Dataset Information

Delayed Effects of Acute Reperfusion on Vascular Remodeling and Late-Phase Functional Recovery After Stroke.

ABSTRACT: Tissue perfusion is a necessary condition for vessel survival that can be compromised under ischemic conditions. Following stroke, delayed effects of early brain reperfusion on the vascular substrate necessary for remodeling, perfusion and maintenance of proper peri-lesional hemodynamics are unknown. Such aspects of ischemic injury progression may be critical for neurological recovery in stroke patients. This study aims to describe the impact of early, non-thrombolytic reperfusion on the vascular brain component and its potential contribution to tissue remodeling and long-term functional recovery beyond the acute phase after stroke in 3-month-old male C57bl/6 mice. Permanent (pMCAO) and transient (60 min, tMCAO) brain ischemia mouse models were used for characterizing the effect of early, non-thrombolytic reperfusion on the brain vasculature. Analysis of different vascular parameters (vessel density, proliferation, degeneration and perfusion) revealed that, while early middle cerebral artery recanalization was not sufficient to prevent sub-acute vascular degeneration within the ischemic brain regions, brain reperfusion promoted a secondary wave of vascular remodeling in the peri-lesional regions, which led to improved perfusion of the ischemic boundaries and late-phase neurological recovery. This study concluded that acute, non-thrombolytic artery recanalization following stroke favors late-phase vascular remodeling and improves peri-lesional perfusion, contributing to secondary functional recovery.

SUBMITTER: Duran-Laforet V

PROVIDER: S-EPMC6664024 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Delayed Effects of Acute Reperfusion on Vascular Remodeling and Late-Phase Functional Recovery After Stroke.

Durán-Laforet Violeta V Fernández-López David D García-Culebras Alicia A González-Hijón Juan J Moraga Ana A Palma-Tortosa Sara S García-Yébenes Isaac I Vega-Pérez Adrián A Lizasoain Ignacio I Moro María Ángeles MÁ

Frontiers in neuroscience 20190723

Tissue perfusion is a necessary condition for vessel survival that can be compromised under ischemic conditions. Following stroke, delayed effects of early brain reperfusion on the vascular substrate necessary for remodeling, perfusion and maintenance of proper peri-lesional hemodynamics are unknown. Such aspects of ischemic injury progression may be critical for neurological recovery in stroke patients. This study aims to describe the impact of early, non-thrombolytic reperfusion on the vascula ...[more]

PMID: 31396042

Similar Datasets

Project description:BACKGROUND:Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a transvalvular axial-flow pump in the left ventricle and delaying myocardial reperfusion, known as primary unloading, limits infarct size after AMI. The mechanisms underlying the cardioprotective benefit of primary unloading and whether the acute decrease in infarct size results in a durable reduction in LV scar and improves cardiac function remain unknown. OBJECTIVES:This study tested the importance of LV unloading before reperfusion, explored cardioprotective mechanisms, and determined the late-term impact of primary unloading on myocardial function. METHODS:Adult male swine were subjected to primary reperfusion or primary unloading after 90 min of percutaneous left anterior descending artery occlusion. RESULTS:Compared with primary reperfusion, 30 min of LV unloading was necessary and sufficient before reperfusion to limit infarct size 28 days after AMI. Compared with primary reperfusion, primary unloading increased expression of genes associated with cellular respiration and mitochondrial integrity within the infarct zone. Primary unloading for 30 min further reduced activity levels of proteases known to degrade the cardioprotective cytokine, stromal-derived factor (SDF)-1?, thereby increasing SDF-1? signaling via reperfusion injury salvage kinases, which limits apoptosis within the infarct zone. Inhibiting SDF-1? activity attenuated the cardioprotective effect of primary unloading. Twenty-eight days after AMI, primary unloading reduced LV scar size, improved cardiac function, and limited expression of biomarkers associated with heart failure and maladaptive remodeling. CONCLUSIONS:The authors report for the first time that first mechanically reducing LV work before coronary reperfusion with a transvalvular pump is necessary and sufficient to reduce infarct size and to activate a cardioprotective program that includes enhanced SDF-1? activity. Primary unloading further improved LV scar size and cardiac function 28 days after AMI.

Project description:BACKGROUND AND PURPOSE:Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. METHODS:We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively. RESULTS:We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). CONCLUSIONS:Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time. RESULTS:in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Dataset Information

Delayed Effects of Acute Reperfusion on Vascular Remodeling and Late-Phase Functional Recovery After Stroke.

Publications

Delayed Effects of Acute Reperfusion on Vascular Remodeling and Late-Phase Functional Recovery After Stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets