Retrograde perfusion of the cerebral vein with antioxidant LY231617 reduces brain damage in the rat focal ischemia model.

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.