Journal
EXPERIMENTAL NEUROLOGY
Volume 237, Issue 1, Pages 18-25Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2012.06.007
Keywords
Artificial oxygen carrier; Focal brain ischemia; Normobaric hyperoxygenation; Rat; Tissue hypoxia
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Funding
- Novaliq GmbH (Heidelberg)
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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; [SFA(0.5) or SFA(1.0)]) 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: SFA(1.0), 57 +/- 34 mm(3); controls, 217 +/- 70 mm(3); 24 h after MCAO: SFA(1.0), 189 +/- 82 mm(3); controls, 317 +/- 60 mm(3)) and of P-Add immunoreactivity (8 h after MCAO: SFA(1.0), 261 +/- 37 mm(3); controls, 339 +/- 26 mm(3); 24 h after MCAO: SFA(1.0), 274 +/- 47 mm(3); controls, 364 +/- 46 mm(3)). 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. (c) 2012 Elsevier Inc. All rights reserved.
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