Hyperbaric oxygen-induced attenuation of hemorrhagic transformation after experimental focal transient cerebral ischemia

Background and Purpose - 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 mu g/ 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.