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Reperfusion after ischemic stroke is associated with reduced brain edema.

ABSTRACT: Rapid revascularization is highly effective for acute stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. We investigated the relationship between reperfusion and edema in patients from the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohorts. Reperfusion percentage was measured as the difference in perfusion-weighted imaging lesion volume between baseline and follow-up (day 3-5 for EPITHET; day 6-8 for MR RESCUE). Midline shift (MLS) and swelling volume were quantified on follow-up MRI. We found that reperfusion was associated with less MLS (EPITHET: Spearman ρ = -0.46; P < 0.001, and MR RESCUE: Spearman ρ = -0.49; P < 0.001) and lower swelling volume (EPITHET: Spearman ρ = -0.56; P < 0.001, and MR RESCUE: Spearman ρ = -0.27; P = 0.026). Multivariable analyses performed in EPITHET and MR RESCUE demonstrated that reperfusion independently predicted both less MLS (ß coefficient = -0.056; P = 0.025, and ß coefficient = -0.38; P = 0.028, respectively) and lower swelling volumes (ß coefficient = -4.7; P = 0.007, and ß coefficient = -10.7; P = 0.009, respectively), after adjusting for age, sex, NIHSS, admission glucose and follow-up lesion size. Taken together, our data suggest that even modest improvement in perfusion is associated with less brain edema in EPITHET and MR RESCUE.

SUBMITTER: Irvine HJ

PROVIDER: S-EPMC6168909 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Reperfusion after ischemic stroke is associated with reduced brain edema.

Irvine Hannah J HJ Ostwaldt Ann-Christin AC Bevers Matthew B MB Dixon Simone S Battey Thomas Wk TW Campbell Bruce Cv BC Davis Stephen M SM Donnan Geoffrey A GA Sheth Kevin N KN Jahan Reza R Saver Jeffrey L JL Kidwell Chelsea S CS Kimberly W Taylor WT

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20170721 10

Rapid revascularization is highly effective for acute stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. We investigated the relationship between reperfusion and edema in patients from the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohorts. Reperfusion percentage was measured as the difference in perfusion-weighted imaging lesion volume between ba ...[more]

PMID: 28731381

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Project description:ImportanceIt is uncertain whether therapeutic reperfusion with endovascular treatment yields more or less brain edema.ObjectiveTo elucidate the association between reperfusion and brain edema. The secondary objectives were to evaluate whether brain edema could partially be responsible for worse outcomes in patients with later reperfusion or lower Alberta Stroke Program Early Computed Tomography Score.Design, setting, and participantsThis was a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective, randomized, multicenter clinical trial of endovascular treatment compared with conventional care of patients with acute anterior circulation ischemic stroke. Of 502 patients enrolled from December 2010 to June 2014, 2 patients declined to participate. Additionally, exclusion criteria were absence of follow-up imaging or presence of parenchymal hematoma, resulting in 462 patients included in this study. Brain edema was assessed retrospectively, from December 10, 2016, to July 24, 2017, by measuring midline shift (MLS) in all available follow-up scans. Observers were blinded to clinical data.Main outcomes and measuresMidline shift was assessed as present or absent and as a continuous variable. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction score in the endovascular treatment arm. The modified arterial occlusive lesion score was used to evaluate the recanalization status in both arms. The modified Rankin scale score at 90 days was used for functional outcome.ResultsOf 462 patients, the mean (SD) age was 65 (11) years, and 41.8% (n = 193) were women. Successful reperfusion and recanalization were associated with a reduced likelihood of having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P < .001 and adjusted common odds ratio, 0.34; 95% CI, 0.21-0.55; P < .001, respectively). Midline shift was partially responsible for worse modified Rankin scale scores in patients without reperfusion or recanalization (MLS changed the logistic regression coefficients by 30.3% and 12.6%, respectively). In patients with delayed reperfusion or lower Alberta Stroke Program Early Computed Tomography Score, MLS mediated part of the worse modified Rankin scale scores, corresponding to a change in the regression coefficient of 33.3% and 64.2%, respectively.Conclusions and relevanceSuccessful reperfusion was associated with reduced MLS. This study identifies an additional benefit of reperfusion in relation to edema, as well as rescuing ischemic brain tissue at risk for infarction.Trial registrationNetherlands Trial Registry number: NTR1804 and Current Controlled Trials number: ISRCTN10888758.

Project description:Background: Thrombolysis with tissue plasminogen activator (tPA) remains the only approved drug therapy for acute ischemic stroke. However, delayed tPA treatment is associated with an increased risk of brain hemorrhage. In this study, we assessed whether QiShenYiQi (QSYQ), a compound Chinese medicine, can attenuate tPA-induced brain edema and hemorrhage in an experimental stroke model. Methods: Male mice were subjected to ferric chloride-induced carotid artery thrombosis followed by mechanical detachment of thrombi. Then mice were treated with QSYQ at 2.5 h followed by administration of tPA (10 mg/kg) at 4.5 h. Hemorrhage, infarct size, neurological score, cerebral blood flow, Evans blue extravasation, FITC-labeled albumin leakage, tight and adherens junction proteins expression, basement membrane proteins expression, matrix metalloproteinases (MMPs) expression, leukocyte adhesion, and leukocyte infiltration were assessed 24 h after tPA administration. Results: Compared with tPA alone treatments, the combination therapy of QSYQ and tPA significantly reduced hemorrhage, infarction, brain edema, Evans blue extravasation, albumin leakage, leukocyte adhesion, MMP-9 expression, and leukocyte infiltration at 28.5 h after stroke. The combination also significantly improved the survival rate, cerebral blood flow, tight and adherens junction proteins (occludin, claudin-5, junctional adhesion molecule-1, zonula occludens-1, VE-cadherin, α-catenin, β-catenin) expression, and basement membrane proteins (collagen IV, laminin) expression. Addition of QSYQ protected the downregulated ATP 5D and upregulated p-Src and Caveolin-1 after tPA treatment. Conclusion: Our results show that QSYQ inhibits tPA-induced brain edema and hemorrhage by protecting the blood-brain barrier integrity, which was partly attributable to restoration of energy metabolism, protection of inflammation and Src/Caveolin signaling activation. The present study supports QSYQ as an effective adjunctive therapy to increase the safety of delayed tPA thrombolysis for ischemic stroke.

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Reperfusion after ischemic stroke is associated with reduced brain edema.

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Reperfusion after ischemic stroke is associated with reduced brain edema.

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