Search Results (144)

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

Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context of the COVID-19 pandemic, contradictory findings from previous studies that also addressed sex differences in cerebrovascular diseases demonstrate the need for further focused research. This study aimed to evaluate the sex discrepancies in the clinical presentation of IS and its outcomes in patients admitted to Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS), Lithuania. Materials and Methods: This is a retrospective record-based single-center study. All the study patients—727 men and 1082 women—enrolled between 1 January 2020, and 27 February 2022; suffered from acute IS; and had absolute contraindications against interventional IS treatment. These patients received a conservative non-interventional IS treatment at the neurological department of the LUHS’s Kaunas Hospital. The sociodemographic data; laboratory findings; comorbidities, including COVID-19; in-hospital complications; and outcome factors were obtained from the patients’ medical records and evaluated by deploying appropriate statistical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazards regression for in-hospital lethality. Results: The mean age of IS patients was significantly higher in women compared to men (p < 0.001), as was the proportion of in-hospital deaths (19.10% and 15.36%, respectively; p < 0.05). The mean total number of in-hospital complications was again significantly higher in the group of women compared to men (p < 0.05). The prevalence of COVID-19 was higher in men compared to women (p < 0.05). COVID-19 diagnosis (HR = 1.53; p = 0.02) and acute in-hospital pulmonary complications (HR = 1.91; p = 0.008) significantly increased the risk of in-hospital lethality in men. The risk of in-hospital lethality was significantly higher in women with comorbid diabetes mellitus type 2 (DM) compared to those with comorbid isolated arterial hypertension (AH) (HR = 2.25, p = 0.007). Increased C-reactive protein elevated the risk of in-hospital lethality by more than twice in both men and women (HR = 2.46; p < 0.001 and HR = 2.28; p < 0.001, respectively). Conclusions: The following differences between men and women with IS were determined: Acute in-hospital pulmonary complications, including COVID-19, significantly increased the risk of in-hospital lethality in the male group, but not in women. However, women suffering from DM had a significantly increased risk of in-hospital lethality compared with those women IS patients with AH or chronic ischemic heart disease (IHD). Increased C-reactive protein was associated with an elevated risk of in-hospital lethality both in male and female groups. Full article

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood–brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus–immune–brain axis in long COVID and inform effective clinical management. Full article

Arthropod-borne viral infections, ranging from asymptomatic to fatal diseases, are expanding from endemic to nonendemic areas. Climate change, deforestation, and globalization favor their spread. Although arboviral manifestations mainly determine the onset of generalized symptoms, distinct clinical signs have been assessed, depending on the particular arthropod-borne virus (arbovirus) involved in the infectious process. A number of arboviruses cause neuroinvasive diseases in vertebrate hosts, with acute to chronic outcomes. Long-term neurological sequelae can include cognitive dysfunction and Parkinsonism. To increase knowledge of host interactions with arboviruses, in-depth investigations are needed to highlight how arboviruses exploit a host cell for efficient infection and clarify the molecular alterations underlying human brain diseases. This review focuses on the involvement of host cytoskeletal networks and associated signalling pathways in modulating the neurotropism of emerging arboviruses. A better understanding at the molecular level of the potential for emerging infectious diseases is fundamental for prevention and outbreak control. Full article

Multiple sclerosis (MS) is a chronic progressive neurodegenerative disease that leads to disabilities such as difficulty moving and slowed cognitive processing. It is the leading non-traumatic cause of disability worldwide. MS also has a high potential to become a model for neurodegenerative diseases with a progression like Alzheimer’s or Parkinson’s. Cardiovascular diseases (CVDs) remain the leading cause of global deaths and have a considerable economic impact. The higher incidence of cardiovascular comorbidities in patients with MS compared to healthy individuals of the same age worsens the prognosis of neurological pathology, leading to a higher level of disability, poorer physical outcomes, higher depression scores, cognitive aging, and diminished quality of life. Classical observational studies often have questionable elements that can represent a source of error, making it difficult to establish a causal relationship between MS and CVD. Genetic studies, including genome-wide evaluation, may resolve this issue and may represent a topic for future research. We report the case of a 31-year-old male patient with a history of multiple sclerosis (MS) diagnosed seven years prior, who presented with acute chest pain upon returning from vacation. Despite the previous recommendation for disease-modifying therapy, the patient had discontinued treatment by personal choice. Electrocardiography (ECG) revealed ST-segment elevation in inferior leads, and emergent coronary angiography identified severe multi-vessel coronary artery disease (CAD), requiring immediate revascularization. This case highlights the potential cardiovascular risks in young patients with MS and the importance of continuous medical supervision. Full article

Severe Acute Respiratory Syndrome (SARS) represents a significant cause of morbidity and mortality in children under one year of age, a particularly vulnerable population due to immunological and respiratory immaturity. The diverse etiology includes multiple respiratory viruses such as Respiratory Syncytial Virus (RSV), influenza, rhinovirus, and SARS-CoV-2, each with distinct potential to cause severe illness and death. Understanding the specific incidence and lethality by etiological agents in the recent Brazilian context (2024), after the COVID-19 pandemic, is essential to guide surveillance and public health strategies. This study aimed to analyze the risk of incidence and lethality by specific etiology of SARS in children under one year of age hospitalized in Brazil during the year 2024. A descriptive cross-sectional study was performed using secondary data from the 2024 Influenza Epidemiological Surveillance Information System (SIVEP-Gripe), obtained via OpenDataSUS. Reported cases of SARS hospitalized in children <1 year of age in Brazil were included. Distribution by final classification and epidemiological week (EW) was analyzed; the incidence rate by Federative Unit (FU) (cases/100,000 < 1 year) with risk classification (Low/Moderate/High) was assessed; and, for cases with positive viral RT-PCR, the etiological frequency and virus-specific lethality rate (deaths/total cases of etiology ×100), also with risk classification, were extracted. A multivariate logistic regression model was performed for the risk factors of death. A total of 66,170 cases of SARS were reported in children under 1 year old (national incidence: 2663/100,000), with a seasonal peak between April and May. The majority of cases were classified as “SARS due to another respiratory virus” (49.06%) or “unspecified” (37.46%). Among 36,009 cases with positive RT-PCR, RSV (50.06%) and rhinovirus (26.97%) were the most frequent. The overall lethality in RT-PCR-positive cases was 1.28%. Viruses such as parainfluenza 4 (8.57%), influenza B (2.86%), parainfluenza 3 (2.49%), and SARS-CoV-2 (2.47%) had higher lethality. The multivariate model identified parainfluenza 4 (OR = 6.806), chronic kidney disease (OR = 3.820), immunodeficiency (OR = 3.680), Down Syndrome (OR = 3.590), heart disease (OR = 3.129), neurological disease (OR = 2.250), low O₂ saturation (OR = 1.758), SARS-CoV-2 (OR = 1.569) and respiratory distress (OR = 1.390) as risk factors for death. Cough (OR = 0.477) and RSV (OR = 0.736) were associated with a lower chance of death. The model had good calibration (Hosmer–Lemeshow p = 0.693) and overall significance (p < 0.001). SARS represented a substantial burden of hospitalizations, with marked seasonal and geographic patterns. RSV and rhinovirus were the main agents responsible for the volume of confirmed cases but had a relatively low to moderate risk of lethality. In contrast, less frequent viruses such as parainfluenza 4, influenza B, parainfluenza 3, and SARS-CoV-2 were associated with a significantly higher risk of death. These findings highlight the importance of dissociating frequency from lethality and reinforce the need to strengthen etiological surveillance, improve diagnosis, and direct preventive strategies (such as immunizations) considering the specific risk of each pathogen for this vulnerable population. Full article

Neuroinflammation represents a fundamental component in the development and progression of a wide range of neurological disorders, including neurodegenerative diseases, psychiatric conditions, and cerebral injuries. This review examines the complex mechanisms underlying neuroinflammatory responses, with a focus on the interactions between glial cells and neurons. The dualistic role of neuroinflammation is further investigated, highlighting its ability to promote neuroprotection in acute phases while also contributing to neuronal injury and degeneration during chronic activation. This review also considers innovative therapeutic approaches designed to target neuroinflammatory processes, like drug-based treatments and immune-modulating therapies. A thorough understanding of the regulatory balance within neuroinflammatory networks is essential for the development of effective treatments for several neurological pathologies. Finally, this review provides an integrative summary of current evidence and highlights emerging directions in neuroinflammation research. Full article

Background: Sarcopenia is a progressive muscle disorder commonly associated with aging and chronic diseases. It has been linked to worse clinical outcomes and increased vulnerability during acute illness. However, its prevalence in emergency department (ED) populations remains underexplored. This study aimed to evaluate the presence of sarcopenia among ED patients using ultrasound, determine its relationship with underlying comorbidities, and assess its association with in-hospital complications. Methods: We conducted a prospective, observational, cross-sectional study at the Infanta Cristina University Hospital (Madrid, Spain) from January to May 2024. A total of 150 patients aged 18 years and older who presented to the ED were assessed for sarcopenia using rectus femoris ultrasound. Sociodemographic, clinical, and laboratory variables were collected. A multivariate logistic regression model was used to identify independent predictors of in-hospital complications. Patients were followed for 30 days to evaluate outcomes. Comparisons were made between diagnostic groups and sarcopenia indices. Results: The mean age of the cohort was 70.7 years (SD 18.15), and 52% were male. Neurological diseases were associated with the highest degree of sarcopenia (mean Y-axis: 0.93 cm), followed by digestive (1.05 cm), hematological (1.05 cm), and cardiovascular diseases (1.08 cm). Patients who developed in-hospital complications had lower mean muscle thickness values compared to those without complications (1.08 cm vs. 1.24 cm; p < 0.05). Sarcopenia was significantly correlated with the presence of comorbidities and poor clinical outcomes. Conclusions: These findings support the integration of sarcopenia screening protocols into emergency care and highlight the need for studies exploring early nutritional or rehabilitation interventions targeted at high-risk patients. Full article

Background: Complex regional pain syndrome (CRPS) is a rare, chronic, painful, neurological, debilitating disorder. Despite the substantial impact on quality of life, diagnosis remains challenging due to its complex pathophysiology and subjective clinical criteria. This integrative review aims to synthesize current research on potential diagnostic biomarkers for CRPS. Methods: A systematic search was conducted using the PubMed and Scopus databases to identify relevant studies published until January 2025. Inclusion criteria focused on adult CRPS patients, with studies examining diagnostic or predictive biomarkers. Results: Key findings highlight the role of inflammatory and immune-related biomarkers, such as elevated levels of cytokines (IL-6, TNF-α), immune cell infiltration, and specific autoantibodies. Neuropeptides, including substance P and calcitonin gene-related peptide, were associated with pain sensitization in acute phases, though their levels normalized in chronic stages. Additionally, genetic and epigenetic markers, brain imaging, and neurophysiological alterations provided insights into CRPS pathogenesis, emphasizing the dynamic nature of these biomarkers across disease stages. Conclusions: This review underscores the need for further research to integrate these biomarkers into diagnostic frameworks, which could enhance early diagnosis and treatment strategies for CRPS. Full article

Background/Objectives: Infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) poses a significant health risk, especially for individuals with chronic medical conditions. Multiple sclerosis (MS) is the most prevalent chronic, immune-mediated neurological disorder, and vaccinations are essential to its management. This study aimed to compare the reported willingness to be vaccinated against SARS-CoV-2 with the actual vaccination status among people with MS (pwMS) and identify factors explaining the discrepancy. Methods: In a longitudinal, two-center study, we analyzed 149 patients aged 18 or older with a diagnosis of clinically isolated syndrome or MS. The participants completed three surveys: a baseline survey (from June 2019 to June 2020), a pre-vaccine follow-up (from May to July 2020), and a post-vaccine follow-up (from October 2021 to January 2022). The data included sociodemographic, clinical, and psychological information. Results: Among the 149 participants, 122 (81.9%) received a SARS-CoV-2 vaccination, while 27 (18.1%) did not. The pwMS who were unwilling to become vaccinated and remained unvaccinated were less likely to live with a partner, had higher smoking rates, took more medications, had a higher number of previously discontinued disease-modifying therapies, and found pandemic policies inappropriate. No significant associations were found between vaccination willingness/status and factors like age, sex, depression, or anxiety. Conclusions: This study highlights the gap between vaccination willingness and actual status in pwMS, revealing factors associated with vaccine hesitancy. The findings of this study offer insights into addressing vaccine uptake. Full article

Multiple sclerosis is a chronic autoimmune disease in which the immune system attacks the protective sheath or myelin that covers nerve fibers, impacting the brain’s ability to communicate with other areas of the body. This abnormal immune response recruits inflammatory substances, which appear as lesions on the brain and spinal cord. A stroke is characterized by a sudden impairment of neurological function resulting from the loss or restriction of blood flow due to acute damage to a localized area of the central nervous system, including the brain, retina, or spinal cord. While strokes, both ischemic and hemorrhagic, are different in terms of their pathogenesis to MS, mechanisms such as neuroinflammation and neurodegeneration are common denominators among these conditions. Recent studies highlight the involvement of the sphingosine-1-phosphate receptor in the treatment of strokes and how fingolimod, an S1P receptor modulator employed in MS treatment, may play a role in the treatment of stroke-like symptoms. This review aims to explore the potential link between stroke and MS, providing a comprehensive analysis of the existing evidence. It will also shed light on the role of S1P receptors in the pathophysiology of stroke, offering insights into their mechanistic contributions. Furthermore, the review will examine recent studies investigating the therapeutic potential of the S1P modulator, fingolimod, in acute stroke patients, highlighting its efficacy and potential clinical applications. Through this multifaceted approach, we hope to contribute to the development of a deeper understanding of these interconnected neurological conditions and their treatment strategies. Full article

Neuroinflammation is an inflammatory response occurring within the central nervous system (CNS). The process is marked by the production of pro-inflammatory cytokines, chemokines, small-molecule messengers, and reactive oxygen species. Microglia and astrocytes are primarily involved in this process, while endothelial cells and infiltrating blood cells contribute to neuroinflammation when the blood–brain barrier (BBB) is damaged. Neuroinflammation is increasingly recognized as a pathological hallmark of several neurological diseases, including amyotrophic lateral sclerosis (ALS), and is closely linked to neurodegeneration, another key feature of ALS. In fact, neurodegeneration is a pathological trigger for inflammation, and neuroinflammation, in turn, contributes to motor neuron (MN) degeneration through the induction of synaptic dysfunction, neuronal death, and inhibition of neurogenesis. Importantly, resolution of acute inflammation is crucial for avoiding chronic inflammation and tissue destruction. Inflammatory processes are mediated by soluble factors known as cytokines, which are involved in both promoting and inhibiting inflammation. Cytokines with anti-inflammatory properties may exert protective roles in neuroinflammatory diseases, including ALS. In particular, interleukin (IL)-10, transforming growth factor (TGF)-β, IL-4, IL-13, and IL-9 have been shown to exert an anti-inflammatory role in the CNS. Other recently emerging immune regulatory cytokines in the CNS include IL-35, IL-25, IL-37, and IL-27. This review describes the current understanding of neuroinflammation in ALS and highlights recent advances in the role of anti-inflammatory cytokines within CNS with a particular focus on their potential therapeutic applications in ALS. Furthermore, we discuss current therapeutic strategies aimed at enhancing the anti-inflammatory response to modulate neuroinflammation in this disease. Full article

Neuroinflammation is a complex immune response triggered by brain injury or pathological stimuli, and is highly exacerbated in neurodegenerative diseases. It plays a dual role in the central nervous system, promoting repair in acute stages while aggravating disease progression by contributing to neuronal loss, synaptic dysfunction, and glial dysregulation in chronic phases. Inflammatory responses are mainly orchestrated by microglia and infiltrated monocytes, which, when dysregulated, not only harm existing neurons, but also impair the survival and differentiation of neural stem and progenitor cells in the affected brain regions. Modulating neuroinflammation is crucial for harnessing its protective functions while minimizing its detrimental effects. Current therapeutic strategies focus on fine-tuning inflammatory responses through pharmacological agents, bioactive molecules, and stem cell-based therapies. These approaches aim to restore immune homeostasis, support neuroprotection, and promote regeneration in various neurological disorders. However, animal models sometimes fail to reproduce human-specific inflammatory responses in the brain. In this context, stem-cell-derived models provide a powerful tool to study neuroinflammatory mechanisms in a patient-specific and physiologically relevant context. These models facilitate high-throughput screening, personalized medicine, and the development of targeted therapies while addressing the limitations of traditional animal models, paving the way for more targeted and effective treatments. Full article

Mental illnesses can have a significant impact on individuals experiencing acute coronary syndromes (ACS). Mental illnesses are associated with an increased cardiovascular risk profile and early onset of cardiovascular disease. A critical aspect of this interplay is the effect of psychiatric conditions on left ventricular ejection fraction (LVEF), a key parameter in evaluating cardiac function and predicting long-term outcomes in ACS patients. The present single-center, retrospective study investigated the associations between psychiatric conditions and cardiac function, with a focus on LVEF in ACS patients. The inclusion criteria were Italian nationality and 30 years or older. One hundred and sixty-four patients without (M_age = 68.8 ± 10.6, 62 females) and 161 patients with a psychiatric diagnosis (M_age = 68.4 ± 13.7, 63 females) were enrolled. The data collected included sociodemographic variables, psychiatric diagnoses, LVEF, ACS type (STEMI/NSTEMI), smoking status, previous interventions, and pharmacological treatments. Statistical analyses included chi-square, t-tests, ANOVAs, and ANCOVA to assess differences across groups. Findings revealed lower LVEF in patients with a psychiatric diagnosis compared to patients without a psychiatric diagnosis (p = 0.004, d = 0.36). Patients without a psychiatric diagnosis were associated with NSTEMI (p = 0.047, φ = 0.11), hypertension (p = 0.003, φ = −0.16), and dyslipidemia (p = 0.022, φ = −0.13). In contrast, patients with a psychiatric diagnosis were associated with STEMI (p = 0.047, φ = 0.11), neurological dysfunction (p = 0.014, φ = 0.14), and chronic obstructive pulmonary disease (p = 0.010, φ = 0.14). Among psychiatric diagnoses, anxiety disorders were associated with lower LVEF compared to substance abuse disorders (p = 0.012, d = −0.81). The findings underscore the complex relationship between mental illness and cardiac function, emphasising the need to integrate psychiatric evaluations into cardiology care to optimise the management of both mental and cardiovascular health. This study has several limitations, including its design, which prevents causal conclusions, and the use of convenience sampling, which limits the generalizability of the findings. Full article

Background: The fimbria-fornix is a nerve fiber bundle that connects various structures of the limbic system in the brain and plays a key role in cognition. It has become a major target of deep brain stimulation (DBS) to treat memory impairment in both dementia patients and animal models of neurological diseases. Previously, we have reported the beneficial memory effects of chronic forniceal DBS in mouse models of intellectual disability disorders. In Rett syndrome and CDKL5 deficiency disorder models, DBS strengthens hippocampal synaptic plasticity, reduces dentate inhibitory transmission or increases adult hippocampal neurogenesis that aids memory. However, the underlying neuronal circuitry mechanisms remain unknown. This study we explored the neural network circuits involved in forniceal DBS treatment. Methods: We used acute forniceal DBS-induced expression of c-Fos, an activity-dependent neuronal marker, to map the brain structures functionally connected to the fornix. We also evaluated the mouse behavior of locomotion, anxiety, and fear memory after acute forniceal DBS treatment. Results: Acute forniceal DBS induces robust activation of multiple structures in the limbic system. DBS-induced neuronal activation extends beyond hippocampal formation and includes brain structures not directly innervated by the fornix. Conclusions: Acute forniceal DBS activates multiple limbic structures associated with emotion and memory. The neural circuits revealed here help elucidate the neural network effect and pave the way for further research on the mechanism by which forniceal DBS induces benefits on cognitive impairments. Full article