Comparative Studies of Cerebral Reperfusion Injury in the Posterior and Anterior Circulations After Mechanical Thrombectomy

Cerebral reperfusion injury is the major complication of mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Contrast extravasation (CE) and intracranial hemorrhage (ICH) are the key radiographical features of cerebral reperfusion injury. The aim of this study was to investigate CE and ICH after MT in the anterior and posterior circulation, and their effect on functional outcome. This is a retrospective study of all consecutive patients who were treated with MT for AIS at University of California Irvine Medical Center between January 1, 2014, and December 31, 2017. Patient characteristics, clinical features, procedural variables, contrast extravasation, ICH, and outcomes after MT were analyzed. A total of 131 patients with anterior circulation (AC) stroke and 25 patients with posterior circulation (PC) stroke underwent MT during the study period. There was no statistically significant difference in admission NIHSS score, blood pressure, rate of receiving intravenous tPA, procedural variables, contrast extravasation, and symptomatic ICH between the 2 groups. Patients with PC stroke had a similar rate of favorable outcome (mRS 0–2) but significantly higher mortality (40.0% vs. 10.7%, p < 0.01) than patients with AC stroke. Multivariate regression analysis identified initial NIHSS score (OR 1.1, CI 1.0–1.2, p = 0.01), number of passes with stent retriever (OR 2.1, CI 1.3–3.6, p < 0.01), and PC stroke (OR 9.3, CI 2.5–35.1, p < 0.01) as independent risk factors for death. There was no significant difference in functional outcomes between patients with and without evidence of cerebral reperfusion injury after MT. We demonstrated that AC and PC stroke had similar rates of cerebral reperfusion injury and favorable outcome after MT. Cerebral reperfusion injury is not a significant independent risk factor for poor functional outcome.

Astrocytic A1/A2 paradigm participates in glycogen mobilization mediated neuroprotection on reperfusion injury after ischemic stroke

Background Astrocytic glycogen works as an essential energy reserve for surrounding neurons and is reported to accumulate excessively during cerebral ischemia/reperfusion (I/R) injury. Our previous study found that accumulated glycogen mobilization exhibits a neuroprotective effect against I/R damage. In addition, ischemia could transform astrocytes into A1-like (toxic) and A2-like (protective) subtypes. However, the underlying mechanism behind accumulated glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury and its relationship with the astrocytic A1/A2 paradigm is unknown. Methods Astrocytic glycogen phosphorylase, the rate-limiting enzyme in glycogen mobilization, was specifically overexpressed and knocked down in mice and in cultured astrocytes. The I/R injury was imitated using a middle cerebral artery occlusion/reperfusion model in mice and an oxygen–glucose deprivation/reoxygenation model in cultured cells. Alterations in A1-like and A2-like astrocytes and the expression of phosphorylated nuclear transcription factor-κB (NF-κB) and phosphorylated signal transducer and activator of transcription 3 (STAT3) were determined by RNA sequencing, immunofluorescence and immunoblotting. Metabolites, including glycogen, NADPH, glutathione and reactive oxygen species (ROS), were analyzed by biochemical analysis. Results Here, we observed that astrocytic glycogen mobilization inhibited A1-like astrocytes and enhanced A2-like astrocytes after reperfusion in an experimental ischemic stroke model in vivo and in vitro. In addition, glycogen mobilization could enhance the production of NADPH and glutathione by the pentose phosphate pathway (PPP) and reduce ROS levels during reperfusion. NF-κB inhibition and STAT3 activation caused by a decrease in ROS levels were responsible for glycogen mobilization-induced A1-like and A2-like astrocyte transformation after I/R. The astrocytic A1/A2 paradigm is closely correlated with glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury. Conclusions Our data suggest that ROS-mediated NF-κB inhibition and STAT3 activation are the key pathways for glycogen mobilization-induced neuroprotection and provide a promising metabolic target for brain reperfusion injury in ischemic stroke.