Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

Abstract

Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane (SFA)-containing emulsion together with normobaric hyperoxygenation (NBO). The spread of tissue hypoxia was studied using pimonidazole given prior to filament-induced middle cerebral artery occlusion (MCAO, 2h). Treatment consisted of intravenous injection of saline or the SFA-containing emulsion (0.5 or 1.0ml/100g body weight; [SFA0.5 or SFA1.0]) either upon establishing MCAO (early treatment) or after filament removal (delayed treatment). After injection NBO was administered for 8h (early treatment) or 6h (delayed treatment). Experiments were terminated 8 or 24h after MCAO. In serial brain sections tissue hypoxia and irreversible cell damage were quantitatively determined. Furthermore, we studied hypoxia-related gene expression (VEGF, flt-1). Early treatment significantly (p<0.05) reduced the volumes of tissue damage (8h after MCAO: SFA1.0, 57±34mm³; controls, 217±70mm³; 24h after MCAO: SFA1.0, 189±82mm³; controls, 317±60mm³) and of P-Add immunoreactivity (8h after MCAO: SFA1.0, 261±37mm³; controls, 339±26mm³; 24h after MCAO: SFA1.0, 274±47mm³; controls, 364±46mm³). Delayed treatment was comparably successful. The volume of the hypoxic penumbra was not decreased by the treatment. Similarly, VEGF and flt-1 mRNA levels did not differ between the experimental groups. From these data we conclude that increasing the blood oxygen transport capacity in the plasma compartment provides a neuroprotective effect by alleviating the severity of hypoxia to a level sufficient to prevent cells from transition into irreversible damage.