Risultati per: Come stress e attacchi di cuore sono collegati

Stroke, Volume 53, Issue Suppl_1, Page AWP252-AWP252, February 1, 2022. Introduction:Tamoxifen (TAM), a selective estrogen receptor modifier, is a first-line treatment option for hormone receptor positive breast cancer. TAM inhibits the downstream estrogen receptor signaling in tumor cells. Stroke risk is increased in women with low estrogen levels, such as early-onset menopause, and doubles in women after the age of 55, which corresponds with the average age of menopause. Women with breast cancer who were treated with tamoxifen had an increased risk for ischemic stroke (82%). Since stroke severity is associated with increased blood brain barrier (BBB) damage, we investigated the effects of tamoxifen on activation and mitochondrial stress in astrocytes, which is a cellular component of the BBB.Methods:Cultured female human astrocytes were treated with tamoxifen (1uM), 17ß-estradiol (10nM), or vehicle (DMSO) for 24 hours. Cells were separated into two groups: normoxic (21% O2, 25mM glucose) or oxygen and glucose deprivation (OGD) conditions 6 hours before analysis. ROS production was measured using the Cellular ROS Assay Kit (Red) and aquaporin-4 levels were visualized via immunocytochemistry. Mitochondrial function was assessed by using a Seahorse XFe96 Analyzer.Results:Tamoxifen treatment increased Aquaporin-4 protein levels (p

Stroke, Volume 53, Issue Suppl_1, Page AWP217-AWP217, February 1, 2022. Introduction:Ischemic stroke is the leading cause of death and disability worldwide. It was recently reported that mental stress could aggravate stroke damage. However, the causal relationship between mental stress and stroke outcomes remained unclear. In current study, we determined whether mitochondria dysfunction was induced by mental stress and thus enhanced brain damage after ischemic stroke. The translocator protein (TSPO) is a transmembrane protein located on the outer mitochondria membrane (OMM) and induced mitochondrial dysfunction. This study focused on the key role of TSPO in stress aggravated ischemia/reperfusion injury.Methods:Six-week-old male C57BL/6J mice were divided into four groups: control, chronic restraint stress (CRS), TSPO antagonist (PK11195, 3mg/kg, i.p.) and TSPO antagonist+CRS. Mice in CRS were placed in ventilated 50mL tubes 6 hours/day for 28 days. On the day 29th, behavioral tests were conducted to measure the depressive-like levels. Mice then were subjected to middle cerebral artery occlusion (MCAO). At 6/24 hours after MCAO, TTC staining and modified scoring systems were applied to analyze infarct volume and neurological deficits, and the expression of TSPO was detected using immunofluorescence. Apoptotic cell death and apoptotic proteins (Bcl-2, Bax and caspase-3/9) were measured by TUNEL and Western blot. Effects of TSPO on mitochondrial membrane potential (MMP) and mito-ROS were measured by JC-1 staining and live cell imaging dyes (mitoSOX and DCFDA)in vitro.Results:As depressive model, CRS aggravated infarct volume and neurological deficits after MCAO, with increased levels of apoptosis (cell death and protein expressions), in association with increased TSPO levels. TSPO antagonist could decrease stress-aggravated stroke injury and apoptotic cell death, indicating TSPO was involved in stress related stroke outcomes.In vitro, MMP was increased and mito-ROS was decreased after TSPO siRNA transfection, suggesting TSPO may induce mitochondria deficits through producing more mito-ROS.Conclusions:Mental stress by CRS exacerbated ischemic injury after stroke. Importantly, the results showed that TSPO may play a key role in inducing mitochondrial dysfunction in stress-aggravated stroke damage.

Stroke, Ahead of Print. Background and Purpose:Chronic hypoxia-ischemia is a putative mechanism underlying the development of white matter hyperintensities (WMH) and microstructural disruption in cerebral small vessel disease. WMH fall primarily within deep white matter (WM) watershed regions. We hypothesized that elevated oxygen extraction fraction (OEF), a signature of hypoxia-ischemia, would be detected in the watershed where WMH density is highest. We further hypothesized that OEF would be elevated in regions immediately surrounding WMH, at the leading edge of growth.Methods:In this cross-sectional study conducted from 2016 to 2019 at an academic medical center in St Louis, MO, participants (age >50) with a range of cerebrovascular risk factors underwent brain magnetic resonance imaging using pseudocontinuous arterial spin labeling, asymmetric spin echo, fluid-attenuated inversion recovery and diffusion tensor imaging to measure cerebral blood flow (CBF), OEF, WMH, and WM integrity, respectively. We defined the physiologic watershed as a region where CBF was below the 10th percentile of mean WM CBF in a young healthy cohort. We conducted linear regression to evaluate the relationship between CBF and OEF with structural and microstructural WM injury defined by fluid-attenuated inversion recovery WMH and diffusion tensor imaging, respectively. We conducted ANOVA to determine if OEF was increased in proximity to WMH lesions.Results:In a cohort of 42 participants (age 50–80), the physiologic watershed region spatially overlapped with regions of highest WMH lesion density. As CBF decreased and OEF increased, WMH density increased. Elevated watershed OEF was associated with greater WMH burden and microstructural disruption, after adjusting for vascular risk factors. In contrast, WM and watershed CBF were not associated with WMH burden or microstructural disruption. Moreover, OEF progressively increased while CBF decreased, in concentric contours approaching WMH lesions.Conclusions:Chronic hypoxia-ischemia in the watershed region may contribute to cerebral small vessel disease pathogenesis and development of WMH. Watershed OEF may hold promise as an imaging biomarker to identify individuals at risk for cerebral small vessel disease progression.

L’impatto psicologico della pandemia sugli operatori sanitari è stato considerevole. Al prolungarsi della pandemia il rischio è che lo stress cronicizzi, determinando sindromi da burn-out. Azioni di tutela sono essenziali per prevenire queste problematiche.