کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3055635 | 1186522 | 2012 | 8 صفحه PDF | دانلود رایگان |
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, 2 h). Treatment consisted of intravenous injection of saline or the SFA-containing emulsion (0.5 or 1.0 ml/100 g 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 8 h (early treatment) or 6 h (delayed treatment). Experiments were terminated 8 or 24 h 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 (8 h after MCAO: SFA1.0, 57 ± 34 mm³; controls, 217 ± 70 mm³; 24 h after MCAO: SFA1.0, 189 ± 82 mm³; controls, 317 ± 60 mm³) and of P-Add immunoreactivity (8 h after MCAO: SFA1.0, 261 ± 37 mm³; controls, 339 ± 26 mm³; 24 h after MCAO: SFA1.0, 274 ± 47 mm³; controls, 364 ± 46 mm³). 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.
► Tissue hypoxia may play an important pathophysiological role in ischemic cell death.
► Increasing plasma oxygen content to improve oxygen supply is neuroprotective.
► Improving oxygen supply decreases the volume and severity of tissue hypoxia in focal ischemia.
► Artificial oxygen carriers may increase the therapeutic window in stroke.
Journal: Experimental Neurology - Volume 237, Issue 1, September 2012, Pages 18–25