Oxygen therapy in permanent brain ischemia: Potential and limitations

Background: Both normobaric (NBO) and hyperbaric (HBO) oxygen therapy are protective in transient cerebral ischemia. In contrast, in permanent ischemia models, which reflect the majority of clinical strokes, the effectiveness of NBO is unknown, and the effectiveness of HBO is controversial. The goals of the present study were to compare both oxygen therapies in 2 models of permanent ischemia, to study the effect of time window, and to evaluate the combination of both oxygen therapies. Methods: Distal or proximal permanent occlusion of middle cerebral artery (MCAO) was induced by coagulation or filament, respectively. Mice received air, NBO, a single or repeated HBO (3 ata) treatments. Infarct sizes were quantified at 7 days (coagulation) and 24 h (filament), respectively. Results: Following MCA coagulation, infarct volume was 12.9 +/- 1.6 mm(3) in mice breathing air. When started 45 min or 120 min after MCAO, NBO (10.8 +/- 2.2) and significantly more potently HBO (7.8 +/- 0.9) reduced infarct size. Repeated HBO treatments had no additional effect (8.3 +/- 2.3). HBO also significantly decreased TUNEL cell staining at 24 h. Combination of 60 min NBO plus 60 min HBO resulted in smaller cortical infarcts (8.7 +/- 1.5) than 120 min NBO alone (11.1 +/- 3.2). In contrast, infarct volumes in filament-induced permanent MCAO did not differ among rodents receiving air (50 +/- 24 mm(3)), NBO (48 +/- 16), or HBO (46 +/- 21). After filament-induced transient MCAO, however, HBO reduced infarct volume significantly. Conclusions: NBO and more effectively HBO protect the brain against permanent cortical ischemia. In extensive focal ischemia, however, oxygen therapy is only effective in case of early recanalization. (c) 2006 Elsevier B.V. All rights reserved.