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


METHODS
Wistar rats and C57/BL6 mice underwent occlusion of the middle cerebral artery (MCAO) for 2 hours. Forty minutes after filament introduction, animals breathed either 100% O2 at 3.0 atmospheres absolute (ata; HBO group) or at 1.0 ata (control) for 1 hour in an HBO chamber. In rats, MRI was performed 15 minutes after MCAO and after 15 minutes and 3, 6, 24, and 72 hours of reperfusion. In mice, BBB permeability for sodium fluorescein was measured after 24-hour reperfusion.


RESULTS
Increased BBB permeability on postcontrast T1-weighted (T1w) images had a biphasic pattern. HBO reduced volumes and intensity of enhancement. Mean abnormal enhancing volumes were 71+/-10 mm3 (control) versus 47+/-10 mm3 (HBO) at 15 minutes; 111+/-21 mm3 versus 69+/-17 mm3 3 hours; 147+/-44 mm3 versus 83+/-21 mm3 6 hours; 150+/-37 mm3 versus 89+/-14 mm3 24 hours; and 322+/-52 mm3 versus 215+/-21 mm3 72 hours (all P<0.05). Interhemispheric quotients of mean gray values on T1w were at 1.73+/-0.11 versus 1.57+/-0.07 15 minutes; 1.74+/-0.07 versus 1.60+/-0.06 at 3 hours; 1.77+/-0.07 versus 1.62+/-0.06 at 6 hours; 1.79+/-0.10 versus 1.60+/-0.05 at 24 hours; and 1.81+/-0.10 versus 1.62+/-0.07 at 72 hours (all P<0.05). HBO-treated mice had significantly lower postischemic BBB permeability than mice treated with either normobaric hyperoxia or room air. Vasogenic edema assessed on T2w images and histologic sections was significantly lower in HBO-treated rats.


CONCLUSIONS
Intraischemic HBO therapy reduces early and delayed postischemic BBB damage and edema after focal ischemia in rats and mice.
Veltkamp
Roland
R
Department of Neurology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. roland_veltkamp@med.uni-heidelberg.de
Siebing
Dirk A
DA
Sun
Li
L
Heiland
Sabine
S
Bieber
Katja
K
Marti
Hugo H
HH
Nagel
Simon
S
Schwab
Stefan
S
Schwaninger
Markus
M
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D002536:Cerebral Arteries / Q000601:surgery; D002561:Cerebrovascular Disorders / Q000473:pathology / Q000628:therapy; D004487:Edema / Q000473:pathology* / Q000628:therapy; D019793:Fluorescein / Q000494:pharmacology; D006931:Hyperbaric Oxygenation; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000628:therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000473:pathology; D023421:Models, Animal; D010100:Oxygen / Q000378:metabolism; D011312:Pressure; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D013223:Statistics as Topic; D013997:Time Factors
D010100:Oxygen; D019793:Fluorescein