Search Results (965)

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

Stroke is a leading cause of morbidity and mortality worldwide, with ischemic stroke (IS) accounting for approximately 85% of cases. Recent research has highlighted the critical role of microRNAs (miRNAs), a class of small non-coding RNA molecules, in the pathogenesis of stroke. Among these, the miR-17-92 cluster and its paralogs have emerged as key regulators in the development of stroke pathology and the subsequent recovery processes. We emphasize their regulatory roles in key pathological processes, including inflammation, apoptosis, neuroprotection, and tissue repair. We provide an overview of these mechanisms to support the identification of novel miRNA-based therapeutic targets and to improve stroke diagnosis, treatment, and recovery strategies. Specific miRNAs, such as miR-19a, miR-18a, and miR-92a, contribute to processes including neurogenesis, axonal growth, and a reduction in neuronal apoptosis. The miR-17-92 cluster also offers potential therapeutic applications by targeting injury-induced pathways, such as modulating apoptosis, promoting axonal elongation, or inhibiting neurodegeneration. Preclinical studies have suggested their potential to enhance neural regeneration and promote functional recovery. Future research should further elucidate the regulatory mechanisms of the miR-17-92 members and their therapeutic potential to enhance stroke treatment strategies. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke patients with ataxic symptoms, to follow up on changes in motor function and balance due to recovery and rehabilitation, and to investigate the different effects of two treatment methods on neuronal plasticity. Methods: Therefore, fMRI-paradigms foot tapping and the motor imagery (MI) of a balancing task (tandem walking) were employed. Results: The paradigms investigated were suitable for ataxic stroke patients to monitor changes in neuroplasticity while revealing increased activity in the primary motor cortex (M1) and the cerebellum over 3 months of treatment. Furthermore, analysis of the more complex balance task revealed augmented activation of association areas due to training. Coordination exercises, constituting a specific treatment of ataxic symptoms, indicate more consolidated brain activations, corresponding to a faster motor learning process. Activation within Brodmann Area 7 has been prominent among all paradigms, indicating a special importance of this region for coordinative functions. Conclusions: Further studies are needed to confirm our results in larger patient groups. Clinical Trial Registration: German Clinical Trials Registry (drks.de). Identifier: DRKS00020825. Registered 16.07.2020. Full article

Background and Objectives: Endovascular treatment (EVT) has been shown to enhance long-term recovery and lower mortality rates in patients with intracranial large vessel occlusion-associated acute ischemic strokes (AISs).We aimed to evaluate the predictive value of the pre-stroke CHA₂DS₂-VA, R₂CHA₂DS₂-VA, CHA₂DS₂-VASc, and R₂CHA₂DS₂-VASc scores in determining 90-day functional outcomes based on the modified Rankin Scale (mRS). Methods: In a single center between 2018 and 2023, 665 AIS patients who underwent EVT and achieved successful reperfusion were screened retrospectively. After inclusion and exclusion criteria, 583 patients were included. Based on 90-day mRS scores, patients were classified into two groups: good (mRS ≤ 2, n = 257) and poor functional outcomes (mRS 3–6, n = 326). The pre-stroke scores were calculated. Results: When ROC curve analysis was performed, R₂CHA₂DS₂-VA demonstrated the highest AUC value (p = 0.0443) among these scores. The optimal cutoff score was determined to be 4, yielding a sensitivity of 75.77% and specificity of 93.39%. In multivariable analysis, a higher R₂CHA₂DS₂-VA score was significantly associated with worse outcomes (OR = 1.637, 95%, CI: 2.436–5.510, p < 0.001). A longer onset-to-recanalization time (OR = 1.009, 95%, CI: 1.005–1.014, p < 0.001) and presence of hyperlipidemia (OR = 2.960, 95%, CI: 1.254–6.988, p = 0.01) were correlated with poor prognosis. Higher baseline NIHSS scores were associated with unfavorable outcomes (OR = 1.201, 95%, CI: 1.014–1.422, p = 0.034), and this association remained significant for NIHSS scores measured 24 h post-EVT (OR = 1.467, 95%, CI: 1.230–1.748, p < 0.001). Conclusions: The R₂CHA₂DS₂-VA score demonstrates superior predictive ability for 90-day functional outcomes in AIS patients treated with EVT, surpassing CHA₂DS₂-VASc and similar scoring systems. Full article

Oral administration of dipyridamole (DIP) with acetylsalicylic acid (ACA) is recommended in thromboembolic conditions or for the treatment of myocardial infarction and stroke. The present study presents an alternative dosage form of these two active ingredients, consisting of a honey core and a dark chocolate coating. The composition masks the bitter taste, is palatable and ensures compliance of a wide range of patients, mainly pediatric. For the simultaneous quantitative determination of the analytes, a Diode Array Detector/Fluorescence Detector (HPLC-DAD/FLD) method was used with a C18 column (250 mm × 4.6 mm, 5 μm) and an isocratic two-phase system (A: H₂O 0.2% formic acid—B: Acetonitrile-H₂O 90:10 v/v) 65:35 v/v. The method was validated according to ICH guidelines (r² > 0.999, RSD < 2.3%, % Recovery > 95.4%), and a stability study of the two active ingredients as well as salicylic acid (SAL), which is a hydrolysis product of ACA, was followed. Finally, a digestion protocol (oral cavity–stomach–intestine) for edible materials was applied to determine the release rate of ACA, DIP and SAL in the gastrointestinal tract, while an in vitro permeability study (P_app) was subsequently performed in Franz cells. The results show satisfactory behavior of ACA and DIP and provide a trigger for further studies of the formulation. Full article

Background: Bilateral movement training (BMT) and interlimb coupling have emerged as promising neurophysiologically-based rehabilitation approaches for stroke survivors. However, the underlying mechanisms and optimal implementation strategies remain incompletely understood. This systematic review explored the neurophysiological principles underlying BMT and interlimb coupling interventions that led to positive clinical post-stroke rehabilitation outcomes, focusing on identifying the most effective bilateral and interlimb movement strategies. Methods: A 10-year literature search (2014–2024) following PRISMA guidelines was conducted across PubMed, Cochrane, and Google Scholar databases using keywords including stroke rehabilitation, bilateral movement training, cross-education, interlimb coupling, and interlimb transfer. Studies were included if they involved human subjects, clinical trials, stroke survivors, and described bilateral training protocols. Data extraction focused on neurophysiological mechanisms, intervention characteristics, and clinical outcomes. Quality assessment was performed using validated methodological appraisal tools, including the Newcastle-Ottawa Scale and Cochrane RoB 2.0. Results: Of 199 initially identified studies, 28 met inclusion criteria for detailed analysis. BMT demonstrated effectiveness in enhancing motor recovery by engaging neurophysiological mechanisms, including central pattern generators, interhemispheric coupling, and cortical disinhibition. High-intensity BMT provided significant gains for individuals with moderate to severe impairments, while low-intensity training benefited early recovery stages. Interventions incorporating task-specific exercises, robotic assistance, sensory enhancement, and virtual reality showed particular promise for addressing motor recovery complexities. However, significant research gaps were identified, including limited understanding of individualized responses to BMT, insufficient research on combined upper and lower limb training, and minimal integration of advanced technologies. Conclusions: BMT and interlimb coupling play critical roles in post-stroke rehabilitation by facilitating neural plasticity and interlimb coordination. Integrating robotic assistance, sensory enhancement, and virtual reality with BMT offers a robust framework for maximizing rehabilitation outcomes. Future research should prioritize longitudinal studies, personalized rehabilitation approaches, technology integration, and stratified interventions tailored to individual needs to optimize neuroplasticity and enhance quality of life for stroke survivors. Full article

Background/Objectives: Individuals with chronic stroke often experience various impairments, including poor balance, reduced mobility, limited physical activity, and difficulty performing daily tasks. In the context of the COVID-19 pandemic, telerehabilitation (TR) can overcome the barriers of geographical and physical distancing, time, costs, and travel, as well as the anxiety about contracting COVID-19. In this retrospective case-control study, we aim to evaluate the motor and cognitive effects of balance TR training carried out with a sensor-based non-immersive virtual reality system compared to conventional rehabilitation in chronic stroke patients. Methods: Twenty chronic post-stroke patients underwent evaluation for inclusion in the analysis through an electronic recovery data system. The patients included in the study were divided into two groups with similar medical characteristics and duration of rehabilitation training. However, the groups differed in the type of rehabilitation approach used. The experimental group (EG) received TR with a sensor-based VR device, called VRRS—HomeKit (n. 10). In contrast, the control group (CG) underwent conventional home-based rehabilitation (n. 10). Results: At the end of the training, we observed significant improvements in the EG in the 10-m walking test (10MWT) (p = 0.01), Timed-Up-Go Left (TUG L) (p = 0.01), and Montreal Cognitive Assessment (MoCA) (p = 0.005). Conclusions: In our study, we highlighted the potential role of sensor-based virtual reality TR in chronic stroke patients for improving lower limb function, suggesting that this approach is feasible and not inferior to conventional home-based rehabilitation. Full article

Background and Objectives: Stroke units rely on interdisciplinary teams. Professionals with complementary alternative practices may join the team since such approaches are increasingly supporting the stroke recovery process. The aim of this study was to develop a better understanding of how a dance and somatic-informed movement intervention could be utilized in an inpatient setting as an adjunct to post-stroke therapy. We sought to identify (1) what knowledge we could draw on to develop the content and pedagogy for the intervention, (2) what helped/hindered the intervention aimed at functional recovery, as perceived by the practitioner-researchers, and (3) the relationships experienced with the various stakeholders. Materials and Methods: This exploratory qualitative study used the enhanced critical incident technique to collect retrospective self-report data from two practitioner-researchers engaged in delivering the intervention over two months. The data underwent thematic analysis. Patients (n = 6) in a stroke unit were selected within ≤72 h of hospital admission. The intervention was conducted four to six times a week until the vascular neurologist (co-researcher) authorized their transfer to a rehabilitation hospital. Results: The intervention evolved from crafting content and pedagogy at the intersection of different areas of knowledge (dance, somatics, neuroscience, and stroke). It was based on active, assisted, and passive movements. Verbal, tactile, visual, and imaginary inputs used to enhance body awareness were perceived as potentially helping patients recover some range of motion, quality of movements, and voluntary movement control, and fostering calmness and motivation. The intervention was well received by stakeholders. Conclusions: Dance and somatic-informed movement can be a complementary therapy in stroke units, although it requires a delicate juggling of time allocation within the interdisciplinary team. Further studies should be conducted with a larger number of patients and different practitioners. Collaboration between qualitative and quantitative researchers is needed to make a robust case for such interventions. Full article

Ischemic stroke (IS) is a high-mortality, multi-complication cardiovascular disease. Reducing brain injury and promoting neuronal repair after IS onset remain important challenges for current treatments. Our team previously found that PAS840, an extract from Periplaneta americana (L.), protects nerve function; this study further uses LC-MS/MS and peptidomics to analyze PAS840’s components and network pharmacology to predict its ischemic stroke (IS) therapeutic targets. We then employed Transwell, a biochemical kit, real-time quantitative polymerase chain reaction (RT-qPCR), and transcriptomics to investigate PAS840’s effects on migration ability, oxidative stress levels, and cellular pathways in mouse microglial cells (BV-2) following oxygen–glucose deprivation/reoxygenation (OGD/R) injury. Finally, using Evans blue staining, immunohistochemical analysis, and RT-qPCR, we investigated PAS840’s effects on the blood–brain barrier, inflammation pathways, and neural function in a transient middle cerebral artery occlusion (tMCAO) rat model. PAS840 components target multiple IS pathways, effectively inhibit NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway activation in BV-2 cells following OGD/R, reduce cellular oxidative stress, inflammation, and pyroptosis, and improve cell viability and migration ability. PAS840 decreases NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway expression in tMCAO rat brains, reduces inflammation, activates BDNF/VGF/NGR1/Erbb4 neurotrophic factor and vascular endothelial growth factor pathways, enhances neuronal cell viability, and effectively protects and repairs the blood–brain barrier. Full article

Background and Objectives: Brain-computer interface (BCI) technology is revolutionizing stroke rehabilitation by offering innovative neuroengineering solutions to address neurological deficits. By bypassing peripheral nerves and muscles, BCIs enable individuals with severe motor impairments to communicate their intentions directly through control signals derived from brain activity, opening new pathways for recovery and improving the quality of life. The aim of this study was to explore the beneficial effects of BCI system-based interventions on upper limb motor function and performance of activities of daily living (ADL) in stroke patients. We hypothesized that integrating BCI into occupational therapy would result in measurable improvements in hand strength, dexterity, independence in daily activities, and cognitive function compared to baseline. Materials and Methods: An observational study was conducted on 56 patients with subacute stroke. All patients received standard medical care and rehabilitation for 54 days, as part of the comprehensive treatment protocol. Patients underwent BCI training 2–3 times a week instead of some occupational therapy sessions, with each patient completing 15 sessions of BCI-based recoveriX treatment during rehabilitation. The occupational therapy program included bilateral exercises, grip-strengthening activities, fine motor/coordination tasks, tactile discrimination exercises, proprioceptive training, and mirror therapy to enhance motor recovery through visual feedback. Participants received ADL-related training aimed at improving their functional independence in everyday activities. Routine occupational therapy was provided five times a week for 50 min per session. Upper extremity function was evaluated using the Box and Block Test (BBT), Nine-Hole Peg Test (9HPT), and dynamometry to assess gross manual dexterity, fine motor skills, and grip strength. Independence in daily living was assessed using the Functional Independence Measure (FIM). Results: Statistically significant improvements were observed across all the outcome measures (p < 0.001). The strength of the stroke-affected hand improved from 5.0 kg to 6.7 kg, and that of the unaffected hand improved from 29.7 kg to 40.0 kg. Functional independence increased notably, with the FIM scores rising from 43.0 to 83.5. Cognitive function also improved, with MMSE scores increasing from 22.0 to 26.0. The effect sizes ranged from moderate to large, indicating clinically meaningful benefits. Conclusions: This study suggests that BCI-based occupational therapy interventions effectively improve upper extremity motor function and daily functions and have a positive impact on the cognition of patients with subacute stroke. Full article

EMG-derived muscle synergy, as a representation of neuromotor modules utilized for motor control, has been proposed as a biomarker for stroke rehabilitation. Here, we evaluate the utility of muscle synergies for assessing motor function and predicting post-intervention motor outcome in a stroke rehabilitation clinical trial. Subacute stroke survivors (n = 59) received month-long acupuncture (Acu), sham acupuncture (ShamAcu) or no acupuncture (NoAcu) as adjunctive rehabilitative intervention alongside standard physiotherapy. Clinical scores and EMGs (14 muscles, eight motor tasks) were collected from the stroke-affected upper limb before and after intervention. We then extracted muscle synergies from EMGs using non-negative matrix factorization and designed 12 muscle synergy indices (MSIs) to summarize different aspects of post-stroke synergy features. All MSIs correlated with multiple clinical scores, suggesting that our indices could potentially serve as biomarkers for post-stroke motor functional assessments. While the intervention groups did not differ in their pre-to-post differences in the clinical scores, the inclusion of MSIs into analysis revealed that on average Acu promoted more recovery of synergy features than ShamAcu and NoAcu, though not all subjects in the group were Acu responders. We then built regression models using pre-intervention MSIs and clinical variables to predict the outcomes of Acu and NoAcu and showed by a preliminary retrospective simulation of patient stratification that MSI-based predictions could have led to better post-intervention motor improvement. Overall, we demonstrate that muscle synergies can potentially clarify the effects of interventions and assist in motor assessment, outcome prediction, and treatment selection. 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: Post-stroke aphasia (PSA) severely limits communication and quality of life. This case study explores the impact of an integrated Neurologic Music Therapy (NMT) approach, combining Melodic Intonation Therapy (MIT) and Therapeutic Singing (TS), on language recovery and brain reorganization in a 59-year-old woman with non-fluent motor aphasia following an ischemic stroke. Methods: Over 8 weeks, the patient underwent 24 sessions of MIT alongside standard speech therapy. Language abilities were assessed using the Western Aphasia Battery-Revised, while fMRI scans captured neurophysiological changes pre- and post-intervention. Results: The results showed significant language improvements: spontaneous speech increased by 68.9%, auditory comprehension by 30.8%, and naming by 83.3%. The Aphasia Quotient rose from 39.3 to 61.4, marking a shift from severe to moderate aphasia. Neuroimaging revealed heightened activation in both hemispheres, especially in the superior frontal and parietal regions, supplementary motor area, and superior temporal gyrus. Increased engagement of the limbic system, particularly the paracingulate gyrus, pointed to emotional involvement and widespread cortical reorganization. Conclusions: These findings highlight the effectiveness of integrating MIT and TS with emotionally meaningful music, supporting language recovery and neural plasticity in PSA. Full article