Dataset Information

Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage.

ABSTRACT:

Objective

This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy.

Methods

The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.

Results

Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p = 0.004). BBB disruption on the pretreatment scan was associated with PH (p = 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified.

Conclusions

The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment.

SUBMITTER: Leigh R

PROVIDER: S-EPMC4955280 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and Purpose- The high prevalence of hyperintense acute reperfusion marker (HARM) seen after endovascular therapy is suggestive of blood-brain barrier disruption and hemorrhage risk and may be attributable to multiple thrombectomy passes needed to achieve recanalization. Methods- Patients with acute stroke were included if they were screened from January 2015 through February 2019, received an acute ischemic stroke diagnosis involving the anterior circulation, treated with or without IV tPA (intravenous tissue-type plasminogen activator), consented to the NINDS Natural History Study, and imaged with a baseline magnetic resonance imaging before receiving endovascular therapy. Consensus image reads for HARM and hemorrhagic transformation were performed. Good clinical outcome was defined as 0-2 using the latest available modified Rankin Scale score. Results- Eighty patients met all study criteria and were included in the analyses. Median age was 65 years, 64% female, 51% black/African American, median admit National Institutes of Health Stroke Scale=19, 56% treated with IV tPA, and 84% achieved Thrombolysis in Cerebral Infarction score of 2b/3. Multiple-pass patients had significantly higher rates of severe HARM at 24 hours (67% versus 29%; P=0.001), any hemorrhagic transformation (60% versus 36%; P=0.04) and poor clinical outcome (67% versus 36%; P=0.008). Only age (odds ratio, 1.1; 95% CI, 1.01-1.12; P=0.022) and severe HARM at 24 hours post-endovascular therapy were significantly associated with multiple passes (odds ratio, 7.2; 95% CI, 1.93-26.92; P=0.003). Conclusions- In this exploratory study, multiple thrombectomy passes are independently associated with a significant increase in blood-brain barrier disruption detected at 24 hours. Patients with HARM post-endovascular therapy had a >7-fold increase in the odds of having multiple- versus single-pass thrombectomy. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Project description:Disruption of the blood-brain barrier (BBB) and the subsequent formation of brain edema is the most severe consequence of intracerebral hemorrhage (ICH), leading to drastic neuroinflammatory responses and neuronal cell death. A better understanding of ICH pathophysiology to develop effective therapy relies on selecting appropriate animal models. The collagenase injection ICH model and the autologous arterial whole blood infusion ICH model have been developed to investigate the pathophysiology of ICH. However, it remains unclear whether the temporal progression and the underlying mechanism of BBB breakdown are similar between these two ICH models. In this study, we aimed to determine the progression and the mechanism of BBB disruption via the two commonly used murine ICH models: the collagenase-induced ICH model (c-ICH) and the double autologous whole blood ICH model (b-ICH). Intrastriatal injection of 0.05 U collagenase or 20 μL autologous blood was used for a comparable hematoma volume in these two ICH models. Then we analyzed BBB permeability using Evan's blue and IgG extravasation, evaluated tight junction (TJ) damage by transmission electron microscope (TEM) and Western blotting, and assessed matrix metalloproteinase-9 (MMP-9) activity and aquaporin 4 (AQP4) mRNA expression by Gelatin gel zymography and RT-PCR, respectively. The results showed that the BBB leakage was associated with a decrease in TJ protein expression and an increase in MMP-9 activity and AQP4 expression on day 3 in the c-ICH model compared with that on day 5 in the b-ICH model. Additionally, using TEM, we found that the TJ was markedly damaged on day 3 in the c-ICH model compared with that on day 5 in the b-ICH model. In conclusion, the BBB was disrupted in the two ICH models; compared to the b-ICH model, the c-ICH model presented with a more pronounced disruption of BBB at earlier time points, suggesting that the c-ICH model might be a more suitable model for studying early BBB damage and protection after ICH.