Search Results (569)

Objective: This study aimed to evaluate whether modifying the post-processing algorithm of Twin-Spiral Dual-Energy computed tomography (DECT) improves infarct detection compared to conventional Dual-Energy CT (DECT) and Single-Energy CT (SECT) following endovascular therapy (EVT) for large vessel occlusion (LVO). Methods: We retrospectively analyzed 52 patients who underwent Twin-Spiral DECT after endovascular stroke therapy. Ten patients were used to generate a device-specific parameter (“y”) using an AI-based neural network (SynthSR). This parameter was integrated into the post-processing algorithm for edema map generation. Quantitative Hounsfield unit (HU) measurements were used to assess density differences in ischemic brain tissue across conventional virtual non-contrast (VNC) images and edema maps. Results: The median HU of infarcted tissue in conventional mixed DECT was 33.73 ± 4.58, compared to 22.96 ± 3.81 in default VNC images. Edema maps with different smoothing filter settings showed values of 14.39 ± 4.96, 14.50 ± 3.75, and 15.05 ± 2.65, respectively. All edema maps demonstrated statistically significant HU differences of infarcted tissue compared to conventional VNC images ($p<0.001$) while maintaining the density values of non-infarcted brain tissue. Conclusions: Enhancing the post-processing algorithm of conventional virtual non-contrast imaging improves infarct detection compared to standard mixed or virtual non-contrast reconstructions in Dual-Energy CT. Full article

Background/Objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We aim to determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD. Methods: Composite of CVD [coronary heart disease, heart failure (HF)], its individual components, and AF were assessed. Multi-marker CSVD score was used to reflect increasing CSVD burden (cerebral microbleeds (CMBs), high-burden perivascular spaces, extensive white matter hyperintensity, cortical superficial siderosis, or covert brain infarcts were assigned 1 point each, with a range of 0–5). We related prevalent CVD, its individual components, and AF to multi-marker CSVD score and individual CSVD markers using logistic regression analyses adjusted for age, sex, FHS cohort, time between MRI and clinic exam (model-1), and vascular risk factors (model-2). Results: In 3413 participants (mean age: 59 ± 14 years, 53.4% women), 11% had prevalent CVD or AF, 8% had prevalent CVD, and 4% had prevalent AF. One CSVD marker was seen in 23% participants, and 9% had ≥ 2 markers. In multivariable-adjusted analyses, composite prevalent CVD and AF was associated with the presence of one CSVD marker (OR: 1.38, 95% confidence interval [CI]: 1.05–1.84). The association with ≥2 CSVD markers was not significant. Only CMBs were associated with components of CVD and AF, with the highest odds of association with HF. Conclusions: Prevalent CVD (including AF) is associated with the presence of CSVD, with all components associated with CMBs. Full article

Astrocyte activation and gender differences play critical roles in the prognosis following stroke. Recent studies have shown that optogenetic technology can promote brain repair after stroke by activating astrocytes in male rats. However, it remains unclear whether gender differences influence the efficacy of optogenetic activation of astrocytes in regulating post-stroke brain repair and its underlying mechanisms. In this study, we activated astrocytes in the ipsilateral cortex of adult glial fibrillary acidic protein-channelrhodopsin 2-enhanced yellow fluorescent protein (GFAP-ChR2-EYFP) transgenic Sprague Dawley rats using optogenetic stimulation at 24, 36, 48, and 60 h after inducing photothrombosis stroke. Neurobehavioral tests, cresyl violet staining, RT-qPCR, Western blot, and immunofluorescence analysis were performed on both female and male rats. Our results showed that male rats exhibited significant improvements in behavioral scores and reduction in infarct size after optogenetic activation of astrocytes at three days post-stroke (p < 0.05), whereas no significant changes were observed in female rats. Additionally, in female rats, the expression of basic fibroblast growth factor (bFGF) increased after ischemic stroke and astrocytic optogenetic stimulation (p < 0.05), leading to enhanced endothelial cell proliferation compared to male rats (p < 0.05). In vitro experiments further demonstrated that the astrocyte activation was inhibited in the presence of bFGF (p < 0.05). These findings suggest that the increase in bFGF levels in females following stroke may inhibit the optogenetic activation of astrocytes, thereby attenuating the therapeutic effect of astrocyte activation on post-stroke brain repair. This study provides important insights into the gender-specific roles of astrocytes in the acute phase of ischemic stroke. Full article

Background: Intercellular communication, facilitated by exosomes (Exos) derived from endothelial cells (ECs), significantly influences the regulation of angiogenesis. Leech extract significantly reduces ischemia–reperfusion injury, promotes angiogenesis, and improves neurological function in mice with stroke. However, further investigation is required to determine whether leech promotes angiogenesis through EC-Exo. Objective: This study aims to further explore whether leech regulates Exos to promote the establishment of collateral circulation in mice with ischemic stroke (IS) and the specific mechanisms involved. Methods: Here, we utilized an in vitro co-culture system comprising ECs and pericytes to investigate the impact of Leech-EC-Exo on enhancing the proliferation and migration of mouse brain microvascular pericytes (MBVPs). We further established an in vivo mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) to investigate the effects and underlying mechanisms of leech on collateral circulation establishment. Results: The findings demonstrated that leech significantly enhanced the in vitro cell migration number and migration number of pericytes. Therefore, it can also enhance the effect of EC-Exo on improving the infarct area and gait of mice, as well as modulating the HIFα-VEGF-DLL4-Notch1 signaling pathway to promote cerebral angiogenesis and facilitating the stable maturation of neovascularization in vivo. Conclusions: These results suggest that leech has the potential to enhance collateral circulation establishment, and its mechanism may involve the modulation of miRNA content in Exos and the promotion of signaling pathways associated with angiogenesis and vascular maturation. Full article

Stroke is still considered a predominant cause of morbidity and mortality, for which research on prevention and cure has been sought to prevent neuronal damage after a stroke incident. In this research, we evaluated the protective effects of virgin coconut oil (VCO) using behavioral, morphophysiological, and gene expression parameters using an ischemic stroke surgical rat model using Sprague Dawley (SD) rats. Eight-week-old SD rats were subjected to repeated oral administration (5 mL/kg/day) of either 1% Tween 80 or VCO. For behavioral and morphophysiological parameters, surgery was performed for each group, after which neurological scoring was performed at 4 h, 24 h, 48 h, 5 d, and 10 d. Further, hematological and brain morphology assessment was performed after euthanasia and necropsy of the animals. For gene expression studies, surgery was performed with animals sacrificed at different time points (baseline, before surgery, 4 h, 24 h, and 48 h after surgery) to collect the brain. Results of the study showed that there are differences in the neurological scores between the two treatments 24 h, 48 h, and 5 d after surgery. Brain morphology assessment also showed favorable results for VCO for infarct size, edema, and hypoxic neurons. Gene expression studies also showed positive results with an increase in the relative expression of angiogenin (Ang), angiopoietin (Angpt 1), Parkin, dynamin-related protein 1 (Drp 1), mitofusin 2 (Mfn 2), and mitochondrial rho (Miro) and decreased relative expression of caspase 3, receptor for advanced glycation end-product (Rage), and glyceraldehyde-3-phosphate dehydrogenase (Gapdh). In summary, the current study shows that VCO may have protective effects on the brain after stroke, which may be explained by the results of the gene expression studies. Full article

Reactive oxygen species (ROS) contribute to cerebral damage in transient cerebral ischemia, making their elimination a key therapeutic target. Osteogenic disorder Shionogi (ODS) rats, which lack endogenous L-ascorbic acid (AA) synthesis, serve as a useful model for investigating AA’s protective effects against ischemic brain injury. ODS rats were given an AA-free diet (0% AA), 0.1% AA, or 1% AA in drinking water for two weeks before undergoing middle cerebral artery occlusion and reperfusion (MCAO/Re). The 0% AA group exhibited pronounced damage following MCAO/Re, characterized by the induction of lipid peroxidation, O₂⁻ production, inflammation-related gene expression, and extensive infarct formation. In contrast, the 1% AA group showed reductions in these markers, along with fewer TUNEL-positive cells and a smaller infarct volume. Notably, sodium-dependent vitamin C transporter 2 (SVCT2) expression increased in both two AA-supplemented groups, although the 0.1% AA group did not exhibit sufficient improvement in post-ischemic damage. A two-week intake of AA significantly alleviated MCAO/Re-mediated injuries associated with oxidative stress and inflammation in ODS rats. Sufficient AA intake is thus supposed to mitigate ischemic damage, possibly through SVCT2 upregulation and enhanced AA availability, leading to the suppression of oxidative stress and inflammation. Full article

Fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM_2.5) has been extensively studied due to its adverse health effects. Most research has focused on its impact on the respiratory system; however, increasing attention is being directed toward its effects on the brain. Associations between air pollution and neurological disorders—such as Alzheimer’s disease, cerebral infarction, and autism spectrum disorder—have been reported, with mechanism-based studies in animal models providing further insights. PM_2.5 comprises a complex mixture of thousands of chemical constituents. To elucidate its neurotoxicity mechanisms, it is essential to investigate both its transport pathways to the brain and the specific actions of its individual components. This review highlights key PM_2.5 components—water-soluble ions, metals, carbonaceous particles, polycyclic aromatic hydrocarbons, quinones, plastics, and bioaerosols—and outlines their potential routes of entry into the central nervous system, along with their associated mechanisms of action. By integrating these findings, this review contributes to a deeper understanding of the neurological effects mediated by PM_2.5, which represent one of the most critical aspects of its health impact. Full article

Background and Clinical Significance: Pituitary apoplexy is an extremely rare condition in children and adolescents with a rapid onset due to acute hemorrhage, infarction, or both in the pituitary gland. Most frequently, pituitary apoplexy is an asymptomatic or subclinical entity. Few cases of pituitary apoplexy with concurrent SARS-CoV-2 infection or COVID-19 vaccination have been reported. Case Presentation: We present the case of a 13-year-8-month-old boy who presented in our pediatric endocrinology department for the evaluation of short stature. He was previously diagnosed with secondary hypothyroidism and was treated with levothyroxine. At admission, clinical examination revealed a height of 141 cm (−2.68 SD/−2.4 SD corrected for mid-parental height), normal weight (60th centile), Tanner-stage G2P1, and delayed bone age. Basal IGF1 was normal, but the tests performed to assess the GH reserve confirmed the GH deficiency (peak GH value 3.11 ng/mL after clonidine/0.95 ng/mL after insulin). The brain MRI revealed a subacute pituitary hemorrhage. Thrombophilia and coagulopathies were excluded by further testing. Anti-SARS-CoV-2 (anti-S-protein IgG) antibodies (>200 BAU/mL) were compatible with COVID-19 infection, indicating a possible association between these two entities. At 3-month follow-up, physical examination showed a 3 cm height gain and advancing pubertal development (G4P2). Newer MRI found changes consistent with resolving hemorrhage. The patient was provided immediately with recombinant human GH and aromatase inhibitor therapy to maximize GH treatment response. During follow-up, the rGH dose was adjusted based on IGF1 values, and after 3 years and 10 months, rGH treatment was stopped, reaching a height of 172.3 cm (−0.51 SD) and surpassing the initial prediction of 164.5 cm. Conclusions: Pituitary apoplexy, an even rarer complication in the pediatric population, may be associated with SARS-CoV-2 infection. Further studies are necessary to better understand the intertwining of those conditions. Full article

Background: Chronic ischemic stroke presents a significant challenge in neurology, with limited therapeutic options available for long-term recovery. During cerebral infarction, anti-inflammatory phenotype microglia/macrophages produce anti-inflammatory cytokines and neurotrophic factors that facilitate the process of brain repair. However, obtaining sufficient anti-inflammatory microglia/macrophages from the human central nervous system is challenging. Bone marrow-derived inducible microglia-like cells (BM-iMGs) with an anti-inflammatory microglial phenotype were explored to induce neuroprotective properties. Here, we transplanted BM-iMGs into the brain of middle cerebral artery occlusion (MCAO) model male mice to explore their potential for treating chronic ischemic stroke. Methods: Bone marrow-derived mononuclear cells (BM-MNCs) were isolated from green fluorescent protein mice and incubated with granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-4 to induce BM-iMGs with an anti-inflammatory phenotype. BM-iMGs were transplanted into the brains of mice on day 14 after MCAO, and behavioral tests, histology, cerebral blood flow, and gene expression were evaluated. Results: An intracranial injection of BM-iMGs promoted neurobehavioral recovery, reduced neuronal cell loss, suppressed neuroinflammatory astrocytic and microglial responses in the brain, and increased cortical surface cerebral blood flow in MCAO mice. Furthermore, neuroprotective genes were upregulated, whereas proinflammatory genes were downregulated. Conclusions: The intracranial injection of BM-iMG cells shows significant potential as a novel therapy for chronic ischemic stroke. Full article

Ischemic stroke is the most common type of stroke and poses a major global health challenge due to its high mortality and lasting disability impact. The onset and progression of ischemic stroke are largely linked to oxidative stress and inflammatory responses. Alpinetin, a natural flavonoid found in the ginger family, exhibits various pharmacological properties, including antioxidant and anti-inflammatory activities. In this study, the neuroprotective potential of alpinetin in attenuating oxidative stress and inflammation against cerebral ischemic stroke was evaluated. Ninety male Wistar rats were randomly assigned to the sham operation group, the Rt.MCAO group, the Rt.MCAO+piracetam group, and the Rt.MCAO+alpinetin groups (25, 50, and 100 mg/kg BW). Cerebral infarction size, neuronal density, and antioxidant and anti-inflammatory activities were measured. Three days of treatment with alpinetin markedly reduced the infarct volume by 30% compared to the Rt.MCAO+vehicle-treated group. Additionally, rats treated with alpinetin exhibited a significant increase in neuronal density in the cortex, as well as in the CA1 and CA3 regions of the hippocampus. Furthermore, treatment with alpinetin ameliorated both the Rt.MCAO-induced increase in malondialdehyde (MDA) activity and the Rt.MCAO-induced decrease in catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in the cortex and hippocampus. Moreover, COX-2 and IL-6 protein levels were assessed using western blotting. The results showed that treatment with alpinetin (100 mg/kg BW) significantly reduced the expression levels of COX-2 and IL-6 in both the cortex and hippocampus. Our findings suggest that alpinetin significantly mitigates the effects of cerebral ischemia-induced brain damage through its antioxidant and anti-inflammatory properties and could potentially be developed as a therapeutic agent for stroke treatment. Full article

Non-traumatic intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke; however, there are no effective pharmacological therapies available following the insult. Angiogenesis appears as a key step to overcoming the damage and promoting functional recovery. In this context, endothelial progenitor cells (EPCs) mobilization improves oxidative stress and promotes neovascularization, which has been linked to beneficial outcomes following both ischemic and hemorrhagic stroke. The TNF-like weak inducer of apoptosis (TWEAK), binding to its receptor Fn14, has been suggested as an inducer of EPCs differentiation, viability and migration to the injury site in a model of myocardial infarction. Here, we have performed a proof-of-concept preclinical study in a rat model of ICH where we report that a 50 μg/kg dose of rat recombinant TWEAK (rTWEAK) promotes blood progenitor cells mobilization, mainly EPCs. As soon as 72 h post-injury, brain neovascularization, and, importantly, long-term hematoma reduction and improved functional recovery is reported. In contrast, a higher dose of 150 μg/kg blocked those beneficial outcomes. Therefore, a low dose of rTWEAK treatment promotes neovascularization and reduces brain damage in a rat model of ICH. Further clinical studies will be needed to demonstrate if rTWEAK could represent a new strategy to promote recovery following ICH. Full article

Background and Objectives: Despite the latest advancements in interventional procedures and pharmacological therapy, the incidence of heart failure and death rate following an acute myocardial remain unacceptably high. This study was designed in response to the limited and conflicting literature data regarding the diagnostic and prognostic role of modern inflammatory biomarkers in patients with coronary artery disease. Materials and Methods: We conducted a case–control, prospective observational study. A total of 145 patients were analyzed, of whom 105 patients had an acute coronary syndrome diagnosis and represented the study group, while 40 patients with a chronic coronary syndrome diagnosis represented the control group. This study investigates the diagnostic and prognostic role of the interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), Growth differentiation factor 15 (GDF-15), and classic biomarkers in patients with ischemic coronary heart disease. Results: IL-1β exhibited a prognostic role, being significantly correlated with a left ventricular ejection fraction below 30%. GDF-15 plays a dual role, as a cardio-inflammatory biomarker, being significantly correlated with both N-terminal pro-brain natriuretic peptide (NT-proBNP), and IL-1β, IL-6, and CRP. At the same time, GDF-15 represents a surrogate marker for renal dysfunction. According to the ROC analysis, patients at high mortality risk can be identified with adequate accuracy by cardiac troponin, GDF-15, and IL-10, in addition to NT-proBNP. Logistic regression models confirmed NT-proBNP and IL-10 as mortality predictors. Conclusions: IL-1β stands out for its significant prognostic role, while IL-6 did not demonstrate a diagnostic or prognostic role in acute myocardial infarction patients. IL-10 demonstrated superior predictive value in terms of fatal prognosis compared with the other modern biomarkers. GDF-15 is representative of a multivalent biomarker involved in inflammation, heart failure, and renal dysfunction. Full article

Introduction: Traumatic brain injury (TBI) involves a diverse group of head blunt and/or penetrating injuries and is a leading cause of death in the U.S., accounting for one-third of all injury-related deaths. A post-injury hyperglycemic state may commonly impact TBI prognosis and strongly correlate with injury severity. Diabetes mellitus (DM) may also be a source of concomitant hyperglycemia that can worsen prognosis, with previous literature suggesting that DM could be an independent predictor of poor outcome and mortality after TBI. Methods: Using the multi-center, national TriNetX database, we performed a propensity score-matched analysis of severe TBI patients with (DM) and without DM (NDM) from 2014 to 2024. We examined the risk of mortality and complications, including sepsis, cerebral infarction, and pulmonary embolism. We also performed a sub-group analysis comparing the risk of mortality and complications between patients with either insulin-dependent or insulin-independent forms of DM. Results: A total of 26,019 patients were included (4604 DM vs. 21,415 NDM). After propensity score matching, patients with DM had a significantly lower risk of mortality (RR: 0.815; 95% CI: 0.771–0.861; p < 0.05) and ventilator dependency (RR: 0.902; 95% CI: 0.844–0.963; p < 0.05) compared to NDM patients. However, patients with DM had a significantly higher risk of cerebral infarctions, seizures, pneumonia, and sepsis (p < 0.05). Sub-group analysis found no significant difference in mortality or complications between insulin-dependent and insulin-independent forms of DM. Conclusion: Our results suggest that hyperglycemia secondary to DM plays a complicated role in the outcomes after severe TBI. Unexpectedly, we identified both increased and decreased complications in patients with DM. These results reflect the current challenges in the literature surrounding pre-existing DM in patients’ outcomes, the impact of diabetic medications on patient outcomes, and the changing role of aggressive glucose management in critical care patients. Full article

Ischemic stroke is a leading cause of death and disability worldwide. Currently, there is an unmet clinical need for pharmacological treatments that can improve ischemic stroke outcomes. In this study, we investigated the role of brain peroxisome proliferator-activated receptor alpha (PPARα) in ischemic stroke pathophysiology. We used a well-established model of cerebral ischemia in PPARα transgenic mice and conducted the RNA sequencing (RNA-seq) of mouse stroke brains harvested 48 h post-middle cerebral artery occlusion (MCAO). PPARα knockout (KO) increased brain infarct size following stroke, indicating a protective role of PPARα in brain ischemia. Our RNA-seq analysis showed that PPARα KO altered the expression of genes in mouse brains with known roles in ischemic stroke pathophysiology. We also identified many other differentially expressed genes (DEGs) upon the loss of PPARα that correlated with increased infarct size in our stroke model. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis revealed the upregulation of gene signatures for the positive regulation of leukocyte proliferation, apoptotic processes, acute-phase response, and cellular component disassembly in mouse stroke brains with PPARα KO. In addition, pathway analysis of our RNA-seq data revealed that TNFα signaling, IL6/STAT3 signaling, and epithelial–mesenchymal transition (EMT) gene signatures were increased in PPARα KO stroke brains. Our study highlights PPARα as an attractive drug target for ischemic stroke due to its transcriptional regulation of inflammation-, apoptosis-, and EMT-related genes in brain tissue following ischemia. Full article

Vascular dementia (VaD) is a heterogeneous group of brain disorders caused by cerebrovascular pathologies and the second most common cause of dementia, accounting for over 20% of cases and posing an important global health concern. VaD can be caused by cerebral infarction or injury in critical brain regions, including the speech area of the dominant hemisphere or arcuate fasciculus of the dominant hemisphere, leading to notable cognitive impairment. Although the exact causes of dementia remain multifactorial and complex, oxidative stress (reactive oxygen species), neuroinflammation (TNFα, IL-6, and IL-1β), and inflammasomes are considered central mechanisms in its pathology. These conditions contribute to neuronal damage, synaptic dysfunction, and cognitive decline. Thus, antioxidants and anti-inflammatory agents have emerged as potential therapeutic targets in dementia. Recent studies emphasize that cerebrovascular disease plays a dual role: first, as a primary cause of cognitive impairment and then as a contributor to the manifestation of dementia driven by other factors, such as Alzheimer’s disease and other neurodegenerative conditions. This comprehensive review of VaD focuses on molecular mechanisms and their consequences. We provided up-to-date knowledge about epidemiology, pathophysiological mechanisms, and current therapeutic approaches for VaD. Full article