Hyperbaric oxygen-induced attenuation of hemorrhagic transformation after experimental focal transient cerebral ischemia.
OBJECTIVE
An increased risk of hemorrhagic transformation is a major factor limiting the use of tissue plasminogen activator for stroke. Increased hemorrhagic transformation is also found in animals undergoing transient focal cerebral ischemia with hyperglycemia; this study examined whether hyperbaric oxygen (HBO) could reduce such hemorrhagic transformation in a rat model.


METHODS
Rats received an injection of 50% glucose (6 mL/kg intraperitoneally) and had a middle cerebral artery occlusion 10 minutes later. Rats were treated with HBO (3 ATA for 1 hour) 30 minutes after middle cerebral artery occlusion. Control rats received normobaric room air. Rats underwent reperfusion 2 hours after middle cerebral artery occlusion. Blood-brain barrier permeability (Evans blue), hemorrhagic transformation (hemoglobin content), brain edema, infarct volume, and mortality were measured.


RESULTS
HBO treatment reduced Evans blue leakage in the ipsilateral hemisphere (28.4+/-3.5 versus 71.8+/-13.1 microg/g in control group, P<0.01) 2 hours after reperfusion and hemorrhagic transformation (0.13+/-0.13 versus 0.31+/-0.28 mg hemoglobin in the control group, P<0.05) 22 hours later. Mortality was less in the HBO group (4% versus 27% in controls, P<0.05). Mean infarct volume and swelling in the caudate were also less in HBO-treated rats (P<0.05), but HBO failed to reduce brain water content in the ipsilateral hemisphere (P>0.05).


CONCLUSIONS
Early intraischemic HBO treatment reduces the blood-brain barrier disruption, hemorrhagic transformation, and mortality after focal cerebral ischemia suggesting that HBO could be used to reduce hemorrhagic conversion in patients with stroke.
Qin
Zhiyong
Z
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Karabiyikoglu
Murat
M
Hua
Ya
Y
Silbergleit
Robert
R
He
Yangdong
Y
Keep
Richard F
RF
Xi
Guohua
G
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006931:Hyperbaric Oxygenation / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000009:adverse effects; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D006454:Hemoglobins; D010959:Tissue Plasminogen Activator; D010100:Oxygen