title: Effects of interleukin-1ß on cortical spreading depolarization and cerebral vasculature.
abstract: During brain damage and ischemia, the cytokine interleukin-1ß is rapidly upregulated due to activation of inflammasomes. We studied whether interleukin-1ß influences cortical spreading depolarization, and whether lipopolysaccharide, often used for microglial stimulation, influences cortical spreading depolarizations. In anaesthetized rats, cortical spreading depolarizations were elicited by microinjection of KCl. Interleukin-1ß, the IL-1 receptor 1 antagonist, the GABAAreceptor blocker bicuculline, and lipopolysaccharide were administered either alone or combined (interleukin-1ß + IL-1 receptor 1 antagonist; interleukin-1ß + bicuculline; lipopolysaccharide + IL-1 receptor 1 antagonist) into a local cortical treatment area. Using microelectrodes, cortical spreading depolarizations were recorded in a non-treatment and in the treatment area. Plasma extravasation in cortical grey matter was assessed with Evans blue. Local application of interleukin-1ß reduced cortical spreading depolarization amplitudes in the treatment area, but not at a high dose. This reduction was prevented by IL-1 receptor 1 antagonist and by bicuculline. However, interleukin-1ß induced pronounced plasma extravasation independently on cortical spreading depolarizations. Application of lipopolysaccharide reduced cortical spreading depolarization amplitudes but prolonged their duration; EEG activity was still present. These effects were also blocked by IL-1 receptor 1 antagonist. Interleukin-1ß evokes changes of neuronal activity and of vascular functions. Thus, although the reduction of cortical spreading depolarization amplitudes at lower doses of interleukin-1ß may reduce deleterious effects of cortical spreading depolarizations, the sum of interleukin-1ß effects on excitability and on the vasculature rather promote brain damaging mechanisms.
authors.affiliation: 1 Institute of Physiology I/Neurophysiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Richter
authors.affiliation: 1 Institute of Physiology I/Neurophysiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Eitner
authors.affiliation: 1 Institute of Physiology I/Neurophysiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Leuchtweis
authors.affiliation: 2 Institute of Molecular Cell Biology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.affiliation: 3 Pain Institute and Center for Medical Education, Düsseldorf, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Lehmenkühler
authors.affiliation: 1 Institute of Physiology I/Neurophysiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000069280:Electrocorticography; D004569:Electroencephalography; D058847:Inflammasomes / Q000187:drug effects; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D011189:Potassium Chloride; D001640:Bicuculline
keywords: Electrophysiology; blood–brain-barrier; neuronal–glial interaction; receptors; spreading depression