Delayed cerebrovascular protective effect of lipopolysaccharide in parallel to brain ischemic tolerance.
Cerebrovascular abnormalities, in endothelium and smooth muscle compartments, occur in the course of cerebral ischemia-reperfusion as evidenced by the impairment of endothelium-dependent relaxation and decrease in potassium inward rectifier density in occluded middle cerebral arteries (MCAs). The authors investigated whether a delayed vascular protection occurred in a model of brain ischemic tolerance. A low dose of lipopolysaccharide (0.3 mg/kg) administered 72 h before MCA occlusion induced a significant decrease in infarct volume. In parallel to this delayed neuroprotective effect, lipopolysaccharide prevented the ischemia-reperfusion-induced impairment of endothelium relaxation. In addition, lipopolysaccharide prevented the postischemic alteration of potassium inward rectifier-dependent smooth muscle relaxation as well as the decrease in potassium inward rectifier density measured by patch-clamp in dissociated vascular smooth muscle cells originated from the occluded MCA. These results suggest that during brain ischemic tolerance, lipopolysaccharide is able to induce both a delayed neuroprotective and vasculoprotective effect.
Bastide
Michèle
M
Equipe d'Accueil (EA 1046), Laboratoire de Pharmacologie, Faculté de Médecine et Centre Hospitalier et Universitaire de Lille, France.
Gelé
Patrick
P
Pétrault
Olivier
O
Pu
Qian
Q
Caliez
Audrey
A
Robin
Emmanuel
E
Deplanque
Dominique
D
Duriez
Patrick
P
Bordet
Régis
R
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020768:Middle Cerebral Artery / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D024661:Potassium Channels, Inwardly Rectifying