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Targeting the HIV-infected brain to improve ischemic stroke outcome.

ABSTRACT: HIV-associated cerebrovascular events remain highly prevalent even in the current era of antiretroviral therapy (ART). We hypothesize that low-level HIV replication and associated inflammation endure despite antiretroviral treatment and affect ischemic stroke severity and outcomes. Using the EcoHIV infection model and the middle cerebral artery occlusion as the ischemic stroke model in mice, we present in vivo analysis of the relationship between HIV and stroke outcome. EcoHIV infection increases infarct size and negatively impacts tissue and functional recovery. Ischemic stroke also results in an increase in EcoHIV presence in the affected regions, suggesting post-stroke reactivation that magnifies pro-inflammatory status. Importantly, ART with a high CNS penetration effectiveness (CPE) is more beneficial than low CPE treatment in limiting tissue injury and accelerating post-stroke recovery. These results provide potential insight for treatment of HIV-infected patients that are at risk of developing cerebrovascular disease, such as ischemic stroke.

SUBMITTER: Bertrand L

PROVIDER: S-EPMC6494822 | biostudies-other | 2019 May

REPOSITORIES: biostudies-other

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Targeting the HIV-infected brain to improve ischemic stroke outcome.

Bertrand Luc L Méroth Fannie F Tournebize Marie M Leda Ana Rachel AR Sun Enze E Toborek Michal M

Nature communications 20190501 1

HIV-associated cerebrovascular events remain highly prevalent even in the current era of antiretroviral therapy (ART). We hypothesize that low-level HIV replication and associated inflammation endure despite antiretroviral treatment and affect ischemic stroke severity and outcomes. Using the EcoHIV infection model and the middle cerebral artery occlusion as the ischemic stroke model in mice, we present in vivo analysis of the relationship between HIV and stroke outcome. EcoHIV infection increase ...[more]

PMID: 31043599

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Project description:Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS). Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups. Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52-6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24-5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47-7.52, p = 0.570). Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.

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Targeting the HIV-infected brain to improve ischemic stroke outcome.

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Targeting the HIV-infected brain to improve ischemic stroke outcome.

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