Dataset Information

Upregulation of AQP4 Improves Blood-Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage.

ABSTRACT: In intracerebral hemorrhage (ICH), delayed secondary neural damages largely occur from perihematomal edema (PHE) resulting from the disruption of the blood-brain barrier (BBB). PHE is often considered the principal cause of morbidity and mortality in patients with ICH. Nevertheless, the main cellular mechanism as well as the specific BBB component involved in the formation of PHE after ICH remains elusive. Herein, we evaluated the role of AQP4, a water channel expressed on the astrocytes of the BBB, in the formation of PHE in ICH. The static and dynamic functions of the BBB were evaluated by analyzing the microstructure and leakage assay. Protein changes in the PHE lesion were analyzed and the control mechanism of AQP4 expression by reactive oxygen species was also investigated. Delayed PHE formation due to BBB disruption after ICH was confirmed by the decreased coverage of multiple BBB components and increased dynamic leakages. Microstructure assay showed that among the BBB components, AQP4 showed a markedly decreased expression in the PHE lesions. The decrease in AQP4 was due to microenvironmental ROS derived from the hemorrhage and was restored by treatment with ROS scavenger. AQP4-deficient mice had significantly larger PHE lesions and unfavorable survival outcomes compared with wild-type mice. Our data identify AQP4 as a specific BBB-modulating target for alleviating PHE in ICH. Further comprehensive studies are needed to form the preclinical basis for the use of AQP4 enhancers as BBB modulators for preventing delayed cerebral edema after ICH.

SUBMITTER: Jeon H

PROVIDER: S-EPMC8804112 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Upregulation of AQP4 Improves Blood-Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage.

Jeon Hanwool H Kim Moinay M Park Wonhyoung W Lim Joon Seo JS Lee Eunyeup E Cha Hyeuk H Ahn Jae Sung JS Kim Jeong Hoon JH Hong Seok Ho SH Park Ji Eun JE Lee Eun-Jae EJ Woo Chul-Woong CW Lee Seungjoo S

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20210920 4

In intracerebral hemorrhage (ICH), delayed secondary neural damages largely occur from perihematomal edema (PHE) resulting from the disruption of the blood-brain barrier (BBB). PHE is often considered the principal cause of morbidity and mortality in patients with ICH. Nevertheless, the main cellular mechanism as well as the specific BBB component involved in the formation of PHE after ICH remains elusive. Herein, we evaluated the role of AQP4, a water channel expressed on the astrocytes of the ...[more]

PMID: 34545550

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Project description:Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement. Methods- Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion. Results- Patients with cancer (N=80) and controls (N=136) had similar demographics (all P>0.20), although hypertension was more prevalent among controls (P=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500-211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; P=1.88×10-9) and PHE-to-ICH volume ratios (2.26 versus 0.99; P=2.20×10-16). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (β=1.29 [95% CI, 1.58-1.30] P=1.30×10-5) and platelet transfusion (β=15.67 [95% CI, 3.61-27.74] P=0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03-1.10] P=6.76×10-5), PHE volume (odds ratio, 1.07 [95% CI, 1.04-1.09] P=7.40×10-6), PHE growth (odds ratio, 1.05 [95% CI, 1.01-1.10] P=0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22-1.79] P=0.0001). Conclusions- Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.

Dataset Information

Upregulation of AQP4 Improves Blood-Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage.

Publications

Upregulation of AQP4 Improves Blood-Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage.

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