Dataset Information

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

ABSTRACT: Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm³ absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

SUBMITTER: Beretta S

PROVIDER: S-EPMC5624388 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

Beretta Simone S Versace Alessandro A Carone Davide D Riva Matteo M Dell'Era Valentina V Cuccione Elisa E Cai Ruiyao R Monza Laura L Pirovano Silvia S Padovano Giada G Stiro Fabio F Presotto Luca L Paternò Giovanni G Rossi Emanuela E Giussani Carlo C Sganzerla Erik P EP Ferrarese Carlo C

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20170123 10

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascu ...[more]

PMID: 28112023

Similar Datasets

Project description:Background: The contribution of metabolic profile to the cerebral collateral circulation in acute ischemic stroke (AIS) has not been fully outlined. In this study, we conducted a metabolomic study to assess the relationship between the metabolic biomarkers and the collateral status of AIS. Methods: A two-stage study was conducted from September 2019 to June 2021 in our hospital. There were 96 subjects including 66 patients with AIS and 30 healthy controls in the discovery stage and 80 subjects including 53 patients with AIS and 27 healthy controls in the validation stage. Collateral circulation was assessed by the Tan score based on computed tomographic angiography (CTA). Liquid chromatography-tandem mass spectrometry was used to identify differential metabolic markers. Then, an ELISA was employed to detect the plasma levels of sphingosine-1-phosphate (S1P). Results:There were 114 differential metabolites between patients with AIS and control groups and 37 differential metabolites between good collateral circulation (GCC) and poor collateral circulation (PCC) groups. The pathway enrichment analysis revealed that arginine biosynthesis was the only statistically significant pathway between AIS and control groups and sphingolipid metabolism was the only statistically significant pathway between GCC and PCC groups. The differential metabolites sphinganine-1-phosphate (SA1P) and S1P belong to the sphingolipid metabolism. In the discovery stage, when the GCC group was compared with the PCC group, the receiver operating characteristic (ROC) analysis showed that plasma SA1P relative levels demonstrated an area under the curve (AUC) of 0.719 (95% CI: 0.582-0.834), and S1P levels demonstrated an AUC of 0.701 (95% CI: 0.567-0.819). In addition, both plasma SA1P and S1P relative levels showed significant negative correlations with the 90-day modified Rankin Scale (mRS) score. In the validation sample, higher plasma S1P levels were independent predictors of GCC (p = 0.014), and plasma S1P levels demonstrated an AUC of 0.738 (95% CI: 0.599-0.849) to differentiate patients with GCC from patients with PCC. In addition, plasma S1P levels also showed significant negative correlations with the 90-day mRS score. Conclusion: We first illustrated the association between plasma metabolic profiles and cerebral collateral circulation in patients with AIS. Plasma S1P levels might be a potential diagnostic biomarker for predicting collateral circulation status in patients with AIS.

Project description:BackgroundMixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial.MethodsIn this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment. The primary analysis assessed the degree to which collateral status modified the effect between treatment group and functional outcome as defined by the 90-day modified Rankin Scale score. Logistic regression was used to model the data, with adjustments made for thrombectomy status, age, post-perfusion thrombolysis in cerebral infarction (TICI) score, tissue plasminogen activator (tPA) use, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Five SHINE trial centers contributed data for this analysis. Statistical significance was defined as a p-value < 0.05.ResultsAmong the 1151 patients in the SHINE trial, 57 with angiographic data were included in this sub-analysis, of whom 19 had poor collaterals and 38 had good collaterals. While collateral status had no effect (p = 0.855) on the association between glucose control treatment group and functional outcome, patients with good collaterals were more likely to have a favorable functional outcome (p = 0.001, OR 5.02; 95% CI 1.37-16.0).ConclusionsIn a post-hoc analysis using a subset of patients with angiographic data enrolled in the SHINE trial, collateral status did not modify the association between glucose control treatment group and functional outcome. However, consistent with prior studies, there was a significant association between good collateral status and favorable outcome in patients with large vessel occlusion stroke.Trial registrationClinicalTrials.gov Identifier is NCT01369069. Registration date is June 8, 2011.

Dataset Information

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

Publications

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets