Lipocortin-1 fails to ameliorate ischemic brain edema in the cat.
It has been reported that corticosteroids exert their anti-inflammatory action through de novo synthesis of phospholipase-inhibitory proteins called lipocortins (annexins). We postulated that the following may lessen the effectiveness of corticosteroids on acute ischemic brain edema: 1) lipocortins are induced several hours after administration of steroids; 2) de novo synthesis of lipocortins is suppressed in the ischemic brain; and 3) lipocortins induced systemically do not pass through the blood-brain barrier (BBB) to reach the sites of ischemic edema. To test this hypothesis, we examined whether dexamethasone, given long before ischemia or direct administration of recombinant lipocortin-1, combined with or without BBB opening, ameliorate ischemic brain edema. Three hours before occlusion of the middle cerebral artery (MCA) in the cat, 4 mg/kg of dexamethasone was injected intravenously. The animals were subjected to 4 hours of ischemia. Alternatively, 2 ug/ml (total volume 10 ml) of recombinant human lipocortin-1 (annexin-I) was perfused intermittently into the ischemic focus by catheterization into the MCA. Artificial opening of the BBB was performed by intra-arterial mannitol infusion. None of these strategies demonstrated amelioration of ischemic edema. We conclude that: Dexamethasone and recombinant lipocortin-1 seem unlikely to have robust effects on amelioration of acute ischemic edema.
Mima
T
T
Department of Neurosurgery, Kochi Medical School, Japan.
Shigeno
T
T
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000473:pathology*; D002415:Cats; D003907:Dexamethasone / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D011292:Premedication; D011994:Recombinant Proteins / Q000494:pharmacology
D017305:Annexin A1; D011994:Recombinant Proteins; D003907:Dexamethasone