Hyperbaric oxygen reduces blood-brain barrier damage and edema after transient focal cerebral ischemia

Hyperbaric oxygen (HBO) has been shown to protect the brain parenchyma against transient focal cerebral ischemia but its effects on the ischemic microcirculation are largely unknown. We examined the potential of HBO to reduce postischemic blood-brain barrier (BBB) damage using repetitive MR-imaging and Na-Fluorescein uptake during 72 h of reperfusion and measured the effect of HBO on postischemic edema. Wistar rats and C57/Bl6 mice underwent focal ischemia for 2 h induced by filament occlusion of the middle cerebral artery (MCAO). Forty minutes after filament introduction, animals were placed in a HBO chamber and breathed either 100% O2 at 3.0 atmospheres absolute (ata; HBO group) or at 1.0 ata (control) for 1 h. In rats, MR-images were obtained 15 min after MCAO, and after 15 min, 3, 6, 24, 72 h of reperfusion. Volume of T1w postcontrast enhancement and an interhemispheric quotient of mean gray values (MGV) in T1w images were calculated for estimation of BBB damage. In ischemic mice, BBB permeability for Na-Fluorescein was measured fluoroscopically after 24 h of reperfusion. Physiological parameters and ischemic MR-perfusion did not differ between groups. Increased postischemic BBB permeability on postcontrast T1w images had a biphasic pattern and was located within the hyperintense areas on DWI and T2w images, respectively. HBO reduced volume of early and delayed BBB damage on postcontrast T1w images. Mean abnormal enhancing volumes at the various time points were at 15 min of reperfusion: 29±7 mm³ (control) vs. 19±6 mm³ (HBO); at 3 h: 38±11 mm³ vs. 28±7 mm³; at 6 h: 49±16 mm³ vs. 31±8 mm³; at 24 h: 51±14 mm³ vs. 35±8 mm³; at 72 h: 97±28 mm³ vs. 68±17 mm³ (p<0.05 for 6, 24, 72 h). The quotient of MGV was significantly lower in the HBO treated animals at all time points: at 15 min of reperfusion: 1.73±0.11 (control) vs. 1.57±0.07 (HBO); at 3 h: 1.74±0.07 vs. 1.60±0.06; at 6 h: 1.77±0.07 vs. 1.62±0.06; at 24 h: 1.79±0.10 vs. 1.60±0.05; at 72 h: 1.81±0.10 vs. 1.62±0.07. Reduction of postischemic BBB damage by HBO was confirmed in mice. After 24 h of reperfusion, mean interhemispheric quotient (ischemic/nonischemic) of relative fluorescence units was significantly larger in control (1.56±0.50) than in HBO (1.11±0.16) treated mice. Effect of HBO on ischemic focal brain edema was estimated by two ways. First, volume of hyperintensity on T2w images, which represent both parenchymal damage and brain edema in the ischemic hemisphere, was significantly larger in control than in HBO treated animals at 72 h after MCAO. Second, on histological sections, volume attributable to focal edema was 72±29 mm³ in the control and 41±14 mm³ in the HBO group (p<0,05). In conclusion, early administration of HBO reduces rapid and delayed BBB damage and brain edema after transient focal cerebral ischemia. The molecular and cellular targets of this HBO effect and its potential implications for reduction of secondary microvascular complications are currently under investigation.