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In the penumbra of a brain infarct, neurons initially remain structurally intact, but perfusion is insufficient to maintain neuronal activity at physiological levels. Improving neuronal recovery in the penumbra has large potential to advance recovery of stroke patients, but penumbral pathology is incompletely understood, and treatments are scarce. We hypothesize that low activity in the penumbra is associated with apoptosis and thus contributes to irreversible neuronal damage. We explored the putative relationship between low neuronal activity and apoptosis in cultured neurons exposed to variable durations of hypoxia or TTX. We combined electrophysiology and live apoptosis staining in 42 cultures, and compared effects of hypoxia and TTX silencing in terms of network activity and apoptosis. Hypoxia rapidly reduced network activity, but cultures showed limited apoptosis during the first 12 h. After 24 h, widespread apoptosis had occurred. This was associated with full activity recovery observed upon reoxygenation within 12 h, but not after 24 h. Similarly, TTX exposure strongly reduced activity, with full recovery upon washout within 12 h, but not after 24 h. Mean temporal evolution of apoptosis in TTX-treated cultures was the same as in hypoxic cultures. These results suggest that prolonged low activity may be a common factor in the pathways towards apoptosis.

Ischemic stroke is a leading cause of mortality and chronic disability. Either recovery or progression towards irreversible failure of neurons and astrocytes occurs within minutes to days, depending on remaining perfusion levels. Initial damage arises from energy depletion resulting in a failure to maintain homeostasis and ion gradients between extra- and intracellular spaces. Astrocytes play a key role in these processes and are thus central players in the dynamics towards recovery or progression of stroke-induced brain damage. Here, we present a synopsis of the pivotal functions of astrocytes at the tripartite synapse, which form the basis of physiological brain functioning. We summarize the evidence of astrocytic failure and its consequences under ischemic conditions. Special emphasis is put on the homeostasis and stroke-induced dysregulation of the major monovalent ions, namely Na + , K + , H + , and Cl - , and their involvement in maintenance of cellular volume and generation of cerebral edema.

Despite recent advances in treatment options, stroke remains a highly prevalent and devastating condition with significant socioeconomic impact. Recanalization therapies, including intravenous thrombolysis and endovascular treatments, have revolutionized stroke management and prognosis, providing a promising framework for exploring new therapeutic strategies. Endothelial dysfunction plays a critical role in the pathophysiology, progression, and prognosis of stroke. This review aims to synthesize the current evidence regarding the involvement of the nitric oxide (NO)/endothelium pathway in ischemic stroke, with a particular focus on aging, response to recanalization therapies, and therapeutic approaches. While significant progress has been made in recent years in understanding the relationship between endothelial dysfunction and stroke, many uncertainties persist, and although treatments targeting this pathway are promising, they have yet to demonstrate clear clinical benefits. [ABSTRACT FROM AUTHOR]

This study explores the neuroprotective effects of neuropeptide FF (NPFF, FLFQPQRFamide) in the context of ischemic injury. Based on transcriptomic analysis in stroke models treated with 5-Aza-dC and task-specific training, we identified significant gene expression changes, particularly involving NPFF. To further explore NPFF's role in promoting neuronal recovery, recombinant NPFF protein (rNPFF) was used in primary mixed cortical cultures subjected to oxygen-glucose deprivation and reoxygenation. Our results demonstrated that rNPFF significantly reduced lactate dehydrogenase release, indicating decreased cellular damage. It also significantly increased the expression of TUJ1 and MAP2, markers of neuronal survival and dendritic integrity. Additionally, rNPFF significantly upregulated key synaptic proteins, including GAP43, PSD95, and synaptophysin, which are essential for synaptic repair and plasticity. Post-injury rNPFF treatment led to a significant upregulation of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, which play critical roles in neuronal survival, growth, and synaptic plasticity. Moreover, rNPFF activated the protein kinase Cε isoform, Sirtuin 1, and peroxisome proliferator-activated receptor gamma pathways, which are crucial for regulating cellular stress responses, synaptic plasticity, and energy homeostasis, further promoting neuronal survival and recovery. These findings suggest that rNPFF may play a pivotal role in enhancing neuronal survival and synaptic plasticity after ischemic injury, highlighting its potential as a therapeutic target for stroke recovery. [ABSTRACT FROM AUTHOR]

Background/Objectives: Posterior circulation stroke (PCS) poses a diagnostic challenge due to the diverse and subtle clinical manifestations. While the FAST (Face, Arms, Speech, Time) mnemonic has proven effective in identifying anterior circulation stroke, its sensitivity to posterior events is less clear. Recently, the addition of Balance and Eyes to the mnemonic has been proposed as a more comprehensive tool for stroke recognition. Despite this, evidence directly comparing the effectiveness of BE-FAST and FAST in identifying PCS remains limited. Methods: A retrospective analysis was performed on stroke calls at a comprehensive stroke centre, Sydney, Australia. BE-FAST symptoms first assessed at an emergency department triage were recorded, along with automated acute computerised tomography perfusion (CTP) imaging findings. Haemorrhagic strokes were excluded from analysis. An ischaemic stroke diagnosis was confirmed 48–72 h later with magnetic resonance imaging (MRI) brain. The performance of 1. BE-FAST and FAST and 2. BE-FAST and CTP in the hyperacute detection of posterior circulation ischaemic stroke was compared. Results: Out of 164 identified ischaemic infarcts confirmed on MRIs, 46 were PCS. Of these, 27 were FAST-positive, while 45 were BE-FAST-positive. Overall, BE-FAST demonstrated a higher sensitivity compared to FAST in identifying PCS (97.8 vs. 58.7) but suffered from a lower specificity (10.0 vs. 39.8). Notably, 39.1% (n = 18) of patients with PCS would have been missed if only FAST were used. Furthermore, of the 26 PCS negative on CTP, 25 were BE-FAST-positive, and 14 were FAST-positive. Conclusions: The incorporation of Balance and Eye assessments into the FAST protocol improves PCS detection, although may yield more false positives. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the use of image-guided volumetry in cerebellar infarction during the decision-making process for surgery. Particular emphasis was placed on the ratio of the infarction volume to the cerebellar volume or cranial posterior fossa volume. Methods: A retrospective, multicenter, multidisciplinary study design was selected. Statistical methods such as regression analysis and ROC analysis included the volumetric data of the infarction, the posterior fossa and the cerebellum itself as new factors. Results: Thirty-eight patients (mean age 75 (SD: 13.93) years, 16 (42%) female patients) were included. The mean infarction volume was 37.79 (SD: 25.24) cm3. Patients treated surgically had a 2.05-fold larger infarction than those managed without surgery (p ≤ 0.001). Medical and surgical treatment revealed a significant difference in the ratio of the cranial posterior fossa volume to the infarction volume (medical 12.05, SD:9.09; surgical 5.14, SD: 5,65; p ≤ 0.001) and the ratio of the cerebellar volume to the infarction volume (medical 8.55, SD: 5.97; surgical 3.82, SD: 3.39; p ≤ 0.001). Subsequent multivariate regression analysis for surgical therapy showed significant results only for the posterior fossa volume to infarction volume ratio ≤/> 4:1 (OR: 1.162, CI: 1.007–1.341, p = 0.04). Younger (≤60 years) patients also had a significantly better outcome at discharge (p ≤ 0.017). A cut-off value for the infarction volume of 31.35 cm3 (sensitivity = 0.875, specificity = 0.2) was determined for the necessity of surgery. Conclusions: Volumetric data on the infarction, the posterior fossa and the cerebellum itself could be meaningful in decision-making towards surgery. [ABSTRACT FROM AUTHOR]

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart–brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments. [ABSTRACT FROM AUTHOR]

The electroencephalogram (EEG) is a cornerstone tool for the diagnosis, management, and prognosis of selected patient populations. EEGs offer significant advantages such as high temporal resolution, real-time cortical function assessment, and bedside usability. The quantitative EEG (qEEG) added the possibility of long recordings being processed in a compressive manner, making EEG revision more efficient for experienced users, and more friendly for new ones. Recent advancements in commercially available software, such as Persyst, have significantly expanded and facilitated the use of qEEGs, marking the beginning of a new era in its application. As a result, there has been a notable increase in the practical, real-world utilization of qEEGs in recent years. This paper aims to provide an overview of the current applications of qEEGs in daily neurological emergencies and ICU practice, and some elementary principles of qEEGs using Persyst software in clinical settings. This article illustrates basic qEEG patterns encountered in critical care and adopts the new terminology proposed for spectrogram reporting. [ABSTRACT FROM AUTHOR]

S100 calcium-binding protein B (S100B) is a protein primarily known as a biomarker for central nervous system (CNS) injuries, reflecting blood–brain barrier (BBB) permeability and dysfunction. Recently, S100B has also been implicated in cardiovascular diseases, including heart failure (HF). Thus, we investigated serum levels of S100B in 146 chronic HF patients from the Cognition.Matters-HF study and their association with cardiac and cognitive dysfunction. The median S100B level was 33 pg/mL (IQR: 22–47 pg/mL). Higher S100B levels were linked to longer HF duration (p = 0.014) and increased left atrial volume index (p = 0.041), but also with a higher prevalence of mild cognitive impairment (p = 0.023) and lower visual/verbal memory scores (p = 0.006). In a multivariable model, NT-proBNP levels independently predicted S100B (T-value = 2.27, p = 0.026). S100B did not impact mortality (univariable HR (95% CI) 1.00 (0.99–1.01); p = 0.517; multivariable HR (95% CI) 1.01 (1.00–1.03); p = 0.142), likely due to its reflection of acute injury rather than long-term outcomes and the mild HF phenotype in our cohort. These findings underscore S100B's value in comprehensive disease assessment, reflecting both cardiac dysfunction and potentially related BBB disruption. [ABSTRACT FROM AUTHOR]

Upper limb weakness following stroke poses a significant global psychosocial and economic burden. Non-invasive brain stimulation (NIBS) is a potential adjunctive treatment in rehabilitation. However, traditional approaches to rebalance interhemispheric inhibition may not be effective for all patients. The supportive role of the contralesional hemisphere in recovery of upper limb motor function has been supported by animal and clinical studies, particularly for those with severe strokes. This review aims to provide an overview of the facilitation role of the contralesional hemisphere for post-stroke motor recovery. While more studies are required to predict responses and inform the choice of NIBS approach, contralesional facilitation may offer new hope for patients in whom traditional rehabilitation and NIBS approaches have failed. [ABSTRACT FROM AUTHOR]

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic–ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies. [ABSTRACT FROM AUTHOR]

Background: The association between arterial stiffness and outcome after endovascular treatment (EVT) is unknown. This study investigated whether arterial stiffness predicts post-EVT outcome in patients with acute ischemic stroke. Methods: This retrospective and observational cohort study included consecutive patients treated with EVT for acute ischemic stroke from June 2020 to November 2022. Arterial stiffness was assessed by brachial–ankle pulse wave velocity. Poor functional outcome was defined as a modified Rankin Scale score ≥3 at 3 months. Results: The mean age of patients included in this study was 71.9 ± 11.8 years, and 57.3% were men. Poor functional outcome was present in 46.8%. Multivariable logistic regression analysis showed that arterial stiffness was independently associated with poor functional outcome (odds ratio 8.640, 95% confidence interval [CI] 1.581–47.228) after adjusting for age, initial stroke severity, hypertension, atrial fibrillation, device pass number, and successful recanalization. A nomogram based on the multivariable statistic model showed a better prediction of poor functional outcome compared to classic risk factor models without arterial stiffness (net reclassification improvement 0.529, 95% CI 0.186–0.873; integrated discrimination improvement 0.046, 95% CI 0.009–0.083). Conclusions: We found that arterial stiffness was an independent predictor of poor functional outcome in patients treated with EVT following acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Despite the increased use of mechanical thrombectomy (MT) in recent years, there remains a lack of research on in-hospital mortality rates following the procedure, the primary factors influencing these rates, and the potential for predicting them. This study aimed to utilize interpretable machine learning (ML) to help clarify these uncertainties. Methods: This retrospective study involved patients with anterior circulation large vessel occlusion (LVO)-related ischemic stroke who underwent MT. The patient division was made into two groups: (I) the in-hospital death group, referred to as miserable outcome, and (II) the in-hospital survival group, or favorable outcome. Python 3.10.9 was utilized to develop the machine learning models, which consisted of two types based on input features: (I) the Pre-MT model, incorporating baseline features, and (II) the Post-MT model, which included both baseline and MT-related features. After a feature selection process, the models were trained, internally evaluated, and tested, after which interpretation frameworks were employed to clarify the decision-making processes. Results: This study included 602 patients with a median age of 76 years (interquartile range (IQR) 65–83), out of which 54% (n = 328) were female, and 22% (n = 133) had miserable outcomes. Selected baseline features were age, baseline National Institutes of Health Stroke Scale (NIHSS) value, neutrophil-to-lymphocyte ratio (NLR), international normalized ratio (INR), the type of the affected vessel ('Vessel type'), peripheral arterial disease (PAD), baseline glycemia, and premorbid modified Rankin scale (pre-mRS). The highest odds ratio of 4.504 was observed with the presence of peripheral arterial disease (95% confidence interval (CI), 2.120–9.569). The Pre-MT model achieved an area under the curve (AUC) value of around 79% utilizing these features, and the interpretable framework discovered the baseline NIHSS value as the most influential factor. In the second data set, selected features were the same, excluding pre-mRS and including puncture-to-procedure-end time (PET) and onset-to-puncture time (OPT). The AUC value of the Post-MT model was around 84% with age being the highest-ranked feature. Conclusions: This study demonstrates the moderate to strong effectiveness of interpretable machine learning models in predicting in-hospital mortality following mechanical thrombectomy for ischemic stroke, with AUCs of 0.792 for the Pre-MT model and 0.837 for the Post-MT model. Key predictors included patient age, baseline NIHSS, NLR, INR, occluded vessel type, PAD, baseline glycemia, pre-mRS, PET, and OPT. These findings provide valuable insights into risk factors and could improve post-procedural patient management. [ABSTRACT FROM AUTHOR]

Post-stroke cognitive impairment is a common and disabling condition with few effective therapeutic options. After stroke, neural reorganization and other neuroplastic processes occur in response to ischemic injury, which can result in clinical improvement through spontaneous recovery. Neuromodulation through transcranial direct current stimulation (tDCS) is a promising intervention to augment underlying neuroplasticity in order to improve cognitive function. This form of neuromodulation leverages mechanisms of neuroplasticity post-stroke to optimize neural reorganization and improve function. In this review, we summarize the current state of cognitive neurorehabilitation post-stroke, the practical features of tDCS, its uses in stroke-related cognitive impairment across cognitive domains, and special considerations for the use of tDCS in the post-stroke patient population. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke (AIS) and traumatic brain injury (TBI) are two severe neurological events, both being major causes of death and prolonged impairment. Their incidence continues to rise due to the global increase in the number of people at risk, representing a significant burden on those remaining impaired, their families, and society. These molecular and cellular mechanisms of both stroke and TBI present similarities that can be targeted by treatments with a multimodal mode of action, such as traditional Chinese medicine. Therefore, we performed a detailed review of the preclinical and clinical development of MLC901 (NeuroAiDTMII), a natural multi-herbal formulation targeting several biological pathways at the origin of the clinical deficits. The endogenous neurobiological processes of self-repair initiated by the brain in response to the onset of brain injury are often insufficient to achieve complete recovery of impaired functions. This review of MLC901 and its parent formulation MLC601 confirms that it amplifies the natural self-repair process of brain tissue after AIS or TBI. Following AIS and TBI where "time is brain", many patients enter the post-acute phase with their functions still impaired, a period when "the brain needs time to repair itself". The treatment goal must be to accelerate recovery as much as possible. MLC901/601 demonstrated a significant reduction by 18 months of recovery time compared to a placebo, indicating strong potential for facilitating the improvement of health outcomes and the more efficient use of healthcare resources. [ABSTRACT FROM AUTHOR]

Seizures should be diagnosed and treated to ensure optimal health outcomes in critically ill patients admitted in the medical intensive care unit (MICU). Continuous electroencephalography is still infrequently used in the MICU. We investigated the effectiveness of routine EEG (rEEG) in detecting seizures in the MICU. A total of 560 patients admitted to the MICU between October 2018 and March 2023 and who underwent rEEG were reviewed. Seizure-related rEEG constituted 47% of all rEEG studies. Totally, 39% of the patients experienced clinical seizures during hospitalization; among them, 48% experienced the seizure, and 13% experienced their first seizure after undergoing an rEEG study. Seventy-seven percent of the patients had unfavorable short-term outcomes. Patients with cardiovascular diseases were the most likely to have the suppression/burst suppression (SBS) EEG pattern and the highest mortality rate. The rhythmic and periodic patterns (RPPs) and electrographic seizure (ESz) EEG pattern were associated with seizures within 24 h after rEEG, which was also related to unfavorable outcomes. Significant predictors of death were age > 59 years, the male gender, the presence of cardiovascular disease, a Glasgow Coma Scale score ≤ 5, and the SBS EEG pattern, with a predictive performance of 0.737 for death. rEEG can help identify patients at higher risk of seizures. We recommend repeated rEEG in patients with ESz or RPP EEG patterns to enable a more effective monitoring of seizure activities. [ABSTRACT FROM AUTHOR]

Migraine is a highly prevalent brain condition with paroxysmal changes in brain excitability believed to contribute to the initiation of an attack. The attacks and their unpredictability have a major impact on the lives of patients. Clinical management is hampered by a lack of reliable predictors for upcoming attacks, which may help in understanding pathophysiological mechanisms to identify new treatment targets that may be positioned between the acute and preventive possibilities that are currently available. So far, a large range of studies using conventional hospital-based EEG recordings have provided contradictory results, with indications of both cortical hyper- as well as hypo-excitability. These heterogeneous findings may largely be because most studies were cross-sectional in design, providing only a snapshot in time of a patient's brain state without capturing day-to-day fluctuations. The scope of this narrative review is to (i) reflect on current knowledge on EEG changes in the context of migraine, the attack cycle, and underlying pathophysiology; (ii) consider the effects of migraine treatment on EEG features; (iii) outline challenges and opportunities in using EEG for monitoring attack susceptibility; and (iv) discuss future applications of EEG in home-based settings. [ABSTRACT FROM AUTHOR]

Stroke constitutes a significant global cause of mortality and disability. The implementation of stroke units influences hospital quality indicators, guiding care management. We aimed to compare hospital length of stay (LOS), in-hospital mortality, and post-discharge mortality between stroke patients admitted in the pre- and post-implementation periods of a stroke unit in a public hospital in southern Brazil. This retrospective cohort study used real-world data from one reference hospital, focusing on the intervention (stroke unit) and comparing it to the general ward (control). We analyzed the electronic medical records of 674 patients admitted from 2009 to 2012 in the general ward and 766 patients from 2013 to 2018 in the stroke unit. Admission to the stroke unit was associated with a 43% reduction in the likelihood of prolonged hospitalization. However, there was no significant difference in the risk of in-hospital mortality between the groups (Hazard ratio = 0.90; Interquartile range = 0.58 to 1.39). The incidence of death at three, six and twelve months post-discharge did not differ between the groups. Our study results indicate significant improvements in care processes for SU patients, including shorter LOS and better adherence to treatment protocols. However, our observations revealed no significant difference in mortality rates, either during hospitalization or after discharge, between the SU and GW groups. While SU implementation enhances efficiency in stroke care, further research is needed to explore long-term outcomes and optimize management strategies. [ABSTRACT FROM AUTHOR]

The management of blood pressure variability (BPV) in acute stroke presents a complex challenge with profound implications for patient outcomes. This narrative review examines the role of BPV across various stages of acute stroke care, highlighting its impact on treatment strategies and prognostic considerations. In the prehospital setting, while guidelines lack specific recommendations for BP management, emerging evidence suggests a potential link between BPV and outcomes. Among ischaemic stroke patients who are ineligible for reperfusion therapies, BPV independently influences functional outcomes, emphasising the need for individualised approaches to BP control. During intravenous thrombolysis and endovascular therapy, the intricate interplay between BP levels, recanalisation status, and BPV is evident. Striking a balance between aggressive BP lowering and avoiding hypoperfusion-related complications is essential. Intracerebral haemorrhage management is further complicated by BPV, which emerges as a predictor of mortality and disability, necessitating nuanced BP management strategies. Finally, among patients with acute subarachnoid haemorrhage, increased BPV may be correlated with a rebleeding risk and worse outcomes, emphasizing the need for BPV monitoring in this population. Integration of BPV assessment into clinical practice and research protocols is crucial for refining treatment strategies that are tailored to individual patient needs. Future studies should explore novel interventions targeting BPV modulation to optimise stroke care outcomes. [ABSTRACT FROM AUTHOR]

Background: Acute embolic ischemic stroke poses a significant healthcare challenge. Histological clot features' variability among patients with acute ischemic stroke treated by mechanical thrombectomy has potential implications for determining treatment and etiology. This study investigated the clot histological feature differences among patients who experienced cardioembolic stroke and embolic stroke of undetermined source with different left atrial appendage (LAA) morphologies. Methods: We conducted a prospective observational study involving 79 patients with acute embolic ischemic stroke undergoing mechanical thrombectomy. Computed tomography angiography images were used to classify LAA morphologies. An artificial intelligence algorithm assessed the clot fibrin and red blood cell contents. Results: Patients with chicken-wing LAA morphology exhibited lower mean clot fibrin proportions than did those with non-chicken-wing morphology (p < 0.001). Linear regression analysis showed that chicken-wing LAA was significantly associated with a lower clot fibrin proportion (estimate, −0.177; 95% CI [−0.259, −0.096]; p < 0.001). The successful recanalization rate and first-pass effect between the groups did not differ significantly. Conclusions: The chicken-wing LAA morphological type is associated with lower clot fibrin contents, suggesting potentially different embolism mechanisms or diverse embolic sources, compared with the non-chicken-wing LAA types. Further studies are required to investigate this association. [ABSTRACT FROM AUTHOR]

Anti-amyloid immunotherapies have recently emerged as treatments for Alzheimer's disease. While these therapies have demonstrated efficacy in clearing amyloid-β and slowing cognitive decline, they have also been associated with amyloid-related imaging abnormalities (ARIA) which include both edema (ARIA-E) and hemorrhage (ARIA-H). Given that ARIA have been associated with significant morbidity in cases of antithrombotic or thrombolytic therapy, an understanding of mechanisms of and risk factors for ARIA is of critical importance for stroke care. We discuss the latest data regarding mechanisms of ARIA, including the role of underlying cerebral amyloid angiopathy, and implications for ischemic stroke prevention and management. [ABSTRACT FROM AUTHOR]

The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital to the successful development of clinically useful medications. Stroke is generally accepted as the leading cause of adult disability globally and ischemic stroke accounts for the most common form of the two main stroke types. Despite its health and socioeconomic burden, there is still minimal availability of effective pharmacological therapies for its treatment. In this review, we take an in-depth look at the etiology and pathophysiology of ischemic stroke, including molecular and cellular changes. This is followed by a highlight of drugs, cellular therapies, and complementary medicines that are approved or undergoing clinical trials for the treatment and management of ischemic stroke. We also identify unexplored potential targets in stroke pathogenesis that can be exploited to increase the pool of effective anti-stroke and neuroprotective agents through de novo drug development and drug repurposing. [ABSTRACT FROM AUTHOR]

This study explored short- and mid-term functional outcomes in patients undergoing decompressive hemicraniectomy (DHC) due to space-occupying cerebral infarction and asked whether there is a potentially harmful effect of a priorly performed endovascular treatment (EVT). Medical records were screened for patients requiring DHC due to space-occupying cerebral infarction between January 2016 and July 2021. Functional outcomes at hospital discharge and at 3 months were assessed by the modified Rankin Scale (mRS). Out of 65 patients with DHC, 39 underwent EVT before DHC. Both groups, i.e., EVT + DHC and DHC alone, had similar volumes (280 ± 90 mL vs. 269 ± 73 mL, t-test, p = 0.633) and proportions of edema and infarction (22.1 ± 6.5% vs. 22.1 ± 6.1%, t-test, p = 0.989) before the surgical intervention. Patients undergoing EVT + DHC tended to have a better functional outcome at hospital discharge compared to DHC alone (mRS 4.8 ± 0.8 vs. 5.2 ± 0.7, Mann–Whitney-U, p = 0.061), while the functional outcome after 3 months was similar (mRS 4.6 ± 1.1 vs. 4.8 ± 0.9, Mann–Whitney-U, p = 0.352). In patients initially presenting with a relevant infarct demarcation (Alberta Stroke Program Early CT Score ≤ 5), the outcome was similar at hospital discharge and after 3 months between patients with EVT + DHC and DHC alone. This study provided no evidence for a harmful effect of EVT before DHC in patients with space-occupying brain infarction. [ABSTRACT FROM AUTHOR]

The article presents the latest data on pathological changes after cerebral ischemia caused by cardiac arrest. The data include amyloid accumulation, tau protein modification, neurodegenerative and cognitive changes, and gene and protein changes associated with Alzheimer's disease. We present the latest data on the dysregulation of genes related to the metabolism of the amyloid protein precursor, tau protein, autophagy, mitophagy, apoptosis, and amyloid and tau protein transport genes. We report that neuronal death after cerebral ischemia due to cardiac arrest may be dependent and independent of caspase. Moreover, neuronal death dependent on amyloid and modified tau protein has been demonstrated. Finally, the results clearly indicate that changes in the expression of the presented genes play an important role in acute and secondary brain damage and the development of post-ischemic brain neurodegeneration with the Alzheimer's disease phenotype. The data indicate that the above genes may be a potential therapeutic target for brain therapy after ischemia due to cardiac arrest. Overall, the studies show that the genes studied represent attractive targets for the development of new therapies to minimize ischemic brain injury and neurological dysfunction. Additionally, amyloid-related genes expression and tau protein gene modification after cerebral ischemia due to cardiac arrest are useful in identifying ischemic mechanisms associated with Alzheimer's disease. Cardiac arrest illustrates the progressive, time- and area-specific development of neuropathology in the brain with the expression of genes responsible for the processing of amyloid protein precursor and the occurrence of tau protein and symptoms of dementia such as those occurring in patients with Alzheimer's disease. By carefully examining the common genetic processes involved in these two diseases, these data may help unravel phenomena associated with the development of Alzheimer's disease and neurodegeneration after cerebral ischemia and may lead future research on Alzheimer's disease or cerebral ischemia in new directions. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) disruption of substrate degradation with pathogenic changes in lysosomal function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), and inflammatory process, and (3) progressive tissue/organ damage and cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current and future treatment, several potential treatments for MPS that can penetrate the blood–brain barrier and bone have been proposed and/or are in clinical trials, including targeting peptides and molecular Trojan horses such as monoclonal antibodies attached to enzymes via receptor-mediated transport. Gene therapy trials with AAV, ex vivo LV, and Sleeping Beauty transposon system for MPS are proposed and/or underway as innovative therapeutic options. In addition, possible immunomodulatory reagents that can suppress MPS symptoms have been summarized in this review. [ABSTRACT FROM AUTHOR]

Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug–drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an "abnormal" volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations. [ABSTRACT FROM AUTHOR]

Simple Summary: This survey is the first study assessing the semiology and treatment approach of the postictal phase in dogs with idiopathic epilepsy as well as its impact on the quality of life of both dogs and their owners. The postictal phase has been minimally studied in both human and veterinary medicine. This study aimed to understand postictal semiology, assess its impact on the quality of life, highlight its importance in managing seizure disorders, and explore potential therapeutic approaches for postictal symptom management. The outcomes of this research bring attention to the deficiencies in epilepsy treatment and indicate avenues for additional research that can enhance the quality of life. Background: Dogs with idiopathic epilepsy experience not only the preictal and ictal seizure phases but also the postictal phase. To date, research has primarily focused on the preictal and ictal semiology and therapeutic control of ictal events. Research into the postictal phase's pathophysiology, as a therapeutic target and how it impacts the quality of life, is sparse across different species. Interestingly, even if anecdotally, owners report the postictal period being an impactful negative factor on their quality of life as well as their dog's quality of life. Hypothesis/objectives: We aimed to assess the semiology and the impact of postictal signs on the quality of life of owners and dogs. Method: This observational study was carried out using surveys of owners of dogs with seizure disorders. Results: The questionnaire was filled out by 432 dog owners, 292 of whom provided complete responses that could be analysed. More than nine out of ten owners (97%) reported the presence of various postictal clinical signs. The dog's and the owner's quality of life was mainly affected by specific postictal signs, i.e., disorientation (dog: 31%; owner: 20%), compulsive walking (dog: 17%; owner: 22%), ataxia (dog: 12%; owner: 6%), and blindness (dog: 17%; owner: 10%). Nearly 61% of the owners felt that the severity of postictal signs was moderate or severe. Rescue antiseizure medications did not have an effect on controlling the postictal signs based on 71% of the responders. In contrast, 77% of the respondents reported that other measures such as rest, physical closeness, and a quiet and dark environment had a positive impact on the postictal phase. Conclusions and clinical importance: Overall, this survey shows that specific postictal signs are common and have a notable impact on the perceived quality of life of both dogs and their owners. According to the respondents, antiseizure medication might have no influence on the postictal phase in most cases, in contrast to other nonpharmacological measures. Further research on the management of the postictal phase is vital for improving the quality of life of dogs with seizure disorders and their owners. [ABSTRACT FROM AUTHOR]

Following a stroke, the emergence of amygdala-related disorders poses a significant challenge, with severe implications for post-stroke mental health, including conditions such as anxiety and depression. These disorders not only hinder post-stroke recovery but also elevate mortality rates. Despite their profound impact, the precise origins of aberrant amygdala function after a stroke remain elusive. As a target of reduced brain pH in ischemia, acid-sensing ion channels (ASICs) have been implicated in synaptic transmission after ischemia, hinting at their potential role in reshaping neural circuits following a stroke. This study delves into the intriguing relationship between post-stroke alterations and ASICs, specifically focusing on postsynaptic ASIC1a enhancement in the amygdala following prefrontal cortex (PFC) ischemia induced by endothelin-1 (ET-1) injection. Our findings intriguingly illustrate that mPFC ischemia not only accentuates the PFC to the amygdala circuit but also implicates ASIC1a in fostering augmented synaptic plasticity after ischemia. In contrast, the absence of ASIC1a impairs the heightened induction of long-term potentiation (LTP) in the amygdala induced by ischemia. This pivotal research introduces a novel concept with the potential to inaugurate an entirely new avenue of inquiry, thereby significantly enhancing our comprehension of the intricate mechanisms underlying post-stroke neural circuit reconfiguration. Importantly, these revelations hold the promise of paving the way for groundbreaking therapeutic interventions. [ABSTRACT FROM AUTHOR]

Ischemic conditions cause an increase in the sodium concentration of astrocytes, driving the breakdown of ionic homeostasis and exacerbating cellular damage. Astrocytes express high levels of the electrogenic sodium-bicarbonate cotransporter1 (NBCe1), which couples intracellular Na+ homeostasis to regulation of pH and operates close to its reversal potential under physiological conditions. Here, we analyzed its mode of operation during transient energy deprivation via imaging astrocytic pH, Na+, and ATP in organotypic slice cultures of the mouse neocortex, complemented with patch-clamp and ion-selective microelectrode recordings and computational modeling. We found that a 2 min period of metabolic failure resulted in a transient acidosis accompanied by a Na+ increase in astrocytes. Inhibition of NBCe1 increased the acidosis while decreasing the Na+ load. Similar results were obtained when comparing ion changes in wild-type and Nbce1-deficient mice. Mathematical modeling replicated these findings and further predicted that NBCe1 activation contributes to the loss of cellular ATP under ischemic conditions, a result confirmed experimentally using FRET-based imaging of ATP. Altogether, our data demonstrate that transient energy failure stimulates the inward operation of NBCe1 in astrocytes. This causes a significant amelioration of ischemia-induced astrocytic acidification, albeit at the expense of increased Na+ influx and a decline in cellular ATP. [ABSTRACT FROM AUTHOR]

(1) Objective: This study aimed to construct a machine learning model for predicting the prognosis of ischemic stroke patients who underwent thrombolysis, assessed through the modified Rankin Scale (mRS) score 90 days after discharge. (2) Methods: Data were sourced from Qatar's stroke registry covering January 2014 to June 2022. A total of 723 patients with ischemic stroke who had received thrombolysis were included. Clinical variables were examined, encompassing demographics, stroke severity indices, comorbidities, laboratory results, admission vital signs, and hospital-acquired complications. The predictive capabilities of five distinct machine learning models were rigorously evaluated using a comprehensive set of metrics. The SHAP analysis was deployed to uncover the most influential predictors. (3) Results: The Support Vector Machine (SVM) model emerged as the standout performer, achieving an area under the curve (AUC) of 0.72. Key determinants of patient outcomes included stroke severity at admission; admission systolic and diastolic blood pressure; baseline comorbidities, notably hypertension (HTN) and coronary artery disease (CAD); stroke subtype, particularly strokes of undetermined origin (SUO); and hospital-acquired urinary tract infections (UTIs). (4) Conclusions: Machine learning can improve early prognosis prediction in ischemic stroke, especially after thrombolysis. The SVM model is a promising tool for empowering clinicians to create individualized treatment plans. Despite limitations, this study contributes to our knowledge and encourages future research to integrate more comprehensive data. Ultimately, it offers a pathway to improve personalized stroke care and enhance the quality of life for stroke survivors. [ABSTRACT FROM AUTHOR]

The volume of infarcted tissue in patients with ischemic stroke is consistently associated with increased morbidity and mortality. Initial studies of endovascular thrombectomy for large-vessel occlusion excluded patients with established large-core infarcts, even when large volumes of salvageable brain tissue were present, due to the high risk of hemorrhagic transformation and reperfusion injury. However, recent retrospective and prospective studies have shown improved outcomes with endovascular thrombectomy, and several clinical trials were recently published to evaluate the efficacy of endovascular management of patients presenting with large-core infarcts. With or without thrombectomy, patients with large-core infarcts remain at high risk of in-hospital complications such as hemorrhagic transformation, malignant cerebral edema, seizures, and others. Expert neurocritical care management is necessary to optimize blood pressure control, mitigate secondary brain injury, manage cerebral edema and elevated intracranial pressure, and implement various neuroprotective measures. Herein, we present an overview of the current and emerging evidence pertaining to endovascular treatment for large-core infarcts, recent advances in neurocritical care strategies, and their impact on optimizing patient outcomes. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases the risk of systemic bleeding, including intracerebral hemorrhage (ICH). AF-related strokes are associated with greater disability and mortality compared to non-AF strokes. The management of patients with AF-related strokes is challenging, and it involves weighing individual risks and benefits in the acute treatment and preventive strategies of these patients. This review summarizes the current knowledge of the acute management of ischemic and hemorrhagic stroke in patients with AF, and the prognosis and potential implications for management both in the acute and long-term setting. [ABSTRACT FROM AUTHOR]

We investigated prognostic strategies for predicting good outcomes in the early stage of post-cardiac-arrest care using multiple prognostic tests that are available until 24 h after the return of spontaneous circulation (ROSC). A retrospective analysis was conducted on 138 out-of-hospital cardiac-arrest patients who underwent prognostic tests, including the gray–white-matter ratio (GWR-BG), the Glasgow Coma Scale motor (GCS-M) score before sedative administration, and the neuron-specific enolase (NSE) level measured at 24 h after the ROSC. We investigated the prognostic performances of the tests as single predictors and in various combination strategies. Classification and regression-tree analysis were used to provide a reliable model for the risk stratification. Out of all the patients, 55 (44.0%) had good outcomes. The NSE level showed the highest prognostic performance as a single prognostic test and provided improved specificities (>70%) and sensitivities (>98%) when used in combination strategies. Low NSE levels (≤32.1 ng/mL) and high GCS-M (≥4) scores identified good outcomes without misclassification. The overall accuracy for good outcomes was 81.8%. In comatose patients with low NSE levels or high GCS-M scores, the premature withdrawal of life-sustaining therapy should be avoided, thereby complying with the formal prognostication-strategy algorithm after at least 72 h from the ROSC. [ABSTRACT FROM AUTHOR]

S100B is a calcium-binding protein mainly concentrated in astrocytes in the nervous system. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress, and more recently, mounting evidence points to S100B as a Damage-Associated Molecular Pattern molecule, which, at high concentration, triggers tissue reactions to damage. S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease. In addition, in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic and vascular acute neural injury, epilepsy, and inflammatory bowel disease, alteration of S100B levels correlates with the occurrence of clinical and/or toxic parameters. In general, overexpression/administration of S100B worsens the clinical presentation, whereas deletion/inactivation of the protein contributes to the amelioration of the symptoms. Thus, the S100B protein may be proposed as a common pathogenic factor in different disorders, sharing different symptoms and etiologies but appearing to share some common pathogenic processes reasonably attributable to neuroinflammation. [ABSTRACT FROM AUTHOR]

Stroke is an emergency in which delays in treatment can lead to significant loss of neurological function and be fatal. Technologies that increase the speed and accuracy of stroke diagnosis or assist in post-stroke rehabilitation can improve patient outcomes. No resource exists that comprehensively assesses artificial intelligence/machine learning (AI/ML)-enabled technologies indicated for the management of ischemic and hemorrhagic stroke. We queried a United States Food and Drug Administration (FDA) database, along with PubMed and private company websites, to identify the recent literature assessing the clinical performance of FDA-approved AI/ML-enabled technologies. The FDA has approved 22 AI/ML-enabled technologies that triage brain imaging for more immediate diagnosis or promote post-stroke neurological/functional recovery. Technologies that assist with diagnosis predominantly use convolutional neural networks to identify abnormal brain images (e.g., CT perfusion). These technologies perform comparably to neuroradiologists, improve clinical workflows (e.g., time from scan acquisition to reading), and improve patient outcomes (e.g., days spent in the neurological ICU). Two devices are indicated for post-stroke rehabilitation by leveraging neuromodulation techniques. Multiple FDA-approved technologies exist that can help clinicians better diagnose and manage stroke. This review summarizes the most up-to-date literature regarding the functionality, performance, and utility of these technologies so clinicians can make informed decisions when using them in practice. [ABSTRACT FROM AUTHOR]

The KCNA1 gene encodes Kv1.1 voltage-gated potassium channel α subunits, which are crucial for maintaining healthy neuronal firing and preventing hyperexcitability. Mutations in the KCNA1 gene can cause several neurological diseases and symptoms, such as episodic ataxia type 1 (EA1) and epilepsy, which may occur alone or in combination, making it challenging to establish simple genotype–phenotype correlations. Previous analyses of human KCNA1 variants have shown that epilepsy-linked mutations tend to cluster in regions critical for the channel's pore, whereas EA1-associated mutations are evenly distributed across the length of the protein. In this review, we examine 17 recently discovered pathogenic or likely pathogenic KCNA1 variants to gain new insights into the molecular genetic basis of KCNA1 channelopathy. We provide the first systematic breakdown of disease rates for KCNA1 variants in different protein domains, uncovering potential location biases that influence genotype–phenotype correlations. Our examination of the new mutations strengthens the proposed link between the pore region and epilepsy and reveals new connections between epilepsy-related variants, genetic modifiers, and respiratory dysfunction. Additionally, the new variants include the first two gain-of-function mutations ever discovered for KCNA1, the first frameshift mutation, and the first mutations located in the cytoplasmic N-terminal domain, broadening the functional and molecular scope of KCNA1 channelopathy. Moreover, the recently identified variants highlight emerging links between KCNA1 and musculoskeletal abnormalities and nystagmus, conditions not typically associated with KCNA1. These findings improve our understanding of KCNA1 channelopathy and promise to enhance personalized diagnosis and treatment for individuals with KCNA1-linked disorders. [ABSTRACT FROM AUTHOR]

Background: There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery. Objective: This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI. Methods: In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines. Results: The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another. Conclusion: For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered. [ABSTRACT FROM AUTHOR]

Dry electroencephalogram (EEG) systems have a short set-up time and require limited skin preparation. However, they tend to require strong electrode-to-skin contact. In this study, dry EEG electrodes with low contact impedance (<150 kΩ) were fabricated by partially embedding a polyimide flexible printed circuit board (FPCB) in polydimethylsiloxane and then casting them in a sensor mold with six symmetrical legs or bumps. Silver–silver chloride paste was used at the exposed tip of each leg or bump that must touch the skin. The use of an FPCB enabled the fabricated electrodes to maintain steady impedance. Two types of dry electrodes were fabricated: flat-disk electrodes for skin with limited hair and multilegged electrodes for common use and for areas with thick hair. Impedance testing was conducted with and without a custom head cap according to the standard 10–20 electrode arrangement. The experimental results indicated that the fabricated electrodes exhibited impedance values between 65 and 120 kΩ. The brain wave patterns acquired with these electrodes were comparable to those acquired using conventional wet electrodes. The fabricated EEG electrodes passed the primary skin irritation tests based on the ISO 10993-10:2010 protocol and the cytotoxicity tests based on the ISO 10993-5:2009 protocol. [ABSTRACT FROM AUTHOR]

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system. [ABSTRACT FROM AUTHOR]

With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing. [ABSTRACT FROM AUTHOR]

Cerebral ischemia/reperfusion (CI/R) injury causes high disability and mortality. Hydrogen (H2) enhances tolerance to an announced ischemic event; however, the therapeutic targets for the effective treatment of CI/R injury remain uncertain. Long non-coding RNA lincRNA-erythroid prosurvival (EPS) (lincRNA-EPS) regulate various biological processes, but their involvement in the effects of H2 and their associated underlying mechanisms still needs clarification. Herein, we examine the function of the lincRNA-EPS/Sirt1/autophagy pathway in the neuroprotection of H2 against CI/R injury. HT22 cells and an oxygen-glucose deprivation/reoxygenation (OGD/R) model were used to mimic CI/R injury in vitro. H2, 3-MA (an autophagy inhibitor), and RAPA (an autophagy agonist) were then administered, respectively. Autophagy, neuro-proinflammation, and apoptosis were evaluated by Western blot, enzyme-linked immunosorbent assay, immunofluorescence staining, real-time PCR, and flow cytometry. The results demonstrated that H2 attenuated HT22 cell injury, which would be confirmed by the improved cell survival rate and decreased levels of lactate dehydrogenase. Furthermore, H2 remarkably improved cell injury after OGD/R insult via decreasing pro-inflammatory factors, as well as suppressing apoptosis. Intriguingly, the protection of H2 against neuronal OGD/R injury was abolished by rapamycin. Importantly, the ability of H2 to promote lincRNA-EPS and Sirt1 expression and inhibit autophagy were abrogated by the siRNA-lincRNA-EPS. Taken together, the findings proved that neuronal cell injury caused by OGD/R is efficiently prevented by H2 via modulating lincRNA-EPS/Sirt1/autophagy-dependent pathway. It was hinted that lincRNA-EPS might be a potential target for the H2 treatment of CI/R injury. [ABSTRACT FROM AUTHOR]

The complex synaptic connectivity architecture of neuronal networks underlies cognition and brain function. However, studying the spiking activity propagation and processing in heterogeneous networks in vivo poses significant challenges. In this study, we present a novel two-layer PDMS chip that facilitates the culturing and examination of the functional interaction of two interconnected neural networks. We utilized cultures of hippocampal neurons grown in a two-chamber microfluidic chip combined with a microelectrode array. The asymmetric configuration of the microchannels between the chambers ensured the growth of axons predominantly in one direction from the Source chamber to the Target chamber, forming two neuronal networks with unidirectional synaptic connectivity. We showed that the local application of tetrodotoxin (TTX) to the Source network did not alter the spiking rate in the Target network. The results indicate that stable network activity in the Target network was maintained for at least 1–3 h after TTX application, demonstrating the feasibility of local chemical activity modulation and the influence of electrical activity from one network on the other. Additionally, suppression of synaptic activity in the Source network by the application of CPP and CNQX reorganized spatio-temporal characteristics of spontaneous and stimulus-evoked spiking activity in the Target network. The proposed methodology and results provide a more in-depth examination of the network-level functional interaction between neural circuits with heterogeneous synaptic connectivity. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac arrest is a significant cause of premature mortality and severe disability. Despite the death rate steadily decreasing over the previous decade, only 22% of survivors achieve good clinical status and only 25% of patients survive until their discharge from the hospital. The objective of this scoping review was to review relevant AI modalities and the main potential applications of AI in resuscitation. Methods: We conducted the literature search for related studies in PubMed, EMBASE, and Google Scholar. We included peer-reviewed publications and articles in the press, pooling and characterizing the data by their model types, goals, and benefits. Results: After identifying 268 original studies, we chose 59 original studies (reporting 1,817,419 patients) to include in the qualitative synthesis. AI-based methods appear to be superior to traditional methods in achieving high-level performance. Conclusion: AI might be useful in predicting cardiac arrest, heart rhythm disorders, and post-cardiac arrest outcomes, as well as in the delivery of drone-delivered defibrillators and notification of dispatchers. AI-powered technologies could be valuable assistants to continuously track patient conditions. Healthcare professionals should assist in the research and development of AI-powered technologies as well as their implementation into clinical practice. [ABSTRACT FROM AUTHOR]

Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials (RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies. [ABSTRACT FROM AUTHOR]

Neuronal cultures are one of the most important experimental models in modern interdisciplinary neuroscience, allowing to investigate in a control environment the emergence of complex behavior from an ensemble of interconnected neurons. Here, I review the research that we have conducted at the neurophysics laboratory at the University of Barcelona over the last 15 years, describing first the neuronal cultures that we prepare and the associated tools to acquire and analyze data, to next delve into the different research projects in which we actively participated to progress in the understanding of open questions, extend neuroscience research on new paradigms, and advance the treatment of neurological disorders. I finish the review by discussing the drawbacks and limitations of neuronal cultures, particularly in the context of brain-like models and biomedicine. [ABSTRACT FROM AUTHOR]

Introduction: Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization. Methods: Adult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan <24 h post-injury. Neuroworsening was defined as a decline in motor GCS at ED disposition (vs. ED admission). Clinical and CT characteristics, neurosurgical intervention, in-hospital mortality, and 3- and 6-month Glasgow Outcome Scale-Extended (GOS-E) scores were compared by neuroworsening status. Multivariable regressions were performed for neurosurgical intervention and unfavorable outcome (GOS-E ≤ 3). Multivariable odds ratios (mOR) with [95% confidence intervals] were reported. Results: In 481 subjects, 91.1% had ED admission GCS 13–15 and 3.3% had neuroworsening. All neuroworsening subjects were admitted to intensive care unit (vs. non-neuroworsening: 26.2%) and were CT-positive for structural injury (vs. 45.4%). Neuroworsening was associated with subdural (75.0%/22.2%), subarachnoid (81.3%/31.2%), and intraventricular hemorrhage (18.8%/2.2%), contusion (68.8%/20.4%), midline shift (50.0%/2.6%), cisternal compression (56.3%/5.6%), and cerebral edema (68.8%/12.3%; all p < 0.001). Neuroworsening subjects had higher likelihoods of cranial surgery (56.3%/3.5%), intracranial pressure (ICP) monitoring (62.5%/2.6%), in-hospital mortality (37.5%/0.6%), and unfavorable 3- and 6-month outcome (58.3%/4.9%; 53.8%/6.2%; all p < 0.001). On multivariable analysis, neuroworsening predicted surgery (mOR = 4.65 [1.02–21.19]), ICP monitoring (mOR = 15.48 [2.92–81.85], and unfavorable 3- and 6-month outcome (mOR = 5.36 [1.13–25.36]; mOR = 5.68 [1.18–27.35]). Conclusions: Neuroworsening in the ED is an early indicator of TBI severity, and a predictor of neurosurgical intervention and unfavorable outcome. Clinicians must be vigilant in detecting neuroworsening, as affected patients are at increased risk for poor outcomes and may benefit from immediate therapeutic interventions. [ABSTRACT FROM AUTHOR]

Intraoperative adverse events (iAEs) impact the outcomes of surgery, and yet are not routinely collected, graded, and reported. Advancements in artificial intelligence (AI) have the potential to power real-time, automatic detection of these events and disrupt the landscape of surgical safety through the prediction and mitigation of iAEs. We sought to understand the current implementation of AI in this space. A literature review was performed to PRISMA-DTA standards. Included articles were from all surgical specialties and reported the automatic identification of iAEs in real-time. Details on surgical specialty, adverse events, technology used for detecting iAEs, AI algorithm/validation, and reference standards/conventional parameters were extracted. A meta-analysis of algorithms with available data was conducted using a hierarchical summary receiver operating characteristic curve (ROC). The QUADAS-2 tool was used to assess the article risk of bias and clinical applicability. A total of 2982 studies were identified by searching PubMed, Scopus, Web of Science, and IEEE Xplore, with 13 articles included for data extraction. The AI algorithms detected bleeding (n = 7), vessel injury (n = 1), perfusion deficiencies (n = 1), thermal damage (n = 1), and EMG abnormalities (n = 1), among other iAEs. Nine of the thirteen articles described at least one validation method for the detection system; five explained using cross-validation and seven divided the dataset into training and validation cohorts. Meta-analysis showed the algorithms were both sensitive and specific across included iAEs (detection OR 14.74, CI 4.7–46.2). There was heterogeneity in reported outcome statistics and article bias risk. There is a need for standardization of iAE definitions, detection, and reporting to enhance surgical care for all patients. The heterogeneous applications of AI in the literature highlights the pluripotent nature of this technology. Applications of these algorithms across a breadth of urologic procedures should be investigated to assess the generalizability of these data. [ABSTRACT FROM AUTHOR]

The neurovascular unit (NVU) is an anatomical group of cells that establishes the blood–brain barrier (BBB) and coordinates cerebral blood flow in association with neuronal function. In cerebral gray matter, cellular constituents of the NVU include endothelial cells and associated pericytes, astrocytes, neurons, and microglia. Dysfunction of the NVU is a common feature of diseases that affect the CNS, such as ischemic stroke. High-level evaluation of these NVU changes requires the use of imaging modalities that can enable the visualization of various cell types under disease conditions. In this study, we applied our confocal microscopy strategy using commercially available labeling reagents to, for the first time, simultaneously investigate associations between endothelial cells, the vascular basal lamina, pericytes, microglia, astrocytes and/or astrocyte end-feet, and neurites in both healthy and ischemic brain tissue. This allowed us to demonstrate ischemia-induced astrocyte activation, neurite loss, and microglial migration toward blood vessels in a single confocal image. Furthermore, our labeling cocktail enabled a precise quantification of changes in neurites and astrocyte reactivity, thereby showing the relationship between different NVU cellular constituents in healthy and diseased brain tissue. The application of our imaging approach for the simultaneous visualization of multiple NVU cell types provides an enhanced understanding of NVU function and pathology, a state-of-the-art advancement that will facilitate the development of more effective treatment strategies for diseases of the CNS that exhibit neurovascular dysfunction, such as ischemic stroke. [ABSTRACT FROM AUTHOR]