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 (86μl/min) through RPCV. Rats in Group D (n=10) received LY231617 (10 mg/kg/hr) in saline (86μl/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.
