title: Retrograde perfusion of the cerebral vein with antioxidant LY231617 reduces brain damage in the rat focal ischemia model.
abstract: Retrograde perfusion of the cerebral vein (RPCV) with antioxidant LY231617 was evaluated in the focal ischemia model in rats as a new therapeutic route to deliver cytoprotective agents more selectively and efficiently into ischemic brain tissue. Thirty-six Sprague-Dawley rats were divided into Groups A through D. Focal ischemia was induced for 3 hours in the rats, then all groups were treated differently for 2 hours and then sacrificed. Rats in Group A (n = 10) served as the control group and was left untreated. Rats in Group B (n = 10) received an intravenous infusion of LY231617 (10 mg/kg/hr). Rats in Group C (n = 6) received saline (86 microliters/min) through RPCV. Rats in Group D (n = 10) received LY231617 (10 mg/kg/hr) in saline (86 microliters/min) through RPCV. The regional cerebral blood flow (rCBF) was measured using [14C]iodoantipyrine autoradiography, and phorbol 12,13-dibutyrate (PDBu) binding by in vitro [3H]PDBu autoradiography. Ischemic brain damage was assessed quantitatively after staining with cresyl violet and Luxol fast blue. Rats in Group D showed significantly higher rCBF (41-400%, p < 0.05) in the ischemic cortical and subcortical areas, and a significant reduction (66%, p < 0.01) in the total volume of ischemic damage and reduction of PDBu binding (p < 0.05) in the lateral striatum of the ischemic hemisphere, as compared to the rats in Groups A-C. RPCV with antioxidant LY231617 achieves a more beneficial effect on focal ischemic tissue than regular systemic administration.
authors.affiliation: Neuroisotope Laboratory, Montreal Neurological Institute, Quebec, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Nagao
authors.forename: Y L
authors.initials: YL
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002550:Cerebral Veins / Q000187:drug effects*; D007262:Infusions, Intravenous; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
chemical_list: D000975:Antioxidants; D002084:Butylated Hydroxytoluene; C081064:LY 231617