Search Results (576)

Background and Objectives: Systemic inflammatory markers from an ordinary complete blood count (CBC) may foreshadow where non-small-cell lung cancer (NSCLC) will first spread, but organ-specific signatures remain poorly defined. Materials and Methods: We retrospectively reviewed 302 adults (mean age 60.7 ± 13.4 years; 80.8% men) with stage IV NSCLC managed at OncoHelp Medical Center, Timișoara, between January 2022 and December 2024. Eligibility demanded a single radiologically confirmed distant site at diagnosis and pre-treatment CBC. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) ratios were compared across pleural (n = 52), bone (n = 86), liver (n = 66), and brain (n = 98) metastases using Kruskal–Wallis tests with Bonferroni adjustment; z-standardized logistic models identified independent predictors. Results: Metastases clustered most often in brain (32.5%), followed by bone (28.5%), liver (21.9%), and pleura (17.2%). Median PLR rose selectively in pleural disease (274 vs. 217–253 in other sites; p = 0.006). LMR fell to 2.0 in bone but climbed to 2.8 in brain lesions (p = 0.032 and 0.008, respectively). NLR was globally elevated (6.7–7.6), yet differed significantly only for bone and liver deposits. Logistic modeling showed that each standard-deviation rise in absolute neutrophil count quadrupled the odds of hepatic involvement (Odd Ratio (OR) 4.26; 99% Confidence inerval (CI) 2.20–6.25), monocytosis nearly doubled bone risk (OR 1.83; 1.01–3.33), while higher erythrocytes, eosinophils, and lymphocytes independently protected against pleural seeding (all p < 0.01). Age-stratified analysis revealed that osseous and cerebral metastases predominated in patients ≤ 50 years, whereas inflammatory indices were age-invariant. Conclusions: Routine CBC ratios encode distinct “inflammatory fingerprints” that mirror the first metastatic destination in NSCLC: platelets herald pleural spread, neutrophils favor liver and bone, and divergent lymphocyte–monocyte balances separate bone from brain. Although no substitute for cross-sectional imaging, these low-cost markers could refine clinical suspicion, guide targeted work-up, and illuminate the biology of organ-selective dissemination, particularly in resource-limited settings. Full article

Blood–brain barrier (BBB) deterioration with increasing age is an important factor contributing to vascular dementia. Previous studies show that endothelial nitric oxide synthase (eNOS) facilitates vascular endothelial growth factor-mediated angiogenesis and increased vascular permeability. In contrast, recent work has shown that aged hemi-deficient hemizygous eNOS^+/− mice manifest BBB disruption in association with increased incidence of thromboembolic events in the brain. To unravel whether eNOS contributes to or protects against hypoxia-induced cerebrovascular damage, we compared chronic mild hypoxia (CMH)-induced cerebrovascular angiogenic remodeling and BBB breakdown in aged (20 months old) eNOS^+/− and wild-type (WT) mice. This revealed that CMH strongly enhanced eNOS expression in cerebral blood vessels with much lower levels in eNOS^+/− mice. eNOS hemi-deficiency resulted in greater CMH-induced BBB disruption, but unexpectedly, had no effect on endothelial proliferation. eNOS^+/− mice also displayed enhanced endothelial expression of the endothelial activation markers MECA-32, VCAM-1, and β3 integrin in cerebral blood vessels, indicating greater vascular inflammation, and this correlated with increased levels of microglial activation and demyelination. Taken together, our results support the concept that eNOS plays an important protective function in the aged brain by suppressing endothelial activation and maintaining cerebrovascular health. Full article

Background: Cerebral palsy (CP) is a lifelong neurodevelopmental disorder characterised by motor impairment and commonly associated with comorbidities such as cognitive, communicative, and behavioural difficulties. While the physical and functional aspects of CP have been extensively studied, the mental health needs of this population remain largely underexplored, particularly concerning suicidal ideation and self-injurious behaviours. The purpose of this review is to synthesise the existing literature on suicidality in individuals with CP, explore theoretical and clinical risk factors, and identify key gaps in the current evidence base. Methods: A narrative literature review was conducted focusing on studies addressing suicidal ideation, self-harm, or related psychiatric outcomes in individuals with CP. Additional literature on risks and protective factors was included to support theoretical inferences and clinical interpretations. Results: Only a limited number of studies addressed suicidality directly in CP populations. However, several reports document elevated rates of depression, anxiety, and emotional distress, particularly among adults and individuals with higher levels of functioning. Communication barriers, chronic pain, social exclusion, and lack of accessible mental health services emerged as critical risk factors. Protective elements included strong family support, inclusive environments, and access to augmentative communication. Conclusions: Suicidality in individuals with CP is a neglected yet potentially serious concern. Evidence suggests underdiagnosis due to factors such as communication barriers and diagnostic overshadowing. Future research should prioritise disability-informed methodologies and validated tools for suicidal ideation, while clinicians should incorporate routine, adapted mental health screening in CP care to ensure early detection and person-centred management. 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: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article

Cerebral ischemic-reperfusion injury (CIRI) involves mitochondrial dysfunction, with mitophagy playing a key role. Astragaloside IV (AS-IV) shows neuroprotective potential; however, its mechanisms related to mitochondrial function and apoptosis remain unclear. Methods: Using a rat MCAO/R model, we evaluated the AS-IV’s effects via neurological scores, TTC staining, and histopathology. Molecular assays and docking were used to analyze mitophagy (PINK1, Parkin, p62, ROS, Bcl-2, and BAX) and apoptosis markers. Results: AS-IV improved neurological function, reduced infarct volume, and alleviated neuronal/mitochondrial damage. It upregulated PINK1/Parkin, decreased p62, and modulated Bcl-2/Bax. Docking confirmed AS-IV binds PINK1/Parkin with high affinity. Conclusions: AS-IV protects against CIRI by regulating the PINK1/Parkin pathway, improving mitochondrial function, and inhibiting neuronal apoptosis, providing an experimental basis for the clinical use Full article

Cerebral malaria (CM) is the severe progression of an infection with Plasmodium falciparum, causing detrimental damage to brain tissue and is the most frequent cause of Plasmodium falciparum mortality. The critical role of brain-infiltrating CD8⁺ T cells in the pathophysiology of CM having been revealed, our investigation focuses on the role of NR2F6, an established immune checkpoint, as a candidate driver of CM pathology. We employed an experimental mouse model of CM based on Plasmodium berghei ANKA (PbA) infection to compare the relative susceptibility of Nr2f6-knock-out and wild-type C57BL6/N mice. As a remarkable result, Nr2f6 deficiency confers a significant survival benefit. In terms of mechanism, we detected less severe endotheliopathy and, hence, less damage to the blood–brain barrier (BBB), accompanied by decreased sequestered parasites and less cytotoxic T-lymphocytes within the brain, manifesting in a better disease outcome. We present evidence that NR2F6 deficiency renders mice more resistant to experimental cerebral malaria (ECM), confirming a causal and non-redundant role for NR2F6 in the progression of ECM disease. Consequently, pharmacological inhibitors of the NR2F6 pathway could be of use to bolster BBB integrity and protect against CM. Full article

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article

Background/Objectives: Cerebral hemorrhage (CH) has physical, cognitive, and emotional consequences. Recovery requires a complex rehabilitation process in which coping strategies play a fundamental role in supporting psychological adaptation. The aim of this study is to investigate and understand the extent and manner in which coping strategies have been assessed in the CH population within the scientific literature. Methods: Studies were identified through searches in the PubMed, Scopus, and Embase databases. Eight studies published between 2014 and 2024 were selected. Results: The most frequently adopted coping strategies include task-oriented coping, avoidance, emotion-focused coping, acceptance, planning, and emotional support. Task-oriented strategies and acceptance are associated with better psychological outcomes. Conversely, avoidant and emotion-focused strategies correlate with higher levels of anxiety, depression, and poorer adaptation. Resilience and social participation emerge as protective factors. Finally, Action/Distraction is associated with a better quality of life, while Trivialization/Resignation is linked to lower levels. Conclusions: Coping seems to represent a modifiable, patient-centered lever that can mitigate the psychosocial sequelae of intracranial hemorrhage when assessed systematically and addressed through tailored rehabilitation programs. Our findings lay the groundwork for evidence-based, coping-focused interventions and highlight critical avenues for future longitudinal and mechanistic research. Full article

Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance analysis using data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Reports up to May 2025 listing an SSRI (sertraline, fluoxetine, paroxetine, escitalopram, citalopram, or fluvoxamine) as a suspect or interacting drug and involving an ICH event were included. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals. Results: Among 226 eligible ICH cases, sertraline (30.5%), paroxetine (28.8%), and fluoxetine (27.9%) were most frequently implicated. Sertraline showed a strong signal for cerebral hemorrhage (ROR = 4.97), while fluoxetine was associated with subarachnoid hemorrhage (ROR = 4.51). Sertraline had a pronounced signal among patients aged >60 years (ROR = 7.92) and in combination with anticoagulants (ROR = 9.56). Fluoxetine was underrepresented in elderly cases. Given the very small number of fluvoxamine-related cases (n = 2), interpretation should be cautious due to limited statistical power. Gender-stratified analyses showed female predominance in sertraline-related ICH and male predominance for paroxetine. Citalopram demonstrated a potentially protective profile with inverse association with cerebral hemorrhage. Conclusions: This study highlights significant differences in ICH reporting patterns across SSRIs, modified by patient age, gender, and co-medication. These findings underscore the need for individualized SSRI prescribing, particularly in patients receiving anticoagulant therapy particularly in elderly patients and those receiving anticoagulant therapy, where sertraline and fluoxetine may pose increased risk. Full article

This study aims to investigate the mechanism by which the total flavones of Rhododendron (TFR) protect against cerebral ischemic injury through the endothelial-derived H₂S-mediated regulation of RhoA phosphorylation at the Ser188 and Rho kinase 2 (ROCK₂) phosphorylation at Thr436. For experimental design, mouse or rat cerebrovascular endothelial cells (ECs) were cultured with or without neurons and subjected to hypoxia/reoxygenation (H/R) injury. The vasodilation of the cerebral basilar artery was assessed. Cerebral ischemia/reperfusion (I/R) injury was induced in mice by bilateral carotid artery ligation, followed by Morris water maze and open field behavioral assessments. The protein levels of cystathionine-γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), RhoA, ROCK₂, p-RhoA (RhoA phosphorylated at Ser188), and p-ROCK₂ (ROCK₂ phosphorylated at Thr436) were quantified. Additionally, the activities of RhoA and ROCK₂ were measured. Notably, TFR significantly inhibited H/R-induced H₂S reduction and suppressed the increased expression and activity of RhoA and ROCK₂ in ECs, effects attenuated by CSE or 3-MST knockout. Moreover, TFR-mediated cerebrovascular dilation was reduced by RhoA or ROCK₂ inhibitors, while the protective effect of TFR against cerebral I/R injury in mice was markedly attenuated by the heterozygous knockout of ROCK₂. In the ECs-co-cultured neurons, the inhibition of TFR on H/R-induced neuronal injury and decrease in H₂S level in the co-culture was attenuated by the knockout of CSE or 3-MST in the ECs. TFR notably inhibited the H/R-induced upregulation of neuronal RhoA, ROCK₂, and p-ROCK₂ protein levels, as well as the activities of RhoA and ROCK₂, while reversing the decrease in p-RhoA. However, the knockout of CSE or 3-MST in the ECs significantly attenuated the inhibition of TFR on these increases. Furthermore, 3-MST knockout in ECs attenuated the TFR-mediated suppression of p-RhoA reduction. Additionally, CSE or 3-MST knockout in ECs exacerbated H/R-induced neuronal injury, reduced H₂S level in the co-culture system, and increased RhoA activity and ROCK₂ expression in neurons. In summary, TFR protected against ischemic cerebral injury by endothelial-derived H₂S promoting the phosphorylation of RhoA at Ser188 but inhibited the phosphorylation of ROCK₂ at Thr436 to inhibit the RhoA-ROCK₂ pathway in neurons. 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

Glutamate is an excitatory neurotransmitter in the central nervous system (CNS) that mediates synaptic transmission. However, glutamate homeostasis among neural cells is broken in cerebral ischemia. Excessive glutamate triggers N-methyl-d-aspartate receptors (NMDARs) in postsynaptic neurons, leading to intracellular calcium (Ca²⁺) overload and excitoneurotoxicity. At this moment, L-lactate may affect NMDARs and play a protective role in cerebral ischemia. This work proposes that L-lactate regulates glutamate signaling among neural cells. But, dysregulation of L-lactate in glutamate signaling cascades contributes to glutamate excitotoxicity in cerebral ischemia. In detail, L-lactate regulates the glutamine(Gln)-glutamate cycle between astrocytes and presynaptic neurons, which triggers the astroglial L-lactate-sensitive receptor (LLR)-cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway, coordinating astroglial glutamate uptake and neuronal glutamate transmission. L-lactate mediates glutamate signaling and synaptic transmission among neural cells. In addition, L-lactate promotes the function of mitochondrial calcium uniporter complex (MCUC), which quickly depletes intracellular Ca²⁺ in postsynaptic neurons. In addition, L-lactate can promote the conversion of microglia from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype. Therefore, regulation of L-lactate in glutamate signaling in the CNS might become a preventive target for cerebral ischemia. Full article

Transcatheter aortic valve implantation (TAVI) has emerged as a transformative therapy for patients with severe aortic stenosis (AS) across all surgical risk groups. However, periprocedural cerebrovascular events (CVEs), including overt stroke and silent cerebral embolism, remain significant complications. As a result, the use of embolic protection devices (EPDs) during TAVI has been proposed to mitigate this risk. Our aim was to provide a comprehensive review of the current evidence on the efficacy, safety, and clinical utility of embolic protection devices in TAVI procedures. According to the existing literature, EPDs are effective in capturing embolic debris during TAVI and are associated with a reduction in silent cerebral lesions as detected by diffusion-weighted MRI. While some RCTs and meta-analyses demonstrate a potential benefit in reducing disabling stroke, evidence for a consistent reduction in overall stroke or mortality remains inconclusive. Subgroup analyses suggest the greatest benefit in patients at elevated stroke risk, while current-generation EPDs demonstrate high technical success and an acceptable safety profile. Subsequently, EPDs represent a promising adjunct to TAVI, particularly in high-risk populations. However, routine use in all patients is not yet supported by consistent clinical evidence. Further large-scale trials and long-term outcome data are needed to clarify their role in improving neurological outcomes and to guide selective patient application. Full article