Cover image: The cover image is based on the article Alterations of Metabolome and Lipidome in Patients with In-Stent Restenosis by Ziqi Xu et al., https://doi.org/10.1111/cns.14832.

The cover image is based on the article Exploring Functional and Structural Connectivity Disruptions in Spinocerebellar Ataxia Type 3: Insights from Gradient Analysis by Xingang Wang et al., https://doi.org/10.1111/cns.14842.

In this study, a total of 32,715 patients with acute ischemic stroke undergoing endovascular thrombectomy (EVT) were included. In total, 29,628 patients (90.6%) were not taking a vitamin K antagonist (VKA) prior to stroke, and 3087 patients (9.4%) were taking a VKA. The incidence of symptomatic intracranial hemorrhage (sICH) among the VKA group is 6.8%, which is comparable to those non-VKA users with an incidence of 6.4%. Then, the international normalized ratio (INR) was dichotomized as ≤1.7 and >1.7 to assess the risk of sICH in each subgroup. Among 830 patients taking a VKA with an INR greater than 1.7, the incidence of sICH was 8.3%, which is significantly higher than those not taking a VKA (6.4%). Meanwhile, those with an INR of 1.7 or lower (n = 1585) had no significant difference of the risk of sICH (6.7%).

GSK3 signaling in Alzheimer's disease and targeted therapies.

Wallerian degeneration (WD) of bilateral middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary neurodegenerative disorder. WD of bilateral (MCPs) does not seem to be a marker for a bad outcome in general. The radiological features in MRI included hyperintense T2WI signals, hyperintense FLAIR signals, high DWI signal intensity, and low ADC signal intensity.

Perioperative stroke (PIS) exacerbates post-stroke demyelination and worsens neurological functions by promoting infiltration of CD8⁺ T cells and microglia necroptosis in experimental animal models. Pharmacological blockage or genetic deletion of receptor-interacting protein kinase 1 activity could partly reverse demyelination injury, suggesting a novel therapeutic target for the PIS treatment.

Changes of in the visual cortex were observed before the progression to dysthyroid optic neuropathy (DON). With the onset of DON, significant intraorbital optic nerve compression was noted, accompanied by further alterations in the visual cortex and other brain regions. This provides novel explanations of visual pathway alterations in DON.

The present study investigates diagnostic and predictive role of ¹⁸F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. Our findings suggest that ¹⁸F-FDG PET/CT is more sensitive than MRI in the early diagnosis of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism is a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

To identify novel TRP channel gene clusters and describe their characteristics, we conducted an unsupervised clustering algorithm. Based on eight independent glioma cohorts and ten machine learning algorithms, a TRP-related signature was constructed named MLTS. It provides a well-developed and robust model to predict prognosis and immunotherapy response in gliomas.

Recombinant human tissue plasminogen activator (rtPA) activates neutrophils, enhancing their migration and adhesion, which participate in the side effect of rtPA.

Metabolomic and lipidomic analysis showed that patients who developed in-stent restenosis (ISR) had significantly increased expression of L-methionine and N-formyl-l-methionine, and significantly decreased expression of triacylglycerol in their serum. Phenol sulfate and PS(38:4) may be potential biomarkers for the diagnosis of ISR.

The sex-dependent treatment effect of PD-L1 in PIPN mice was related to the difference in the expression of TRPV1 and CGRP in the spinal cords of PIPN mice of both sexes.

Increased LHb neuronal excitability, which potentially resulted from enhanced function of HCN channels and increased expression of HCN2 isoforms, is crucial for the development of CADS in chronic pain. Either bilateral microinjection of ZD7288 into the LHb to inhibit HCN channels or the specific knockdown of HCN2 channels could obviously decrease the LHb neuronal excitability and produce significant analgesic and antidepressant effects.

CD300LF⁺ microglia inhibit neuroinflammation after TBI and promote neurological recovery in TBI patients by inhibiting the cGAS-STING pathway while promoting JAK2-STAT6 signaling pathway activity.

Causality between PM2.5 and amyotrophic lateral sclerosis has been identified via two-sample Mendelian randomization for the first time, with single nucleotide polymorphisms from genome-wide association study serving as instrumental variables. C9orf72 turned out to be the top gene in the transcriptome-wide association analysis. The figure was created by Biorender.com.

A novel functional metabolomics strategy was developed to establish relationships between changes in gene expression and metabolic phenotypes, which identified nicotinamide as a potential functional metabolite that suppressed fibrotic scar formation by suppressing the TGFβ/SMADs pathway in mice after SCI.

The NMOSD model demonstrated substantial neuroinflammation and neural injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that exacerbates disease pathogenesis. Notably, GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders.

A novel method predicts outcomes in traumatic brain injury (TBI) patients using electronic health record (EHR) data and physiological time-series (PTS) signals. Interpretable machine learning techniques identify effective models and offer clinical insights.

Heat stress affects the gut microbiota (TM7, Lactobacillus spp., Ruminococcus spp., and [Prevotella] spp.), which in turn acts on the PERK/eIF2α/ATF4/CHOP, TLR4/NF-κB, and TLR4/p38MAPK signaling pathways to induce endoplasmic reticulum stress (ERS) and ERS-dependent neuroinflammation, whereas β-Hydroxybutyric acid exerts a potential therapeutic role in HS-induced neuroinflammation in mice via the gut–brain axis.

The olfactory performance of ALS patients is correlated with cognitive impairment, particularly frontotemporal dysfunction.

BMI >22.64 kg/m² emerges as a substantial and independent risk factor for perioperative ischemic stroke. A more stringent perioperative weight management approach is recommended, particularly for specific subgroups such as female patients, those with coronary heart disease and peripheral vascular disease, and individuals scheduled for neurosurgery.

In the experimental model of Alzheimer's disease, caloric restriction attenuated severity of the disease, improved ability of learning and spatial memory, and decreased Aβ expression. The caloric restriction resulted in significant alteration of composition and abundance of gut flora.

Salivary and plasma levetiracetam concentrations had a linear relationship and similar changes during pregnancy, which supported the effective use of saliva in levetiracetam therapeutic drug monitoring during pregnancy.

G1 improved PTSD-like behaviors in SPS mice, possibly by increasing hippocampal GPER1 expression and promoting BDNF/TrkB signaling to repair synaptic and mitochondrial functional impairments.

This study employs single-cell transcriptomic analysis to identify subgroups of glioblastoma-associated macrophages. Spatial transcriptomic analysis reveals the spatial distribution of macrophages within glioblastoma tissue. In vitro experiments demonstrate that inhibition of MS4A4A reduces the immunosuppressive function of M2-type macrophages. In vivo experiments confirm that inhibition of MS4A4A enhances the response of glioblastoma to PD-1 immunotherapy. This study provides new theoretical bases and molecular therapeutic targets for the diagnosis and treatment of glioblastoma.

Recent advancements in artificial intelligence, particularly deep learning, have revolutionized the detection and evaluation of cerebral small vessel disease (CSVD) through magnetic resonance imaging (MRI). This study demonstrates how deep learning can extract high-dimensional imaging features, improving the quantitative assessment of CSVD, and leading to earlier diagnosis and better patient outcomes.

The WMH volume, primary-to-transmodal gradient, and cognition were interrelated. The detrimental effect of the frontal/occipital WMH on executive function was mediated by the decreased differentiation of the connectivity pattern between the primary and transmodal areas.

This is a pharmacovigilance study to comprehensively assess the correlation between cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) and psychiatric adverse events (PAEs). Our study identified 17 categories of PAEs highly associated with CDK4/6i through disproportionality analysis, and revealed differences in the profiles of PAEs among three CDK4/6i.

This study showed that the expression of necroptosis-related proteins increased after spinal cord injury (SCI). Exendin-4 (EX-4) played a therapeutic role via promoting the recovery of lysosome function and autophagy flux and accelerating the degradation of necroptosis-related proteins by inhibiting the phosphorylation level of mTOR in neurons. This finding may provide a new therapeutic target in clinical treatment after SCI.

After stroke, hypoxia causes a series of pathological events, including energy deficiency, mitochondrial dysfunction, oxidative stress, neuroinflammation, and excitoxicity. NBO treatment rescues this pathological process and has a neuroprotective effect.

Exploring baseline brain functional network differences and identifying indicators for effectively distinguishing progressive subjective cognitive decline (P-SCD) and stable subjective cognitive decline (S-SCD).

The Unfolded protein response is suggested as a therapeutic target for glioblastoma. The unfolded protein response is activated in response to endoplasmic reticulum stress in glioblastoma cells. Its three arms IRE1, PERK, and ATF6 activate their downstream pathways furthering tumor cell survival, proliferation and the development of chemoresistance. Furthermore, targeting the UPR arms induces apoptosis in glioblastomacells. Adapted from "UPR signaling (ATF6, PERK, IRE1)", by BioRender.com(2024). Retrieved from https://app.biorender.com/biorender-templates.

A post hoc analysis of ARAMIS trial demonstrated that among patients with minor nondisabling acute ischemic stroke, dual antiplatelet was better than alteplase with respect to preventing early neurological deterioration within 24 h when baseline systolic blood pressure ≥140 mmHg.

Aβ-PET and CSF p-tau181 were related to cognitive decline across the AD clinical spectrum, both as potential predictors for dementia progression. Aβ-PET (A + T− subjects) was an independent reliable predictor of longitudinal cognitive decline rather than tau pathology (A − T+ subjects), indicating tau accumulation was not closely correlated with future cognitive impairment without being driven by Aβ deposition. Stronger predictive value of Aβ pathology (A+ alone) than tau accumulation (T+ alone) for longitudinal cognitive decline in APOE ε4 carriers.

The current study demonstrated for the first time that: (1) Indicators based on the ATN framework using CSF biomarkers had better diagnostic and prognostic power for RPDs, especially for autoantibodies-negative AE subjects. (2) Indicators based on the ATN framework using serum biomarkers still showed diagnostic value, which provides efficient clinical information for early recognition of treatment-responsive causes of RPDs.

We found that the disruption of functional connectivity between subcortical and cortical regions by general anesthesia is a shared functional mechanism of various anesthetics. Moreover, the increased network and functional properties of higher-order and unimodal cortical regions imply that the information flow required for consciousness is impaired within and between cortical and subcortical regions.

The experiment adhered to rigorous scientific methodologies and protocols, conducting the operational process with utmost attention to detail. FCG Values: functional connectivity gradient values; FC Values: functional connectivity values; FA Values: fractional anisotropy values; FC: functional connectivity; SC: structural connectivity. Four distinct gradient construction patterns and their corresponding inter-group differential brain region were identified (A.B.C.D).

Inflammatory pain in childhood leads to social preference disorders, while BWT in childhood leads to social novelty disorders in adult mice. Inflammatory pain and BWT in childhood caused an increase in the number of PV and SST neurons, respectively, in adult mice ACC. Inhibiting PV neurons in ACC improved social preference disorders in adult mice that experienced inflammatory pain during childhood. Inhibiting SST neurons in ACC improved social novelty disorders in adult mice that experienced BWT in childhood. PV and SST neurons of the ACC may play a critical role in regulating social disorders induced by sensory abnormalities in childhood.

Blood–brain barrier disruption and immune system infiltration after intracerebral hemorrhage.

In summary, this study has revealed the role of NDC80/HEC1 in the process of glioma development and in the tumor microenvironment of glioma. The immunosuppressive property and role of HEC1 make it attractive to be used as novel prognostic biomarkers or effective therapeutic targets. Immunofluorescence of glioma tissue microarrays showed positive correlation of HEC1 expression with the malignancy degrees of glioma and a lower probability of patients with high HEC1 expression. In particular, HEC1 promotes development of glioma through the regulation of cell proliferation, cell cycle, DNA repair, and TME formation, possibly through transcriptional activation of E2F8. Moreover, tumor cells exhibiting HEC1 expression could shape the TME by interacting with macrophage and cancer-associated fibroblasts. Coculture confirmed that glioma cells devied-HEC1 promote macrophage migration and transform into M2. Our results provide further insight into the application of HEC1 in glioma (by Figdraw).

This study provides further evidence supporting safety of anti-seizure medications reduction or withdrawal during ketogenic diet therapy in both adult and children patients with drug-resistant epilepsy. Additionally, it highlights that early anti-seizure medication reduction does not impact long-term outcomes of ketogenic diet therapy.

The long-term efficacy of VNS was assessed among 65 pediatric patients. Presurgical EEG analysis shows that VNS responders exhibit higher nodal efficiency in parietal-occipital EEG α activity and lower entropy in central-frontal EEG θ activity. The SVM model with clinical and EEG features for VNS efficacy shows high accuracy.

Acute sleep deprivation leads to cognitive deficits and disturbances in sleep structure, which are associated with microglia activation. Propofol works by inhibiting microglia, promoting the conversion of M1 to M2, reducing neuroinflammation, improving sleep quality, and reversing the cognitive deficits caused by sleep deprivation.

The main hallmarks of AD are leading to neuron loss and neuron degeneration in AD.

Compared to HCs and NA-PD patients, A-PD patients exhibited significantly reduced GMV in the fusiform gyrus and right inferior temporal gyrus. Our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.

Our study aimed to identify a predictive model for anhedonia symptoms using connectome-based predictive modeling (CPM) in major depressive disorder (MDD). The abnormal functional connectivity patterns between the default mode network and the limbic network in the predictive networks serve as potential neurobiological markers to distinguish between melancholic and non-melancholic MDD. These findings revealed distinct neural substrates for anhedonia symptoms in melancholic and non-melancholic MDD.

Ferroptosis plays a pivotal role in the pathogenesis of cerebral infarction, where the delicate balance between pro- and anti-ferroptotic factors critically influences the outcomes of an ischemic stroke. Our review aims to comprehensively elucidate the underlying mechanisms of ferroptosis and explore therapeutic strategies targeting ferroptosis in ischemic stroke.

Knockdown of the lncRNA H19 significantly promotes recovery from traumatic brain injury (TBI) in mice, as evidenced by reduced neuroinflammation, attenuated tissue damage including gray and white matter, and improved neurological function. This neuroprotective effect was significantly mediated by activation of the Nrf2/HO-1 signaling pathway, revealing a potential target for therapeutic strategies for TBI.

Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP.

METTL14-mediated upregulation of HOTAIR has a potency to repress the expression of PP1α and facilitate the recruitment of LSD1, thus catalyzing H3K4me1 demethylation and promoting oxycodone addiction.

Mutations and expression changes of adenylyl cyclase 2 (Adcy2), a CNS-enriched enzyme that converts ATP to cAMP, are associated with several neurodegenerative and psychiatric disorders.

We found the shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease. We found association between plasma proteins corresponding to the shared genes and COVID-19 outcomes using high-throughput plasma proteomic profiling.

When astrocytes are exposed to neurotoxins (MPTP or rotenone), they undergo senescence and release excessive SASP factors such as IL-6, IL-1β, CXCL10, and MMP9. These SASP factors can harm nearby dopaminergic neurons. However, with the P7C3 treatment, senescent astrocytes could promote NRF2 nuclear translocation, leading to an increase in SIRT3 expression. This, in turn, further promotes mitophagy and inhibits mitoROS production, ultimately protecting dopaminergic neurons from damage.

This graphical abstract depicts evolving brain functional asymmetry in early-stage Parkinson's disease (ePD). Comparing ePD mild and moderate groups with controls reveals increasing asymmetry akin to Lewy body spread from lower to higher brain regions. This insight offers a novel perspective on PD neuropathology and a potential progression biomarker.

Melatonin is a hormone produced in the pineal gland, for adjusting the circadian rhythm of a vertebrate, particularly a mammal. In this study, it may ameliorate SCOP-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the key target of melatonin in the treatment of dementia.

The expression of p75^NTR and the interaction of p75^NTR-VHL were decreased in the ipsilateral VPN after dMCAO, which in turn, increased the VHL-HIF-1α interaction, promoted the degradation of HIF-1α via ubiquitin proteasome pathway, downregulated the expression of VEGF and inhibited angiogenesis, ultimately leading to secondary thalamic damage. Instead, neuronal-targeted p75^NTR overexpression enhanced the interaction of p75^NTR-VHL and upregulated the expression of HIF-1α and VEGF in the ipsilateral VPN through inhibiting HIF-1α ubiquitination degradation mediated by VHL, which facilitates angiogenesis and increases CBF, consequently alleviating secondary thalamic damage after dMCAO.

Insulin improves LPS-induced cognitive impairment and alleviates LPS induced ferroptosis by promoting pentose phosphate pathway of glucose metabolism.

This study shows that compared with treatment with melatonin, coenzyme Q10, or lecithin alone, combined treatment results in more significant effects in reducing oxidative stress and tau protein phosphorylation, and alleviating oxidative stress-mediated impairments in learning and memory.

By employing the advanced CyTOF technique, we conducted an in-depth analysis to uncover the protective mechanisms of AGNHW. Leveraging the precision of CyTOF, our study provides a comprehensive understanding of AGNHW's therapeutic potential in ischemic stroke. It emphasizes its dual action, affecting both the cerebral and systemic aspects, and its nuanced modulation of cellular and molecular dynamics.

Content of the study. First, functional near-infrared spectroscopy and transcranial magnetic stimulation assessments were conducted, followed by feature extraction. Subsequently, independent t-tests and chi-squared tests were applied to reduce the feature dimensionality, and machine learning models were developed with the retained features. Finally, the performance of the models was evaluated by the area under the receiver operating characteristic curve and accuracy. Bayesian models effectively distinguished subgroups and identified the premotor cortex–primary motor cortex connection as highly contributory.