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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.

SUBMITTER: Sun L

PROVIDER: S-EPMC2949252 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia.

Sun Li L Zhou Wei W Mueller Christian C Sommer Clemens C Heiland Sabine S Bauer Alexander T AT Marti Hugo H HH Veltkamp Roland R

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20100428 9

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 ...[more]

PMID: 20424638

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Project description:BackgroundExacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation.MethodsMice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 h of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 min. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 h.ResultsPlatelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia.ConclusionOur findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

Project description:ObjectiveElevated ICP is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Delayed cerebral ischemia (DCI) is the most important reason for a poor clinical outcome after a subarachnoid hemorrhage. DCI is understood as a multifactorial process that evolves over time, largely caused by the sequelae of increased intracranial pressure (ICP). The study aimed to assess how to better define the association between ICP and DCI, and whether rational ICP management can improve the outcome of aSAH patients.MethodsWe prospectively reviewed patients diagnosed with aSAH and received microsurgery clipping at our department from December 2019 to January 2021. Subdural ICP monitoring devices were kept to monitor the ICP. The ICP values were recorded every 1-h epochs. ICP -guided dehydration treatments were routinely performed to control the ICP level of patients after surgery. To evaluate whether the subdural ICP-directed management improved the prognosis of the aSAH patients, we compared the outcome data of the patients in our cohort with those treated at another ward of our hospital at the same period.ResultsIn total, 144 consecutive aSAH patients received microsurgery clipping at our department, 68 of whom underwent ICP monitoring. A total of 11,424 1-h ICP measurements were recorded for the included patients (1.30 years of recordings). Of 68 patients with ICP monitoring, 27 (27/68, 39.7%) patients developed DCI. Univariate analysis showed that higher Hunt-Hess grade (OR 2.138, 95% CI 1.025-4.459, p = 0.043), higher preoperative modified Rankin Scale score (OR 1.534, 95% CI 1.033-2.276, p = 0.034), and the max ICP value of each day value >28.5 mmHg (OR 4.442, 95% CI 1.509-13.082, p = 0.007) were associated with DCI. Also, patients with ICP-directed treatment showed a significantly lower DCI incidence than patients without ICP monitoring.ConclusionOur study suggests that I less than 15 mmHg possibly constitute normal values and that 28.5 mmHg is the ICP threshold most strongly associated with the occurrence of DCI in aSAH patients. Patients who received the ICP-directed treatment presented a lower incidence of DCI. Our findings provide a basis for the recommendation of ICP-directed treatment after aSAH.Trial registration numberNCT04785976.

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Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia.

Publications

Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia.

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