Search Results (605)

Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article

Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H₂O₂-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H₂O₂-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu’s protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H₂O₂-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia–reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP −1.16 ± 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via •OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H₂O₂-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 μM) and inhibited excessive cell ROS generation (45.67% at 100 μM). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS. Full article

Due to the stroke-protective effects of dietary fiber and anthocyanin together with the synergistic interaction, we hypothesized that the functional drink containing the anthocyanins and dietary fiber-enriched functional ingredient from banana and germinated black Jasmine rice (BR) should protect against ischemic stroke. BR at doses of 300, 600, and 900 mg/kg body weight (BW) was orally given to male Wistar rats weighing 290–350 g once daily for 21 days, and they were subjected to ischemic reperfusion injury induced by temporary occlusion of the middle cerebral artery (MCAO/IR) for 90 min. The treatment was prolonged for 21 days after MCAO/IR. They were assessed for brain infarction volume, neuron density, Nrf2, MDA, and catalase in the cortex together with serum TNF-α and IL-6. Lactobacillus and Bifidobacterium spp. in feces were also assessed. Our results showed that BR improved the increase in brain infarcted volume, MDA, TNF-α, and IL-6 and the decrease in neuron density, Nrf2, catalase, and both bacteria spp. induced by MCAO/IR. These data suggest the stroke-protective effect of the novel functional drink, and the action may involve the improvement of Nrf2, oxidative stress, inflammation, and the amount of Lactobacillus and Bifidobacterium spp. Full article

Background/objectives: Being overweight increases the predisposition to obesity and type 2 diabetes (T2D), which significantly elevate stroke risk and the likelihood of severe post-stroke disability. Dietary nitrate (NO₃⁻) supplementation can mitigate obesity and metabolic impairments, making it a promising approach to halt overweight people from developing overt obesity/T2D, thereby potentially also improving stroke outcome. We determined whether NO3⁻ supplementation prevents overweight mice from progressing into obesity and T2D and whether this intervention improves stroke outcome. Methods: An overweight condition was induced via 6 weeks of a high-fat diet (HFD), after which animals were randomized to either a HFD or a HFD with NO₃⁻ supplementation. After 24 weeks, when HFD-mice without NO₃⁻ developed obesity and T2D, all animals were subjected to transient middle cerebral artery occlusion and stroke outcome was assessed via behavioral testing and infarct size. The effect of NO₃⁻ on post-stroke neuroinflammation, neurogenesis, and neovascularization was analyzed by immunohistochemistry. Results: Sustained NO₃⁻ supplementation in overweight mice did not prevent obesity or insulin resistance. However, it attenuated weight gain, prevented hyperglycemia, and significantly improved functional recovery after stroke, without affecting infarct size. Moreover, NO₃⁻ decreased post-stroke neuroinflammation by reducing microglial infiltration. NO₃⁻ did not affect stroke-induced neurogenesis or vascularization. Conclusion: These results highlight the potential of NO₃⁻ supplementation to prevent metabolic impairment in the overweight population and improve stroke prognosis in this large group of people at risk of stroke and severe stroke sequelae. Full article

MRI perfusion is used to diagnose and monitor neurological conditions such as brain tumors, stroke, dementia, and traumatic brain injury. Dynamic Susceptibility Contrast (DSC) is the most widely available quantitative MRI technique for perfusion imaging. Even in its most basic implementation, DSC MRI provides critical hemodynamic metrics like cerebral blood flow (CBF), blood volume (CBV), mean transit time (MTT), and time between the peak of arterial input and residue function (Tmax), through the dynamic tracking of a gadolinium-based contrast agent. Notwithstanding its high clinical importance and widespread use, the reproducibility and diagnostic reliability are impeded by a lack of standardized pre-processing protocols and quality controls. A comprehensive literature review and the authors’ aggregated experience identified common DSC MRI artefacts and corresponding pre-processing methods. Pre-processing methods to correct for artefacts were evaluated for their practical applicability and validation status. A consensus on the pre-processing was established by a multidisciplinary team of experts. Acquisition-related artefacts include geometric distortions, slice timing misalignment, and physiological noise. Intrinsic artefacts include motion, B₁ inhomogeneities, Gibbs ringing, and noise. Motion can be mitigated using rigid-body alignment, but methods for addressing B₁ inhomogeneities, Gibbs ringing, and noise remain underexplored for DSC MRI. Pre-processing of DSC MRI is critical for reliable diagnostics and research. While robust methods exist for correcting geometric distortions, motion, and slice timing issues, further validation is needed for methods addressing B₁ inhomogeneities, Gibbs ringing, and noise. Implementing adequate mitigation methods for these artefacts could enhance reproducibility and diagnostic accuracy, supporting the growing reliance on DSC MRI in neurological imaging. Finally, we emphasize the crucial importance of pre-scan quality assurance with phantom scans. 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

Ischemic stroke following percutaneous coronary intervention (PCI) is a rare complication, with an overall incidence of 0.56%. Most embolic strokes result from the dislodgement of atherosclerotic plaques, thrombi formed on catheter surfaces, procedural maneuvers, or, less commonly, air or metallic emboli originating from fractured guidewires. We present a unique case of stroke following PCI due to a previously unreported mechanism—arterial tunica media embolization associated with arterial access. A 57-year-old female presented with chest pain at rest and with exertion, accompanied by episodes of anxiety and fluctuating blood pressure, for which coronary angiography was performed, revealing 90–99% stenosis of the left anterior descending artery and necessitating PCI. During the procedure, the patient developed an eye deviation, aphasia, and left-sided hemiparesis. Cerebral angiography identified a M2 segment occlusion of the right middle cerebral artery (MCA) and a subocclusion of the right anterior cerebral artery (ACA). Thrombectomy was performed, retrieving two white, tubular emboli resembling fragments of a vessel wall, histologically confirmed to be arterial tunica media. While PCI is associated with a low complication rate, its increasing frequency necessitates awareness of emerging complications. This case underscores a previously undocumented potential embolic complication arising from the performance of PCI. Full article

In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. Previously, a significant effect of non-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides on the functions of the nervous system was shown. Also, while using RNA-Seq, we firstly revealed differentially expressed genes (DEGs) that associated with peptides in the penumbra-associated region of the frontal cortex (FC) of rats at 24 h after transient middle cerebral artery occlusion (tMCAO) model. Peptides significantly reduced profile disturbances caused by ischemia for almost two-thousand DEGs in FC related to the neurotransmitter and inflammatory response. Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly. The same animals from which we previously acquired FC were used to collect striatum samples. Peptides generated fewer DEGs in the striatum than in the FC. Both peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of DEGs, whereas 152 genes showed an even more affected profile in the striatum under ACTH(6-9)PGP action. These DEGs were associated with inflammation, predominantly. About hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction, predominantly. Thus, genes that are associated with the ACTH-like peptide action in rat brain regions with varying levels of ischemia injury were identified. Moreover, differential spatial regulation of the ischemia process in the rat brain at the transcriptome levels was discovered under peptides with different ACTH structures. We suppose that our results may be useful for selecting more effective neuroprotective drug structures in accordance with their specific tissue/damage therapeutic impact. Full article

ABCC6, a key regulator in ectopic calcification, plays a crucial role in mineralization through the modulation of extracellular purinergic pathways and production of inorganic pyrophosphate (PPi), which inhibits calcification. Inherited deficiencies in ABCC6 lead to pseudoxanthoma elasticum (PXE) and related conditions, characterized by calcification in various tissues, particularly affecting the skin, eyes, and cardiovascular system. Although PXE does not directly impact the nervous system, secondary neurological issues arise from cerebrovascular complications, increasing the risk of strokes linked to arterial blockages resembling atherosclerosis. This review investigates the connection between ABCC6 mutations and cerebral small vessel disease (SVD), expanding the understanding of PXE and related phenotypes. Mutations in ABCC6, identified as causing PXE, contribute to systemic metabolic dysfunction, with significant implications for cerebrovascular health. An association between ABCC6 mutations and cerebral SVD has been suggested in various studies, particularly in populations with distinct genetic backgrounds. Emerging evidence indicates that pathogenic mutations increase the risk of ischemic strokes, with both homozygous and heterozygous carriers showing susceptibility. Mechanistically, ABCC6 deficiency is implicated in dyslipidemia and atherosclerosis, further exacerbating cerebrovascular risks. Increased arterial pulsatility, linked to carotid siphon calcification, may also contribute to microvascular damage and subsequent brain injury. Understanding these mechanisms is vital for developing targeted diagnostic and therapeutic strategies for managing cerebrovascular risks in PXE patients. This review emphasizes the need for comprehensive genetic screening and the consideration of traditional vascular risk factors in patient management, highlighting the complex interplay between genetic mutations and environmental influences affecting cerebrovascular health. Future research should focus on longitudinal studies to elucidate the causal pathways linking arterial calcification, pulsatility, and brain damage in PXE. Full article

Background/Objectives: Assessment of the hemodynamic status of the brain in patients with cerebrovascular diseases is crucial for providing valuable clinical information. Various magnetic resonance perfusion sequences are used in studies, and one of the current challenges is comparing methods utilizing exogenous and endogenous contrast. This meta-analysis aimed to evaluate the correlation between arterial spin labeling (ASL)-derived perfusion parameters and those obtained by dynamic susceptibility contrast (DSC) perfusion in stroke and steno-occlusive diseases. Methods: A systematic review and meta-analysis were conducted, including 14 studies that reported correlation coefficients between perfusion MRI sequences in the assessment of stroke or steno-occlusive diseases. The correlation between ASL-derived cerebral blood flow (ASL-CBF) and DSC-derived cerebral blood flow (DSC-CBF) was analyzed, considering different magnetic field strengths (1.5 T and 3.0 T), sequence types, and brain regions. Additionally, real and normalized data were compared. Results: A moderate positive correlation was found between ASL-CBF and DSC-CBF (R = 0.464). Subgroup analysis demonstrated that ASL-CBF and DSC-CBF correlated at 3.0 T (R = 0.401) and 1.5 T (R = 0.700). No significant differences were observed in correlation coefficients based on sequence type or brain region. Normalized data demonstrated a higher correlation coefficient compared to real data (Rreal = 0.393, Rnorm = 0.496). Additionally, the correlation coefficient between ASL-CBF and DSC-derived mean transit time (DSC-MTT) for all included studies was R = −0.422. Conclusions: ASL-derived perfusion parameters demonstrate moderate-to-high agreement with DSC perfusion parameters in stroke and steno-occlusive patients. These findings support the potential utility of ASL as a non-invasive alternative to DSC perfusion imaging in clinical and research settings. Full article

Accurate segmentation of brain vessels is critical for diagnosing cerebral stroke, yet existing AI-based methods struggle with challenges such as small vessel segmentation and class imbalance. To address this, our study proposes a novel 2D segmentation method based on the nnUNet framework, enhanced with MedSAM/MedSAM2 features, for arterial vessel segmentation in time-of-flight magnetic resonance angiography (TOF-MRA) brain slices. The approach first constructs a baseline segmentation network using nnUNet, then incorporates MedSAM/MedSAM2’s feature extraction module to enhance feature representation. Additionally, focal loss is introduced to address class imbalance. Experimental results on the CAS2023 dataset demonstrate that the MedSAM2-enhanced model achieves a 0.72% relative improvement in Dice coefficient and reduces HD95 (mm) and ASD (mm) from 48.20 mm to 46.30 mm and from 5.33 mm to 4.97 mm, respectively, compared to the baseline nnUNet, showing significant enhancements in boundary localization and segmentation accuracy. This approach addresses the critical challenge of small vessel segmentation in TOF-MRA, with the potential to improve cerebrovascular disease diagnosis in clinical practice. Full article

Background: Ischemic stroke (IS) is probably the most important acute serious illness, where interdisciplinary approach is essential to offer the best chance for survival and functional recovery of patients. Carbon dots (CDs) with multifaceted advantages have provided hope for development brand-new nanodrug for treating thorny diseases. Methods: This study developed a green and environmentally responsible calcination method to prepare novel Gardenia jasminoides Carbonisata (GJC-CDs) as promising drug for ischemic stroke treatment. Results: In this work, we isolated and characterized for the first time a novel carbon dots (GJC-CDs) from the natural plant G. jasminoides. Results displayed that green GJC-based CDs with tiny sizes and abundant functional groups exhibited solubility, which may be beneficial for its settled biological activity. The neuroprotective effect of carbon dots from G. jasminoides were evaluated using the classical middle cerebral artery occlusion (MCAO) model. Assessing the infarct volume content of the ischemic cerebral hemisphere and determining the serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels of the mice in each group, it was evident that pre-administration of the drug by GJC-CDs significantly reduced the infarct volume as well as attenuated inflammatory responses and excessive oxidative stress in MCAO mice. Furthermore, in vitro cellular experiments demonstrated that GJC-CDs have good biosafety and anti-inflammatory and antioxidant capacity. Conclusions: Overall, GJC-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, which not only provides evidence for further broadening the biological application of acute ischemic stroke but also offers novel strategy for the application of nanomedicine to treat acute diseases. 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