BACKGROUND AND PURPOSE: Perihematomal edema exacerbates the mass effect of hematoma and contributes to early neurological deterioration after intracerebral hemorrhage (ICH). Oxygen therapy has protective effects on the blood-brain barrier (BBB). We aimed to examine the effects of oxygen therapy on edema formation and BBB permeability after ICH. METHODS: ICH was induced in mice by injecting autologous blood (30 µL) or collagenase (0.03 U) intrastriatally. Development of posthemorrhagic edema formation and BBB disruption was characterized by wet-dry-weight assays and sodium- fluorescein fluorospectrometry 1d, 3d, and 7d after ICH induction. In subsequent experiments, mice received air, normobaric (NBO), or hyperbaric oxygen (HBO; 3ata) for 60 min starting either 30, 60, or 120 min after ICH induction. Expression of occludin, claudin-5, zonula occludens-1, matrix metalloproteinases (MMPs), and hypoxia-inducible factor-1α (HIF-1α) was measured by Western blot and zymography. RESULTS: Posthemorrhagic edema formation (water content: blood-injection model 80.6 ± 0.3 %; collagenase injection model 83.3 ± 0.7 %) and BBB disruption (interhemispheric ratio of extravasated sodium fluorescein: blood-injection model 1.75 ± 0.07; collagenase injection model 3.02 ± 0.15) peaked 3d after ICH. NBO and HBO initiated within 30 min of ICH induction attenuated edema formation and BBB disruption (interhemispheric ratio of fluorescein; blood-injection air 1.75 ± 0.12, NBO 1.52 ± 0.08, HBO 1.49 ± 0.09; collagenase: air 3.04 ± 0.23, NBO 2.25 ± 0.21, HBO 2.17 ± 0.23) 3d after ICH, whereas delayed oxygen therapy had no effect. Early oxygen therapies prevented occludin degradation, MMP-9 activation, and reduced HIF-1α expression. CONCLUSION: Very early oxygen therapy can attenuate edema formation and BBB disruption after ICH, but the brief therapeutic time window suggests that the translational potential is limited.
BACKGROUND AND PURPOSE:Perihematomal edema exacerbates the mass effect of hematoma and contributes to early neurological deterioration after intracerebral hemorrhage (ICH). Oxygen therapy has protective effects on the blood-brain barrier (BBB). We aimed to examine the effects of oxygen therapy on edema formation and BBB permeability after ICH. METHODS:ICH was induced in mice by injecting autologous blood (30 µL) or collagenase (0.03 U) intrastriatally. Development of posthemorrhagic edema formation and BBB disruption was characterized by wet-dry-weight assays and sodium- fluorescein fluorospectrometry 1d, 3d, and 7d after ICH induction. In subsequent experiments, mice received air, normobaric (NBO), or hyperbaric oxygen (HBO; 3ata) for 60 min starting either 30, 60, or 120 min after ICH induction. Expression of occludin, claudin-5, zonula occludens-1, matrix metalloproteinases (MMPs), and hypoxia-inducible factor-1α (HIF-1α) was measured by Western blot and zymography. RESULTS:Posthemorrhagic edema formation (water content: blood-injection model 80.6 ± 0.3 %; collagenase injection model 83.3 ± 0.7 %) and BBB disruption (interhemispheric ratio of extravasated sodium fluorescein: blood-injection model 1.75 ± 0.07; collagenase injection model 3.02 ± 0.15) peaked 3d after ICH. NBO and HBO initiated within 30 min of ICH induction attenuated edema formation and BBB disruption (interhemispheric ratio of fluorescein; blood-injection air 1.75 ± 0.12, NBO 1.52 ± 0.08, HBO 1.49 ± 0.09; collagenase: air 3.04 ± 0.23, NBO 2.25 ± 0.21, HBO 2.17 ± 0.23) 3d after ICH, whereas delayed oxygen therapy had no effect. Early oxygen therapies prevented occludin degradation, MMP-9 activation, and reduced HIF-1α expression. CONCLUSION: Very early oxygen therapy can attenuate edema formation and BBB disruption after ICH, but the brief therapeutic time window suggests that the translational potential is limited.
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