Risultati per: Come stress e attacchi di cuore sono collegati

Stroke, Volume 55, Issue Suppl_1, Page AWMP63-AWMP63, February 1, 2024. Introduction:Physiological imaging studies in patients with severe steno-occlusive carotid disease (SSCD) reveal hemodynamic compromise as a mechanism underlying watershed infarcts (WI). However, it is unclear if the watershed region (WR) is intrinsically vulnerable in healthy individuals. We measured cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in healthy individuals to determine if the WR was under metabolic stress, and therefore an intrinsically vulnerable region.Methods:To define a common WR, we created an “average WI density map” using MRIs from patients with diffusion restriction ipsilateral to SSCD from a single academic center (7/10 to 8/20). WI density maps were created using 5%, 10% and 15% incidence thresholds. Maps were overlaid onto coregistered CBF and OEF maps generated from pseudo-continuous arterial spin labeling (pCASL) and asymmetric spin echo sequences, respectively, performed on healthy controls aged

Stroke, Volume 55, Issue Suppl_1, Page AWP233-AWP233, February 1, 2024. Introduction:Mental stress was linked with adverse outcomes following ischemic stroke. Accumulation of lactate due to mental stress is well-documented, especially in skeletal muscles. Importantly, lactate serves as a key substrate for lactylation, a novel post-translational protein modification, which triggers mitochondrial fission. This study investigates the pivotal role of histone lactylation in driving neuronal mitochondrial fission, which may amplify the detrimental outcomes of stroke under mental stress.Methods:A total of 120 C57BL/6J mice were divided into four groups: control, chronic restraint stress (CRS), lactylationantagonist (C646, 10mg/kg, i.p.) and C646+CRS. CRS for mice was induced in a 50mL tube for 6 hours per day for consecutive 28 days. On the day 29th, Western blot was applied to detect the expression of fission related proteins (DRP1, MFF and FIS1). The effects of lactylation on mitochondria function was determined through JC-1 and mitoSOX™ staining by adding exogenous lactate (10mM) and C646 (20mM) in neuronal cells. The stressed mice then were subjected to 45 minute-middle-cerebral -artery-occlusion (MCAO). At 6 and 24 hours of reperfusion, apoptotic cell death and apoptotic proteins (Bcl-2, BAX and cleaved caspase-3) were measured by TUNEL and Western blot. Infarct volume and neurological deficits were determined by TTC staining and scoring systems at 48 hours of reperfusion.Results:CRS aggravated ischemic injury and apoptosis after stroke. C646, a lactylation antagonist, significantly decreased protein expressions of DRP1, MFF and FIS1 and reversed CRS-associated stroke injury. Furthermore, mitochondria membrane potential (MMP) was decreased and ROS was increased upon exogenous lactate in neuronal cells, accompanied by increased mitochondria fission. Again, C646 reverses mitochondria dysfunction and fission.Conclusions:Our results shed light on how CRS intensifies the ischemic damage post-stroke. Central mechanism is histone lactylation which triggers neuronal mitochondria fission, thereby impacting the outcomes related to stress-associated stroke. Lactylation antagonists offer promising avenues for therapeutic interventions, mitigating the adverse effects of stress on stroke outcomes.

Stroke, Volume 55, Issue Suppl_1, Page AWP142-AWP142, February 1, 2024. Background:Intracranial atherosclerotic disease (ICAD) is associated with high recurrence rates of stroke despite aggressive medical management. Low wall shear stress (WSS) alters endothelial function and changes in WSS within the post-stenotic region of ICAD lesions is a potential driver of stroke recurrence.Methods:Using the SAMMPRIS imaging dataset, we identified medically managed patients with symptomatic middle cerebral artery (MCA) stenosis measured by CTA. WSS was calculated by creating a 3D volumetric mesh from CTA source imaging. Pulsatile flow profile reference standard boundary conditions were applied at pressure outlets to simulate normal hemodynamics. Arterial segments extending from the stenosis to the MCA bifurcation were captured and quantified. Contralateral arterial segments were matched by length and area. The ratio of area with low WSS (

Stroke, Volume 55, Issue Suppl_1, Page A18-A18, February 1, 2024. Background:Exposure to ambient air pollution causes neuroinflammation and white matter (WM) damage. In patients with preexisting cerebrovascular disease, pollution exposure can compound underlying pathology and may accelerate functional decline. Major mechanisms of this toxicity are microglial reactivity and oxidative stress. We therefore hypothesized that attenuation of the Toll-like receptor 4 (TLR4)-dependent microglial response would significantly decrease oxidative WM damage in a joint experimental model of pollutant exposure and chronic cerebral hypoperfusion modeled by surgical bilateral carotid artery stenosis (BCAS).Methods:Inducible microglial/macrophage-specific TLR4 deletion was achieved using a Tamoxifen-induced Cx3cr1CreER+/- mouse model. Male and female Cx3cr1CreER+/- mice treated with tamoxifen (i-mTLR4-ko) or corn oil (control) were exposed to 120 hours of filtered air (FA) or aerosolized diesel exhaust particulate (DEP), and 30 days of BCAS or sham surgery using a factorial design. The 8 experimental groups were: 1) control/FA (n=10), 2) control/DEP (n=10), 3) control/FA + BCAS (n=9), 4) control/DEP+BCAS (n=10), 5) i-mTLR4-ko/FA (n=9), 6) i-mTLR4-ko/DEP (n=8), 7) i-mTLR4-ko/FA + BCAS (n=8), and 8) i-mTLR4-ko/DEP+BCAS (n=10). Immunofluorescence was used to identify 4-HNE and 8-OHdG expression in the corpus callosum (CC).Results:While control mice showed elevations of 4-HNE in the CC after DEP (p

Stroke, Volume 55, Issue Suppl_1, Page ATP316-ATP316, February 1, 2024. Introduction:Tamoxifen (TAM), a selective estrogen receptor modulator, is a first-line treatment to prevent recurrence of hormone receptor positive breast cancer. Stroke risk is increased in women with low estrogen and doubles in women after the age of 55 (average age of menopause). Critically, women taking TAM as breast cancer therapy had increased risk of ischemic stroke (82%). We hypothesize treatment with TAM will increase stroke severity, which is associated with increased blood brain barrier (BBB) damage and worsened neuroinflammation. We investigated effects of TAM on mitochondrial stress and cellular function in astrocytes and microglia, key cells of the BBB and neuroimmune response, respectively.Methods:Cultured female human astrocytes and HMC3 microglia were treated with TAM (1uM), 17ß-estradiol (10nM, E2), 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. Mitochondrial function was assessed using a Seahorse XFe96 Analyzer. Microglial expression of mitochondrial proteins (Complex I & III and DRP1) was analyzed with western blot, and function was assessed with flow cytometry afterin vitrophagocytosis of pHrodo red zymosan.Results:TAM reduced maximal (p =0.0174) and basal respiration (p =0.0149) under OGD conditions in microglia compared with DMSO or E2 treatment. However, in astrocytes, maximal and basal respiration were increased in OGD (p =0.0003, p =0.0002). There was no significant difference in expression of mitochondrial proteins or phagocytic function in HMC3 microglia under either normoxic or OGD conditions after TAM treatment.Conclusions:TAM treatment resulted in a cell type-specific alteration in mitochondrial stress response. Since mitochondrial stress is a hallmark of stroke pathophysiology, and microglia and astrocytes are among the earliest cells to respond to ischemia, treatment with tamoxifen might alter the cellular environment, by its divergent actions on these two cell types, leading to worsened stroke outcomes. These data support the need forin vivoinvestigation to elucidate the mechanism by which TAM is altering cellular response. Support: RFAG042189 to FS, 1F30NS131053 to MEZ

Stroke, Volume 55, Issue Suppl_1, Page ATMP114-ATMP114, February 1, 2024. Introduction:Iron is an essential element for vascular wall maintenance. However, iron deposition in the vascular wall may cause oxidative stress, which can attack DNA, proteins, and lipid membranes via the Fenton/Haber-Weiss reaction. Iron-induced oxidative stress triggers lipid oxidation, inflammation, endothelial cell activation and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture.Methods:Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet or a normal diet. Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination.Results:The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%;p< 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2′-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p< 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2′-deoxyguanosine in both normal diet and iron-restricted diet mice aneurysms.Conclusions:Compared with a normal diet, an iron-restricted diet reduced the incidence of intracranial aneurysmal rupture in mice via inhibition of iron accumulation in the aneurysmal wall. Iron may be a potential therapeutic target to prevent intracranial aneurysm rupture. Long-term iron restriction may be required to affect aneurysm formationrupture.

Stroke, Volume 55, Issue Suppl_1, Page ATMP12-ATMP12, February 1, 2024. Background:Large-vessel vasculopathy (LVV), such as moyamoya syndrome, increases stroke risk with sickle cell disease (SCD). We hypothesized that tissue-based cerebral blood flow (CBF) and oxygen extraction fraction (OEF), as indicators of hemodynamic and metabolic stress, would differ in hemispheres with vs. without LVV.Methods:Patients underwent serial brain MRI and time-of-flight MRA to quantify voxel-wise CBF, OEF, and infarcts. LVV was defined as 75-99% stenosis of a major anterior circulation artery. Hemispheres with large vessel occlusion or revascularization surgery were excluded. Infarcted voxels were removed. Mean hemispheric (hemi-) CBF, OEF of the anterior circulation were extracted based on a vascular territory template. Hemi- OEF was normalized to whole brain OEF (nOEF). Hemi- cerebral metabolic rate of oxygen utilization (CMRO2) was calculated from arterial oxygen content, hemi- CBF, and hemi- OEF. Mann-WhitneyUwas used to compare hemispheres with vs. without LVV. Effects of age, hemoglobin, and repeated MRIs were adjusted for in linear mixed model.Results:Of 158 patients, 221 MRI and MRAs were performed. At baseline, LVV occurred in 5% of hemispheres. Median infarct volume was larger in hemispheres with vs. without LVV (6.5 vs. 0.04 mL,p

Stroke, Volume 55, Issue Suppl_1, Page AWP289-AWP289, February 1, 2024. Introduction:Blunted night-to-day blood pressure (BP) dipping was common in ischemic cerebrovascular disease (ICVD). BP dipping could be influenced by baroreflex, which stabilized BP by regulating sympathovagal balance. We sought to determine the relationship between baroreflex function and BP dipping in patients with ICVD.Methods:Patients with ICVD stable for at least 3 days were enrolled. Beat-to-beat BP and ECG were monitored in 3 phases of active standing [supine (S), supine to upright (SU), upright (U), 4 min each]. Baroreflex function was evaluated by time-domain and frequency-domain baroreflex sensitivity (BRS) and by indices of sympathovagal balance [low (0.04-0.15 Hz) to high (0.15-0.4 Hz) frequency ratio (LHR) of systolic BP (SBP) and RR interval (RRI)]. BP dipping was measured as percentage with 24h ambulatory BP monitoring. SBP dipping

Stroke, Volume 55, Issue Suppl_1, Page A29-A29, February 1, 2024. Background:While Nitroglycerin (GTN) is predominantly recognized as a vasodilator for ischemic heart disease, its potential neuroprotective properties in acute ischemic stroke (AIS) remain under exploration. This investigation sought to discover the therapeutic advantages of GTN post-recanalization in AIS and underlying mechanisms.Methods:Adult male Sprague Dawley rats were categorized into sham, MCAO with or without GTN treatment, and MCAO treated with both GTN and KT5823, an inhibitor of cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG). AIS was induced by MCAO for 2 hours followed by 6 or 24 hours of reperfusion (tMCAO). A 28-hour MCAO without reperfusion was defined as the permanent MCAO group (pMCAO). The study assessed infarct volumes, neurological impairments, glucose metabolism metrics (lactate and ROS levels), nitric oxide (NO) and cGMP levels (via ELISA). mRNA and protein expressions of hyperglycolysis (GLUT1, GLUT3, PFK, LDH), gluconeogenesis (PCK1, PCK2), ER stress (BIP, PERK, EIF2α, ATF4, CHOP) as well as signaling molecules (PKG, AMPK), were measured with RT-PCR and Western blotting. Apoptotic cell death was evaluated using TUNEL.Results:GTN significantly reduced cerebral infarct volumes, neurological deficits, apoptotic cell death, lactate and ROS levels and decreased the expression of NO and cGMP levels and key glucose metabolism and ER stress-related genes and proteins, including GLUT1, GLUT3, PFK1, LDH, PCK1, PCK2, BIP, PERK, EIF2α, ATF4, CHOP and phosphorylated AMPK, while boosting PKG expression only in tMCAO. The coadministration of GTN and KT5823 reversed the observed GTN benefits.Conclusion:Our findings illuminate that GTN showcases neuroprotective properties in tMCAO (but not pMCAO) by enhancing glucose metabolism (hyperglycolysis and gluconeogenesis), controlling ER stress, and working through the NO-CGMP-PKG signaling cascade to inhibit AMPK phosphorylation.

Stroke, Volume 55, Issue Suppl_1, Page AWP35-AWP35, February 1, 2024. Introduction:A life-threatening medical event such as stroke can trigger symptoms of post-traumatic stress disorder (PTSD). Less is known about the risk of PTSD among individuals who present with stroke-like symptoms but are ultimately diagnosed with a stroke mimic.Aim:To examine the association between final diagnosis of stroke mimic, stroke, or TIA and risk of developing PTSD 1 month after the index event.Methods:We enrolled patients with suspected stroke or TIA from an urban academic medical center. The PTSD Checklist 5 for DSM-5 (PCL-5) was administered at enrollment to assess pre-existing PTSD, and at 1-month after discharge to assess PTSD related to the index event. The index event was adjudicated via chart review as a stroke, TIA, stroke mimic, or equivocal by a neurologist blinded to PTSD status. Logistic regression was used to determine odds of developing clinically significant PTSD (PCL-5 &ge 33) for stroke mimics compared to stroke or TIA at 1 month after adjusting for age, gender, ethnicity, initial NIH Stroke Scale, discharge modified Rankin Score, and prior PTSD. Multiple imputation was used to account for missingness in data. Equivocal cases were excluded.Results:In our sample of suspected stroke (n= 1,000, 51% female, age = 62 ± 15 y), 596 (59.6%) had a stroke, 79 (7.9%) had a TIA, 274 (27.4%) had a stroke mimic, and 51 (5.1%) were equivocal or missing. PTSD prevalence numbers (rates) at 1 month for stroke mimic, stroke, and TIA, respectively, were 30 (15.1%), 27 (6.3%), and 3 (5.5%). In the fully adjusted model, the odds of 1-month PTSD were higher for stroke mimics vs. patients with stroke, OR = 2.99, 95% CI [1.45, 6.18],p< .01, but not for stroke mimics vs. TIA, OR = 1.67,p= .45. Pre-existing PTSD was associated with increased odds of 1-month PTSD, OR = 10.32, 95% CI [5.30, 20.10],p< .01. No other covariates were associated with PTSD.Conclusion:Experiencing a stroke mimic compared to a stroke was associated with increased risk of having PTSD 1 month after the event. Clinicians should consider the risk of psychological distress particularly among individuals presenting with sudden stroke-like symptoms diagnosed as stroke mimics.

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Group 3 innate lymphoid cells (ILC3s) recently emerged as important regulators and potential drug targets for IBD. However, the response of ILC3s to environmental stimuli during intestinal inflammation remains elusive. IRE1a-XBP1 serves as the regulatory hub of the endoplasmic reticulum stress response that plays a vital role in intestinal inflammation.

Objectives
This study aimed to examine the prevalence of post-traumatic stress disorder (PTSD) in victims-survivors of intimate partner violence (IPV) consulting at the specialised and original facility ‘Maison des Femmes’ (MdF) or in two close municipal health centres (MHCs).

Design
A mixed-methods study using a convergent parallel design from July 2020 to June 2021.

Setting/participants
A questionnaire was proposed to women aged 18 years and over having suffered from IPV, in the MdF and in two MHCs. We also conducted qualitative interviews with a subsample of the women, asking for victim-survivors’ perceptions of the effect of the MdF’s care.

Primary and secondary outcome measures
The presence of a PTSD using the PTSD self-report checklist of symptoms, possibility of reaching women by phone 6 months after the inclusion visit, level of self-rated global health, number of emergency visits in the past 6 months, substances use, readiness to change and safety behaviours.

Results
A total of 67 women (mean age: 34 years (SD=9.7)) responded to our questionnaire. PTSD diagnosis was retained for 40 women (59.7%). Around 30% of participants self-rated their global health as bad. Less than 30% (n=18) of women were regular smokers, and only 7.5% of participants had a problematic alcohol use (Alcohol Use Disorders Identification Test-Consumption score ≥4), 19.4% women used psychotropic drugs. Six months after inclusion, half of participants had been reached by phone. Analysis of the qualitative interviews clarified victim-survivors’ perceptions of the MdF’s specific care: social networking, multidisciplinary approach, specialised listening, healthcare facilities, evasion and ‘feeling at home’.

Conclusions
The high prevalence of PTSD at inclusion was nearly the same between the three centres. This mixed-methods comparison will serve as a pilot study for a larger comparative trial to assess the long-term impact of the MdF’s specialised care on victims-survivors’ mental health, compared with the care of uncoordinated structures.

Trial registration number
NCT04304469.

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