Artery Occlusion Research Articles

Physical Exercise Improves the Neuronal Function in Ischemic Stroke Via Microglial CB2R/P2Y12 Signaling.

Physical exercise (PE) may be the single most important and accessible lifestyle habit throughout life, it inhibits the neuroinflammatory response and protects the brain against damage. As the innate cells in brain, microglia undergo morphological and functional changes to communicate with neurons protecting the neurons from injury. Herein, aiming at exploring the effects of PE on the communication between microglia-neuron during acute ischemic cerebral infarction, we carried out running wheel training before the conduction of transient middle cerebral artery occlusion (tMCAO) in C57BL/6J and Cx3cr1-GFP mice. We found that microglial P2Y12 expression in the peri-infarct area was decreased, microglial dynamics and microglia-neuron communications were impaired, using in vivo two-photon imaging. PE up-regulated the microglial P2Y12 expression, increased the microglial dynamics, and promoted the contacts of microglia with neurons. As a result, PE inhibited neuronal Ca2+ overloads and protected against damage of the neuronal mitochondria in acute tMCAO. Mechanistically, PE increased the cannabinoid receptor 2 (CB2R) in microglia, promoted the phosphorylation of Nrf2 (NF-E2-related factor 2) at ser-344, increased the transcription factor level of Mafk, and up-regulated the level of P2Y12, whereby PE increased the levels of CB2R to promote microglia-neuron contacts to monitor and protect neuronal function.

Spontaneous Non-Aneurysmal Convexity Subarachnoid Hemorrhage: A Scoping Review of Different Etiologies beyond Cerebral Amyloid Angiopathy.

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient's age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.

Glucose-Stimulated Mucus Secretion by Goblet Cells Mitigates Intestinal Barrier Dysfunction in a Rat Model of Mesenteric Ischemia/Reperfusion Injury

BackgroundSuperior mesenteric ischemia/reperfusion (I/R) causes barrier dysfunction and facilitates bacterial translocation (BT) in the small intestine, which can even lead to systemic sepsis. Our previous research showed that luminal administration of glucose and its anaerobic glycolytic metabolites exerted cytoprotective effects on epithelial cells and ameliorated I/R-induced BT in the liver and spleen. Notably, the reduction of BT occurs over the whole intestinal tract, not only restricted in the ligated glucose-containing loop. ObjectivesIn this study, we hypothesized that local jejunal glucose-contacting might confer on the remote intestinal epithelium regeneration potential, fortify their barrier function and goblet cell secretory activity. MethodsTwo 10-cm jejunal segments were isolated in Wistar rats. One segment was ligatured at both ends and infused with Krebs buffer containing 0- or 50-mM glucose (local loop), whereas the adjacent segment was left unaltered and not exposed to glucose (remote loop). The rats then underwent either a sham operation or I/R challenge by occlusion of the superior mesenteric artery for 20 min, followed by reperfusion for 1 h. ResultsEnteral addition of glucose in the local jejunum loop alleviated ischemia-induced barrier defects, histopathological scores, cell death, and mucosal inflammation (myeloperoxidase and inflammatory cytokine production) in the remote jejunum. After ischemia, goblet cells in the remote jejunum showed cavitation of mucin granules and low MUC2 expression. Local addition of glucose enhanced MUC2 synthesis and stimulated a jet-like mucus secretion in the remote jejunum, which was accompanied by the restoration of crypt activity. ConclusionsOur results showed local enteral glucose effectively mitigates I/R-induced barrier dysfunction, suggesting that local glucose-stimulated mucus secretion by remote goblet cells may serve to mitigate mucosal inflammation and BT. We provide a more precise barrier protection role of enteral glucose upon I/R challenge, presenting new opportunities for future therapeutic potential.

ATP-sensitive potassium channel opener, Nicorandil, inhibits NF-κB/AIM2/GSDMD pathway activation to protect against neuroinflammation in ischemic stroke

The absent in melanoma 2 (AIM2) inflammasome contributes to ischemic brain injury by inducing cell pyroptosis and inflammatory responses. Our research group has previously demonstrated that ATP-sensitive potassium channels (KATP channels) openers can modulate neuronal synaptic plasticity post-ischemic stroke for neuroprotection. However, the specific mechanisms of KATP channels in the inflammatory response following ischemic stroke remain unclear. Here, we assessed cellular damage by observing changes in BV-2 morphology and viability. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, mNSS scoring, Nissl staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to evaluate behavioral deficits, brain injury severity, and neuronal damage in mice subjected to middle cerebral artery occlusion (MCAO). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to measure cell pyroptosis and nuclear factor-kappaB (NF-κB) activation in vivo and in vitro. We observed that AIM2 protein expression was upregulated and localized within the cytoplasm of BV-2 cells. Notably, low-dose Nicorandil treatment reduced inflammatory cytokine secretion and pyroptosis-related protein expression, including AIM2, cleaved cysteinyl aspartate-specific protease-1 (cleaved caspase-1), and Gasdermin D N-terminal (GSDMD-NT). Further investigations revealed that the KATP channel inhibitor 5-HD upregulated p-NF-κB p65, NF-κB p65, and p-IκBα expression, reversing Nicorandil's neuroprotective effect in vivo. In summary, our results suggest that Nicorandil may serve as a potential therapeutic option for ischemic stroke. Targeting AIM2 and NF-κB represents effective strategies for inhibiting neuroinflammation.

LINC00894 Regulates Cerebral Ischemia/Reperfusion Injury by Stabilizing EIF5 and Facilitating ATF4-Mediated Induction of FGF21 and ACOD1 Expression

The non-coding RNA LINC00894 modulates tumor proliferation and drug resistance. However, its role in brain is still unclear. Using RNA-pull down combined with mass spectrometry and RNA binding protein immunoprecipitation, EIF5 was identified to interact with LINC00894. Furthermore, LINC00894 knockdown decreased EIF5 protein expression, whereas LINC00894 overexpression increased EIF5 protein expression in SH-SY5Y and BE(2)-M17 (M17) neuroblastoma cells. Additionally, LINC00894 affected the ubiquitination modification of EIF5. Adeno-associated virus (AAV) mediated LINC00894 overexpression in the brain inhibited the expression of activated Caspase-3, while increased EIF5 protein level in rats and mice subjected to transient middle cerebral artery occlusion reperfusion (MCAO/R). Meanwhile, LINC00894 knockdown increased the number of apoptotic cells and expression of activated Caspase-3, and its overexpression decreased them in the oxygen–glucose deprivation and reoxygenation (OGD/R) in vitro models. Further, LINC00894 was revealed to regulated ATF4 protein expression in condition of OGD/R and normoxia. LINC00894 knockdown also decreased the expression of glutamate-cysteine ligase catalytic subunit (GCLC) and ATF4, downregulated glutathione (GSH), and the ratio of GSH to oxidized GSH (GSH: GSSG) in vitro. By using RNA-seq combined with qRT-PCR and immunoblot, we identified that fibroblast growth factor 21 (FGF21) and aconitate decarboxylase 1 (ACOD1), as the ATF4 target genes were regulated by LINC00894 in the MCAO/R model. Finally, we revealed that ATF4 transcriptionally regulated FGF21 and ACOD1 expression; ectopic overexpression of FGF21 or ACOD1 in LINC00894 knockdown cells decreased activated Caspase-3 expression in the OGD/R model. Our results demonstrated that LINC00894 regulated cerebral ischemia injury by stabilizing EIF5 and facilitating EIF5-ATF4-dependent induction of FGF21 and ACOD1.

Acute occlusion of the left main coronary artery following impedance rise after high‐frequency catheter ablation

Acute occlusion of the left main coronary artery following impedance rise after high‐frequency catheter ablation

Genistein-3′-sodium sulfonate promotes brain functional rehabilitation in ischemic stroke rats by regulating astrocytes polarization through NF-κB signaling pathway

The activation and polarization of astrocytes are involved in neuroinflammation and brain functional rehabilitation after ischemic stroke. Our previous studies display the neuroprotective effect of genistein-3′-sodium sulfonate (GSS) in the acute phase of cerebral ischemia-reperfusion injury (CI/RI). This study aimed to investigate the brain function improvement of GSS during the recovery period after CI/RI in rats and to explore the potential mechanism from the perspective of astrocyte activation and polarization. The transient middle cerebral artery occlusion (tMCAO) rats were treated with GSS (1 mg/kg) continuously for 28 days. The behavior tests were measured to assess neurological function. The mRNA and protein expression in affected cerebral cortex were detected on day 29 after tMCAO. Our results demonstrated that GSS treatment significantly improved the spatial and temporal gait parameters in the Catwalk gait test, prolonged the time on the stick and increased the rotation speed in the rotarod test, and decreased the time to find the hidden platform and increased the time in the target quadrant in the Morris water maze test. In addition, GFAP, GBP2, C3, IL-1β protein expressions and Nos2A mRNA level were decreased, while Nrf2, BDNF, IL-10 protein expressions and Sphk1 and Nef2l2 mRNA levels increased after GSS treatment. Interestingly, GSS presented a strong binding affinity to TLR4 and suppressed the activation of NF-κB signaling. In conclusion, GSS can promote brain function recovery by inhibiting astrocyte activation and polarization to A1 phenotype, and enhancing astrocyte polarization to A2 phenotype via inactivating TLR4/NF-κB signaling, which provide a candidate compound for clinical rehabilitation therapy in the recovery period after ischemic stroke.

Pericyte response to ischemic stroke precedes endothelial cell death and blood-brain barrier breakdown.

Stroke is one of the leading causes of death and disability, yet the cellular response to the ischemic insult is poorly understood limiting therapeutic options. Brain pericytes are crucial for maintaining blood-brain barrier (BBB) integrity and are known to be one of the first responders to ischemic stroke. The exact timeline of cellular events after stroke, however, remains elusive. Using the permanent middle cerebral artery occlusion stroke model, we established a detailed timeline of microvascular events after experimental stroke. Our results show that pericytes respond already within 1 hour after the ischemic insult. We find that approximately 30% of the pericyte population dies as early as 1 hour after stroke, while ca 50% express markers that indicate activation. A decrease of endothelial tight junctions, signs of endothelial cell death and reduction in blood vessel length are only detected at time points after the initial pericyte response. Consistently, markers of BBB leakage are observed several hours after pericyte cell death and/or vascular detachment. Our results suggest that the pericyte response to stroke occurs early and precedes both the endothelial response and the BBB breakdown. This highlights pericytes as an important target cell type to develop new diagnostic and therapeutic tools.

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Design and Interrater Reliability of the Pediatric Version of the Race Scale: PedRACE.

Acute ischemic stroke is a leading cause of pediatric death and disability. A clinical scale adapted for children can ensure early detection of candidates for urgent acute ischemic stroke treatment. The Rapid Arterial Occlusion Evaluation (RACE) scale for adults, which scores 5 items (facial palsy 0-2; arm motor function 0-2; leg motor function 0-2; head/gaze deviation 0-1; and aphasia or agnosia 0-2), has good sensitivity and specificity in detecting large vessel occlusion. We adapted the previously validated RACE scale for use in children as the Pediatric RACE scale. This adapted scale was tested by prehospital/emergency room staff attending to patients covered by the Catalan Pediatric Stroke Code and child neurologists for its correlation with the Pediatric National Institutes of Health Stroke Scale and for interrater reliability. The study included 50 children, 18 with confirmed strokes (7 acute ischemic strokes and 11 hemorrhagic strokes). Prehospital/emergency staff and child neurologists agreed fully regarding 82% of patients and 100% regarding head/gaze deviation and agnosia. The Pediatric RACE scale correlated strongly with the Pediatric National Institutes of Health Stroke Scale in evaluations by child neurologists (Spearman ρ, 0.852; P<0.001) and prehospital/emergency staff (Spearman ρ, 0.781; P<0.001). The median Pediatric RACE score was significantly higher in patients with large vessel occlusion (6.5; interquartile range, 6-7) than with other etiologies. Pediatric RACE, showing good interrater reliability and correlation with the Pediatric National Institutes of Health Stroke Scale, is a simple scale to detect candidates for pediatric acute stroke treatment, designed for both prehospital and in-hospital use by non-neurologist medical staff.

Ginsenoside Rb1 reduced ischemic stroke-induced apoptosis through endoplasmic reticulum stress-associated IRE1/TRAF2/JNK pathway.

The neuroprotective function of ginsenoside Rb1 (GRb1) in cerebral ischemia-reperfusion (I/R) was lately emphasized. However, whether GRb1 plays a regulatory role on endoplasmic reticulum (ER) stress-associated pathway in cerebral I/R damage is still unclear. The aim of this study is to explore the function of GRb1 in cerebral ischemia-induced ER stress and the underlying mechanism related to IRE1/TRAF2/JNK pathway. Longa method, cerebral infarct volume, and HE staining were used to evaluate the efficacy of GRb1 in mice with a mouse model of middle cerebral artery occlusion reperfusion (MCAO/R). We also investigated the effect and mechanism of GRb1 against ischemic stroke using in vitro oxygen-glucose deprivation reperfusion (OGD/R) model. We found that GRb1 could improve neurological scores, infarct volume, and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis and ER stress, and this effect was attenuated by GRb1. In addition, GRb1 significantly reduced I/R-induced IRE1-TRAF2 interaction, IRE1, and JNK phosphorylation. The present study also confirmed that GRb1 significantly improved OGD/R-induced PC12 cells injury. GRb1 could decrease ER stress in OGD/R-injured PC12 cells, which was reflected by the decreased expression of GRP78 and CHOP. The ER stress inducer tunicamycin partially prevented the effects of GRb1 on cell viability, ER stress, and apoptosis after OGD/R, whereas the ER stress inhibitor 4-PBA exerted the opposite effect. Moreover, GRb1 markedly decreased IRE1-TRAF2 interaction, IRE1, and JNK phosphorylation in the presence of OGD/R insult. Furthermore, JNK inhibitor SP600125 and IRE1 inhibitor DBSA pretreatment further promoted the inhibition of GRb1 on ER stress induction and cell damage induced by OGD/R. Molecular docking further elucidated that the mechanism by which GRb1 improves cerebral ischemia maybe related to its direct binding to the kinase domain of IRE1, which in turn inhibited the phosphorylation of IRE1. Collectively, these results demonstrated that GRb1 reduced ischemic stroke-induced apoptosis through the ER stress-associated IRE1/TRAF2/JNK pathway and GRb1 has the potential as a protective drug for the treatment of cerebral ischemia.

Ultrasound-Assisted Sagittal View for Retrograde Puncture of the P2 Segment of Popliteal Artery for Recanalization of Femoropopliteal Lesions

To assess the safety and efficacy of ultrasound-assisted sagittal view for retrograde puncture of the P2 segment of popliteal artery (PA) for treating femoropopliteal lesions. A retrospective study was conducted on consecutive patients who underwent retrograde puncture of the PA for the recanalization of femoropopliteal lesions. A retrograde access was made to either the P2 or P3 segment of the PA in 23 cases. In 10 cases (8 men; mean age 68±9years), ultrasound-guided retrograde PA (P2 segment) puncture using the long-axis in-the-plane approach was performed, and in 13 cases (11 men; mean age 69±5years), angiography-guided retrograde PA (P3 segment) puncture was performed. Clinical data was compared preintraoperatively and postoperatively in the 2 groups. All occluded lesions were successfully recanalized via dual channel intervention. Puncture success were 100% (10/10) in the P2 group compared with 92.3% (12/13) in the P3 group (P>0.05). The mean puncture time in the P2 group was significantly shorter when compared to the P3 group (4.70±0.95mins vs 11.33±6.37mins; P<0.05). There was no difference in mean hemostasis time between the 2 groups (6.11±2.20mins vs 8.46±3.76mins; P>0.05). There were no in-hospital deaths in all patients. The occurrence of puncture-related complications in the P2 group was 10% compared with 15% in the P3 group (P>0.05). A low-flow arteriovenous fistula was observed in one case in the P3 group. None of the patients reported any access-related complication at a mean follow-up of 11.3±5.5months. Ultrasound-assisted sagittal view for retrograde puncture of the P2 segment of PA is at least as safe as angiography-guided retrograde puncture of the P3 segment for femoropopliteal lesions. Furthermore, this technique appears to be more suitable for patients with tandem iliofemoral artery occlusion, as it allows for the creation of a retrograde access.

Evaluation of early results of diagnosis and treatment of popliteal artery injury in knee trauma at Binh Dan Hospital

Objectives:To describe the clinical and subclinical signs for early diagnosis and evaluate the short-term outcomes of surgical treatment of popliteal artery injury in knee trauma. Materials and methods: A retrospective descriptive study was conducted on 30 patients with knee trauma and popliteal artery injury who underwent surgery at Binh Dan Hospital from August 2016 to June 2021. Results: The mean age of admitted patients was 35.5±12.8 years, predominantly male (73.3%). The majority of cases were due to traffic accidents (83.4%). Peripheral pulse was absent or decreased in 76.7% of patients. Most patients (95.3%) showed loss of flow signal on ultrasound. The most common surgical intervention was venous graft repair (63.3%). After surgery, 93.3% of patients had good flow restoration. The postoperative arterial occlusion rate was 6.7%. There were two cases that required a second surgery for popliteal artery recanalisation: one case where limb salvage was achieved, and one case that resulted in amputation. Conclusion: The application of appropriate diagnostic measures, emergency management, and surgical intervention has resulted in positive treatment outcomes, helping to reduce the rate of limb amputation and other severe complications

Strategies and outcomes of endovascular treatment of posterior inferior cerebellar artery aneurysms: a single center experience.

To explore safe and reliable strategies and outcomes of endovascular procedures in the treatment of posterior inferior cerebellar artery (PICA) aneurysms. Retrospectively reviewed and analyzed the cases of PICA aneurysms that undergone endovascular therapy from July 2017 through January 2022 in our neurosurgical center, as well as outcomes of long-term follow-up. Total 24 cases were enrolled. Majority of the PICA aneurysms (87.5%, 21/24) presented initially with subarachnoid hemorrhage (SAH) and only 3 cases were not ruptured when they were clinically diagnosed as PICA aneurysms. The patients were endovascularly given either aneurysm occlusion with selective coils (12 cases), embolization of aneurysms and parent arteries (7 cases: 3 cases with coils and 4 cases with Onyx liquid embolic agent), or stent-assisted coiling of the aneurysms (5 cases). One patient, who had comorbidity of intracranial hemorrhage and severe cerebral vasospasm, declined further post-surgery therapy, and discharged from the hospital with anticipation of poor outcome. The rest 23 patients were followed up for 3-24 months with a recurrence rate of 17.4% (4/23). Endovascular procedure of embolizing PICA aneurysms with selective coils or stent-assisted coils is feasible, safe, and reliable. Simplified embolization of the aneurysms or occlusion of the parent artery is recommended as the first choice for the ruptured and bleeding PICA aneurysms.

Prevalence and Predictors of Occlusive Myocardial Infarction in Patients Presenting With Non-ST-Elevation Acute Coronary Syndrome in Duhok, Iraq: A Cross-Sectional Study.

Background and aim Myocardial infarction is a major global health issue and the leading cause of death. Non-ST segment elevation acute coronary syndrome (NSTE-ACS) could behave like ST-segment elevation ACS in terms of causing total or near total occlusion of the coronary artery and leading to occlusive myocardial infarction (OMI). This study aims to assess OMI prevalence and associated factors in NSTE-ACS patients in Duhok, Iraq, to improve diagnosis and treatment outcomes. Materials and methods This prospective cross-sectional study, conducted at Azadi Heart Center and Zakho Teaching Hospital from March 2023 to March 2024, included 189 NSTE-ACS patients undergoing coronary angiography. Data collection encompassed demographics, clinical profiles, electrocardiographic (ECG) patterns, cardiac biomarkers, and angiographic outcomes. Patients were categorized into those with and without occlusive myocardial infarction (OMI). Results A total of 189 NSTE-ACS patients with a mean age of 58.65 (±10.38 SD) years were enrolled in the study. The overall OMI rate was 29.63%. OMI patients were older and had a higher prevalence of hypertension, dyslipidemia, and a family history of ischemic heart disease (IHD). Significant ECG changes associated with OMI included biphasic T-wave inversion and ST depression in specific leads. Marked elevation in troponin levels was also noted in OMI patients. The left anterior descending (LAD) artery was the most common culprit artery. Conclusions About one-quarter of our study cohort exhibited OMI. The condition was linked to clinical, ECG, and elevated troponin levels. The study underscores the importance of promptly recognizing occlusive myocardial infarction (OMI) in NSTE-ACS patients for better outcomes. Regular audits are imperative to augment awareness among healthcare professionals at cardiac centers regarding updated protocols and guidelines.

Blunt Traumatic Vertebral Artery Injury After Cervical Fracture Dislocation: A Systematic Review of the Literature.

Certain high-energy blunt forces may produce unstable cervical fractures with or without dislocation. In rare cases where the superior facets are dislocated, however showing a significant increase within the last decade, these types of injuries may include vertebral artery entrapment at the involvement level leading to artery dissection or occlusion. This phenomenon is usually seen at the C4-C5 and C5-C6 levels of injury. A systematic review of the literature was performed by examining online databases such as PubMed - NCBI, Web of Science, Cochrane Library, Scopus, and Embase to identify relevant scientific articles. Keywords (MeSH terms) used in the search included cervical spine injuries, cervical spine dislocation, cerebrovascular injury, vertebral artery injury, vertebral artery injury management, and incidence of vertebral artery injury. Initially, 1516 studies were identified as a primary search for screening. After excluding papers that did not fulfill the inclusion criteria, 34 studies were included in this review. Vertebral artery injury consists of a severe complication that could compromise a surgical intervention since the patient's clinical image may be unrevealing at first. Early diagnosis and correct timing constitute the golden standard for adequate treatment. This systematic review aims to summarize the current evidence for the diagnosis, management, and treatment of blunt traumatic vertebral artery injuries.

Targeted Antioxidant Therapy Reduces Hyperglycemic Exacerbation of Myocardial Ischemia-Reperfusion

IntroductionAcute hyperglycemia (HG) enhances inflammatory and oxidative stress and exacerbates myocardial infarct size during ischemia-reperfusion injury by activating splenic leukocytes. Formyl peptide receptor 1 (FPR1) on leukocytes is activated by and mediates myocardial ischemia-reperfusion injury. We hypothesize that selective FPR1 antagonist cinnamoyl-F-(D)L-F-(D)L-F (CF) or potent reducing agent tris (2-carboxyethyl) phosphine hydrochloride (TCEP) could abrogate hyperglycemic infarct exacerbation, both alone and synergistically via a novel CF-TCEP compound that would target leukocytes for antioxidative effect. MethodsAcute HG was induced in wild type mice with an intraperitoneal dextrose injection followed by left coronary artery occlusion (30 min) and reperfusion (60 min). In treatment groups, CF (0.1 mg/kg or 1 mg/kg), TCEP (1 mg/kg or 20 mg/kg), or the CF-TCEP conjugate (0.1 mg/kg) was administered intravenously before reperfusion. The hearts were harvested to measure infarct size (IF). ResultsHG resulted in >50% increase in IF compared to euglycemic mice (52.1 ± 3.0 versus 34.0 ± 3.2%, P < 0.05). Neither CF nor TCEP independently exerted an infarct-sparing effect at lower doses (46.2 ± 2.1% or 50.9 ± 4.1%, P > 0.05 versus HG control) but at high doses, significantly attenuated IF exacerbation (23.2 ± 5.2% or 33.9 ± 3.6%, P < 0.05 versus HG control). However, the low-dose CF-TCEP conjugate significantly reduced IF (39.1 ± 1.7%, P < 0.05 versus HG control). IF was decreased to near euglycemic control levels (P > 0.05). ConclusionsThe CF-TECP conjugate synergistically attenuated HG infarct exacerbation at significantly lower respective doses of CF and TCEP. In addition to the intrinsic anti-inflammatory effect of blocking FPR1, CF is also a feasible tool for leukocyte-targeted therapy to treat IRI.

Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i.

Acute and chronic brain damage in type 2 diabetes mellitus (DM) determines the need to investigate the neuroprotective potential of glucose-lowering drugs. The purpose was to directly compare the neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with different duration of action and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetic rats with and without stroke. DM was modelled using high-fat diet and nicotinamide+streptozotocin protocol. The following groups (n = 15 each) were formed: DM without treatment, treatment with liraglutide, dulaglutide, canagliflozin as well as control group without DM and treatment. After 8 weeks, 10 rats from each group underwent middle cerebral artery occlusion. In the reperfusion period neurological deficit, neuroglial damage markers and brain necrosis were evaluated. Brain slices from the remaining 5 animals in each group were histologically examined for microglial activation and neuronal damage. Brain damage was similar in "DM" and "Control" (17.53 [14.23; 26.58] and 15.87 [13.40; 22.68] % of total brain volume, respectively). All study drugs diminished damage volume comparing with "DM" and "Control" whereas the necrosis volume in "DM+Liraglutide" was smaller than in "DM+Canagliflozin" and did not significantly differ from "DM+Dulaglutide" (2.9 [1.83; 4.71], 6.17 [3.88; 8.88] and 4.57 [3.27; 7.90] %). The neurological deficit was more prominent in "DM" than in "Control", while all the drugs demonstrated similar positive effect. Neurofilament light chains (NLC) did not differ between "DM" and "Control". Dulaglutide and canagliflozin caused a marked decrease in NLC. Protein S100BB level was similar in "DM" and "Control". Liraglutide caused the largest S100BB decrease, while canagliflozin did not influence it. In chronic brain ischaemia, all drugs increased the number of normal neurons, but GLP-1RAs had a more pronounced effect. DM was accompanied by increased number of activated microglial cells in Cornu Ammonis (CA)1 hippocampal region. Both GLP-1RAs reduced the number of Iba-1-positive cells, with dulaglutide being more effective than liraglutide, whereas canagliflozin did not affect this parameter. GLP-1RAs and SGLT-2i have neuroprotective properties against acute and chronic brain damage in diabetic rats, although the infarct-limiting effect of GLP-1RAs may be more pronounced. GLP-1RAs and SGLT-2i exert their protective effects by directly influencing neuronal survival, whereas GLP-1RAs also affect microglia.

Clot patterns determined by DSA and CTA can help predict intracranial atherosclerotic stenosis in acute ischemic stroke patients.

This study examines whether clot patterns at large artery occlusion sites, as observed using digital subtraction angiography (DSA) and computed tomography angiography (CTA), can reliably indicate intracranial atherosclerotic stenosis (ICAS) in acute ischemic stroke (AIS) patients. We conducted a retrospective analysis of patients treated with stent retriever thrombectomy for intracranial occlusions at our institute since 2017, with follow-up assessments conducted at 3 months. The patients were grouped based on the initial angiography clot topographies (i.e., cut-off or tapered signs). We assessed the potential of these topographies in predicting ICAS, including a clinical outcome analysis based on clot pattern, age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and onset-to-door time. Among 131 patients (with a mean age of 66.6 years), the clot pattern emerged as a significant predictor of ICAS. The DSA-based model had a predictive area under the curve (AUC) of 0.745, with 55.1% sensitivity and 94.0% specificity. A multivariate model including age, onset-to-door time, TOAST classification as large artery atherosclerosis (LAA), and the presence of the tapered sign in clot patterns had an AUC of 0.916. In patients over 65 years of age with an onset-to-door time of >5 h and exhibiting a tapered sign in the clot pattern, the AUC reached 0.897. The predictive ability of the tapered sign was similar in DSA and CTA, showing 73.4% agreement between modalities. The clot pattern with the tapered sign as observed using DSA is significantly associated with ICAS. Incorporating this clot pattern with age, TOAST classification as LAA, and onset-to-door time enhances the prediction of ICAS. The clot pattern identified by CTA is also a reliable predictor, highlighting the importance of assessing clot patterns in ICAS identification.

Retrieval of n-Butyl Cyanoacrylate Cast Migrated to the Dorsalis Pedis and Posterior Tibial Artery During Embolization of the Deep Circumflex Iliac Artery Using the Stent Retriever Device: A Case Report.

This case highlights the innovative application of stent retriever devices for retrieving migrated NBCA casts, traditionally used for stroke management in peripheral arterial occlusions. This adaptation offers clinicians a new, effective tool for managing embolization complications, such as unintended material migration that can cause severe ischemia. Implementing this technique could change clinical practice by providing a reliable method to swiftly address and resolve potentially limb-threatening situations, thereby improving patient outcomes and procedural safety. This advancement in interventional radiology enhances clinicians' ability to handle complex embolic events with greater confidence and efficacy.