Oxygen Therapy Reduces Secondary Hemorrhage after Thrombolysis in Thromboembolic Cerebral Ischemia

Abstract

Hyperbaric oxygen (HBO) and normobaric hyperoxia (NBO) protect the brain parenchyma and the cerebral microcirculation against ischemia. We studied their effect on secondary hemorrhage after thrombolysis in two thromboembolic middle cerebral artery occlusion (MCAO) (tMCAO) models. Beginning 60 minutes after tMCAO with either thrombin-induced thromboemboli (TT) or calcium-induced thromboemboli (CT), spontaneously hypertensive rats (n = 96) breathed either air, 100% O 2 (NBO), or 100% O 2 at 3 bar (HBO) for 1 hour. Immediately thereafter, recombinant tissue plasminogen activator (rt-PA, 9 mg/kg) was injected. Although significant reperfusion was observed after thrombolysis in TT-tMCAO, vascular occlusion persisted in CT-tMCAO. In TT-tMCAO, NBO and HBO significantly reduced diffusion-weighted imaging-magnetic resonance imaging (MRI) lesion volume and postischemic blood-brain barrier (BBB) permeability on postcontrast T1-weighted images. NBO and, significantly more potently, HBO reduced macroscopic hemorrhage on T2* MRI and on corresponding postmortem cryosections. Oxygen therapy lowered hemoglobin content and attenuated activation of matrix metalloproteinases in the ischemic hemisphere. In contrast, NBO and HBO failed to reduce infarct size in CT but both decreased BBB damage and microscopic hemorrhagic transformation. Only HBO reduced hemoglobin extravasation in the ischemic hemisphere. In conclusion, NBO and HBO decrease infarct size after thromboembolic ischemia only if recanalization is successful. As NBO and HBO also reduce postthrombolytic intracerebral hemorrhage, combining the two with thrombolysis seems promising.

Effect of Normobaric Oxygen Therapy in a Rat Model of Intracerebral Hemorrhage

“…16 However, future studies should carefully assess whether longer exposures to NBO may influence the pathophysiology of excitotoxicity, oxidative stress, inflammation, and cell death after hemorrhage. A final caveat involves the nature of our animal model.…”

Rapid Reversal of Anticoagulation Prevents Excessive Secondary Hemorrhage After Thrombolysis in a Thromboembolic Model in Rats

“…Hemorrhage on T2* MRI was classified into 5 categories as previously described 12,13 : no hemorrhage (score 0); evidence of slightly hypointense T2* signal (score 1); single punctate hemorrhage with high-contrast, hypointense T2* signal of Ͻ4 mm 2 diameter (score 2); multiple punctate hemorrhages with highcontrast, hypointense T2* signal Ͻ4 mm 2 diameter (score 3); and large hemorrhage defined by high-contrast, hypointense T2* signal Ͼ4 mm 2 diameter (score 4). In our previous studies, hemoglobin volume as well as macroscopic bleeding on unstained coronal cryosections corresponded well with the hypointense area on T2* MRI.…”

“…In our previous studies, hemoglobin volume as well as macroscopic bleeding on unstained coronal cryosections corresponded well with the hypointense area on T2* MRI. 12,13 In animals that died prematurely (ie, before the 24-hour MRI), scoring of hemorrhage was performed on unstained coronal cryosections according to MRI criteria. Hemorrhage scoring of T2* images was performed by 2 independent observers with good interrater reliability (ϭ0.81; PϽ0.001; interrater reliability analysis, SPSS).…”

Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: A Review

“…However, as a promising nondrug and noninvasive treatment, HBO is still used in basic research and clinical studies of brain ischemia, especially with the extensive application of imaging technology, such as neuroimaging facilities (CT, SPECT and MRI), which provides an opportunity for early diagnosis and timely HBO treatment of AIS. Furthermore, HBO combined with thrombolysis seems promising in reducing secondary hemorrhage of ischemic stroke patients [103] , which is worthy of further studies.…”