors.initials: T
authors.lastname: Bueters
authors.forename: Mia
authors.initials: M
authors.lastname: von Euler
authors.forename: Gabriel
authors.initials: G
authors.lastname: von Euler
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology*; D016893:Carotid Stenosis / Q000473:pathology*; D002452:Cell Count; D006221:Halothane / Q000633:toxicity*; D007022:Hypotension / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006221:Halothane