The cover image is based on the Commentary Non-scheduled short acting opioid to taper off opioids? by Renyu Liu et al., https://doi.org/10.1111/cns.14705.

The reads obtained from 10× genomic platform of traumatic epilepsy and hereditary epilepsy were 39.56 M and 30.08 M. The Q30 of RNA reads over 91.6%. After filtering, 7479 traumatic epilepsy and 9357 hereditary epilepsy cells were left for further study. Over 96.4% of the reads are mapped to GRCh38/GRCm38. The cells were differentially distributed in two groups, with higher oligodendrocytes (6522 vs. 2532) and astrocytes (133 vs. 52), lower microglia (2242 vs. 3811) and neurons (3 vs. 203) were observed in hereditary epilepsy than traumatic epilepsy. The DEGs in four cell clusters were identified, with 25 in oligodendrocytes (13 upregulated and 12 downregulated), 87 in microglia (42 upregulated and 45 downregulated), 222 in astrocytes (115 upregulated and 107 downregulated), and 393 in neurons (305 upregulated and 88 downregulated). MTND1P23 (downregulated), XIST (downregulated), and RPS4Y1 (upregulated) were commonly expressed in four cell clusters. The DEGs in microglia and astrocytes were enriched in IL-17 signaling pathway. Our study explored the cell grouping between traumatic and hereditary epilepsy, and the transcriptome in different cells for the first time. Inflammatory and immune functions might be the main approaches in traumatic temporal lobe epilepsy of neurons.

Painful diabetic neuropathy in the dorsal root ganglion (DRG) induces mitochondrial impairment and sirtuin 3 deficiency, leading to inhibited mitophagy through the FoxO3a-PINK1-Parkin pathway, exacerbating allodynia.

Stigmasterol reduces the cascade reaction of Schwann cells and macrophages by regulating the IL34/CSF1R axis, and reduces the peripheral sensitization caused by neuroinflammation in the dorsal root ganglia (DRG), thereby alleviating neuropathic pain.

The potential of phosphorylated α-Syn (p-syn) as a biomarker for multiple system atrophy diagnosis and monitoring, is defined by the abnormal p-syn accumulation in the brain and peripheral tissues.

AZD1390 suppressed NF-κB signaling pathway through restricting ubiquitylation and sumoylation of NEMO, which alleviated ischemic brain injury in experimental stroke and attenuated the activation of microglia and neuroinflammation.

Spontaneous brain activity (fractional amplitude of low-frequency fluctuation − fALFF) in the hippocampal regions could reveal cognitive levels in patients with Parkinson's disease to differentiate normal cognition, mild cognitive impairment, and severe cognitive impairment.

The downregulation of VAPB-PTPIP51 expression after ischemic stroke mediates structural damage to mitochondria-associated endoplasmic reticulum membranes, which may exacerbate CIRI by regulating the PI3K pathway and activating autophagy.

This review delves into the intricate relationship between the gut microbiota and Alzheimer's disease (AD), unraveling the close association between microbial changes and disease mechanisms. By elucidating relevant pathways, we present promising therapeutic strategies involving the modulation of the gut microbiota, opening new avenues for innovative treatments in AD. Graphical Abstract created By Figdraw.

In this perspective, we are proposing to introduce a non-scheduled short-acting opioid into clinical practice given the significant need to find alternatives to taper off opioids and bridge buprenorphine and methadone therapies for opioid use disorders. Dezocine, a previously FDA approved non-scheduled opioid for pain management, is a potential candidate to explore. Dr. Renyu Liu obtained the images presented in this graphic abstract from Adobe Stock with standard licenses.

Upon ICH, the brain's DMT1 increased but decreased with Lentivirus-induced Nedd4 overexpression, implying a negative correlation. Nedd4 interacted with DMT1 at lysine residues 6, 69, and 277, resulting in ubiquitination and degradation of DMT1. Nedd4 overexpression relieved ferroptosis and aided ICH recovery, as indicated by functional analysis.

mTOR signaling and Alzheimer's disease (AD). Upregulation of mTOR activity appears to be involved in the main pathological cascade of AD, and mTOR inhibition or targeting its downstream substrates could supply attractive avenues for AD treatment.

The NMDAR inhibition is the primary presumptive molecular mechanism underlying the anesthetic and antidepressant effects of ketamine.

The potential synergistically ncRNA-based apoptosis regulatory mechanism exists in AD.

Understanding the role of inflammation in diabetic peripheral neuropathy's progression.

The pathophysiology and treatment in the comorbidity of diabetes mellitus and depression. GM, Gastrointestinal Microbiome; HPA, Hypothalamic–Pituitary–Adrenal. By Figdraw.

CircRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases.

The precise risk factors and molecular mechanisms underlying CNS tumors remain unverified. Growing evidence suggests that Circular RNAs (circRNAs) have numerous significant biological functions in disease progression. In this review, we provide an overview of the relationship between circRNAs and CNS tumors and discuss the diagnostic and therapeutic potential of circRNAs in CNS tumors.

Flow diagram for literature search and screening process.

Brain renin-angiotensin system (RAS).

We performed a cross-sectional study on the cognitive function of the Han elderly population in southern China and the target population coverage rate was high, reaching 73%. A representative prevalence rate of cognitive impairment was obtained, and the relevant risk factors were comprehensively analyzed.

By analyzing DNA methylation microarray data and clinical information of glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT), a panel of 64 CpGs and a 10-CpG risk score signature were discovered and validated with specific linkage to temozolomide (TMZ) efficacy. Experimental data provided biological clues behind the risk signature. The 64 CpGs and in particular the 10-CpG signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in GBMs with G-CIMP- and unMGMT.

The Nestin-Pax2 mice showed increased RRBs at both lower-order and higher-order. Furthermore, alterations in the mPFC→CA1/BLA neural circuitry and a reduction in IGFBP2 can be found in the hippocampus.

Transcriptomic analysis of human cerebral microvascular endothelial cell (HCMEC)/D3 cells subjected to OGD/R showed that the top significantly changed signaling pathways were mostly associated with inflammatory responses, especially the TNF signaling pathway. Reperfusion-induced differentially expressed proteins were primarily involved in extracellular matrix destruction and remodeling, impairment of endothelial transport function, and inflammatory responses.

A TGF-β signaling-related lncRNA signature has been established in glioma, which can be used for prognostic judgment, immune infiltration status speculation, and immunotherapy response prediction. Furthermore, in vitro experiments confirmed that silencing of TGF-β signaling-related lncRNA could inhibit the proliferation of glioma cells. This study provides candidate biomarkers with clinical application value for glioma.

Patients with late-life depression (LLD) exhibited decreased static FC between the right habenula and bilateral IFG compared with healthy controls, and this decreased FC was involved in the underlying pathway connecting psychomotor retardation and deficit of verbal fluency and working memory. The present results provide a more in-depth understanding of their pathological mechanism, and could inform the development of more targeted and effective therapeutic interventions, improving the management and treatment outcomes for LLD.

The quantitative visual score medial temporal lobe atrophy index (QMTA) can be utilized as a clinical diagnostic tool for Alzheimer's disease. When the QMTA value is 0.635 or higher, it may indicate probable Alzheimer's disease.

The full length Dyrk1A phosphorylated ASF and inhibited ASF-mediated Bcl-xL exon 2b inclusion leading to cell apoptosis. Moreover, the truncated Dyrk1A deleting the C-terminus exhibited equidistribution in the nucleoplasm and stronger interaction with ASF, leading to decreased ratio of Bcl-xL/Bcl-xS and neuronal apoptosis in AD.

Adult rats were subjected to CVT and MCAO models. Multi-omics (RNA-seq and untargeted metabolomics) analysis were performed to construct the transcriptome and metabolism profiles of rat brains after CVT and also MCAO. The differential gene analysis, functional annotation, and enrichment analysis were also performed.

Model for integrin α3 involvement in the rTMS-modulated glutamatergic synaptic transmission after PT stroke.

Gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming after DBS in PD patients.

Alzheimer's disease (AD) patients in the dementia stage had worse nutritional status and gait performance than those in the MCI stage. Poorer nutritional status was associated with poorer gait performance in AD patients.

Eomesodermin was highly expressed in the peripheral CD4⁺T-cells derived from ALS patients. Elevated CXCR3 expression in CD4⁺EOMES⁺ T-cells differentiates ALS from HCs. EOMES⁺ subsets were correlated with serum NFL levels. ALS patients with higher EOMES expression were associated with higher progression rates and worse prognosis.

The blockade of PD-1 alleviates neuronal overexcitation by reinstating sodium channel inactivation, indicating anti-PD-1 treatment as a novel therapeutic strategy for epilepsy.

Our findings demonstrate a significant correlation between preoperative high HGB concentrations and the occurrence of DVT following aSAH. This highlights the potential of HGB as an early indicator for identifying patients at high risk of developing DVT.

Pattern diagram illustrating the alleviation of depression induced by crystalline silica through nicotine intervention. Upon exposure to CS, the blood–brain barrier (BBB) in the hippocampus undergoes damage, leading to activation of astrocytes and microglia. The activated astrocytes facilitate the secretion of Lcn2 via the NF-κB pathway, ultimately resulting in neuronal death. However, nicotine mitigates the activation of astrocytes and microglia while safeguarding neurons against cell death.

Survivin is able to regulate neurogenesis in vitro and in vivo model. Our results demonstrate that therapeutic effects of survivin which improves cognitive function by enhancing neurogenesis in 5XFAD mouse. Survivin seems to be a good candidate for therapeutics to restore cognitive function in hippocampus of AD.

sEH inhibition reduced pro-inflammatory processes in vitro and in vivo models, being the eIF2α/CHOP, an undescribed implicated neuroprotective pathway improving cognition and AD hallmarks in 5XFAD mice model by favoring synaptic plasticity, modulating ISR, and apoptosis.

After cerebral ischemia, circPTP4A2 levels increased in peri-infarct cortex and the elevation of circPTP4A2 was mainly located in microglia. Upregulated circPTP4A2 directly binds to STAT3 and promoted STAT3 phosphorylation activation. The phosphorylated STAT3 dimer then enters the nucleus to modulate stroke-induced microglial polarization, which promotes neuroinflammation by driving M1 microglial polarization.

In patients with acute basilar artery occlusion with asymmetric deep cerebral venous filling, the risk of postoperative malignant cerebellar edema and adverse outcome at 90-day follow-up is significantly increased even after complete recanalization.

This study conducted a comprehensive bibliometric and visual analysis of itch research. 2314 papers closely related to itch research published between 2002 and 2021 were retrieved from the SCI-E of Web of Science Core Collection database. Full records and cited references were extracted from relevant publications. Then the data were imported into the Online Analysis Platform of Biobliometry, VOSviewer, CiteSpace software, and Bibliometrix to systematically evaluate publication trends in itch research and predict future research directions.

Carpesii fructus extract (CFE) attenuates H₂O₂- or 6-OHDA-induced toxicity and reduce α-synuclein to inhibit ROS production and restore MMP in PC-12 cells and Caenorhabditis elegans, resulting in the improvement of dopaminergic neurons and motor ability in PD. These effects are involved the regulation of MAPK signaling pathway.

As quantified by multiple scale entropy (MSE), tremor complexity may be a promising marker to capture the pathophysiology underlying the development of Parkinsonian tremor (PT), and help characterize the effects of medication on the complex regulation of PT.

Overall, findings indicate the generation of therapeutic benefits through the simultaneous intravenous and intranasal administration of secretome derived from preconditioned human mesenchymal stem cells, which helps mitigate morphine-induced withdrawal syndrome in two relevant animal models of morphine dependence. These effects were associated with a reduction of morphine-induced neuroinflammation in the hippocampus and nucleus accumbens.

The role of peripheral immune cells in stroke recovery remains unclear. Gu et al. report a phagocytic subset of macrophages and a macrophage-like subset of T cells enhancing brain repair, while natural killer cells decrease cytotoxicity and neutrophils keep cell recruitment. These identified immune components may provide potential therapeutic targets.

ZZCD exerts pleiotropic antidepressant effects by regulating HPA axis and gut microbiota, participating in the process of neuroactive ligand/receptor interaction, regulating the secretion of prolactin and estrogen, and interfering with MAPK and TNF signaling pathways to reduce inflammation levels.

Chronic inflammatory pain induces anxiety-like behaviors, and electroacupuncture ameliorates negative emotions by intervening rACC^CaMKII-DRN^5-HT neural circuit but not the rACC^CaMKII-DRN^GABA circuit.

This pharmacovigilance study is based on real-world data from the FAERS database. Total AEs between the third quarter of 2015 and the first quarter of 2023 were obtained from FAERS. Psychiatric AEs were identified using disproportionality analysis and clinical prioritization of signals using a rating scale, followed by univariate logistic regression to explore factors influencing psychiatric AEs.

This study aims to explore the regional activity within the prefrontal-limbic circuit among drug-naive individuals diagnosed with GAD and panic disorder (PD) and to analyze changes following treatment. To our knowledge, this study is the first to explore the regional activity within the prefrontal-limbic system circuitry using a finely tuned Brainnetome atlas. A major strength of this study is that the abnormal regional activity in the right cHipp subregion of the hippocampus, left A23d and bilateral A32sg subregions of the cingulate, as well as the left A14m and bilateral A12/47L subregions of the orbitofrontal lobe, may be related to anxiety-induced state changes. In addition, high fALFF levels in the right A13 and right A24cd subregions could serve as predictors for individual responses to antipsychotic therapy.

Cauda equina injury (CEI) leads to ferroptosis in mice by raising the expression level of HDAC2, resulting in an increase in MDA and ROS. Ferroptosis in CEI is ameliorated by VPA treatment via suppressing HDAC2.

The radiographic features, including tumor size, fundal fluid cap (FFC) and cerebrospinal fluid cleft (CSFC) sign, and the expansion of the IAC, may serve as good predictors of postoperative facial nerve (FN) outcomes after vestibular schwannoma resection.

Icaritin greatly rescues the phenotypes of the Aβ-induced Drosophila AD model, and its possible mechanism is almost completely restoring the mitochondria damaged by the toxicity of Aβ.

Enhancing the anti-tumor effect of PTX in GBM through self-assembled nanoparticles of natural bioactive molecules with anti P-gp activity, leading to improved water-solubility, BBB permeability, and chemosensitivity of PTX.

Five COQ4 variants were identified in three Chinese HSP pedigrees. Functional studies revealed reduced CoQ10 level and fragmented mitochondria in patient's fibroblast.

Dual-tDCS combined with sensorimotor training can improve upper limb sensory and motor dysfunction, enhance ADL, alleviate depression and anxiety, and enhance the functional connectivity of sensorimotor functional brain cortex for subacute stroke patients.

With a lack of comprehensive comparisons among anti-Parkinson drugs (APDs), this multi-center retrospective study systematically compared the effectiveness, safety, and costs of different APDs. Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk in headache/dizziness, gastrointestinal, and neuropsychiatric symptoms.

Subjects with Parkinson's disease (PD) or PDs exhibit higher mitophagy-associated protein (MAP) levels compared to the CN group, but the differences in values between PD and PDs did not reach significance. The AUCs of PINK1, PGAM5, and Parkin were ranked as the top three MAP candidates in diagnosis accuracy for PD from CN. Higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-syn (+) subjects are higher than in A-syn (−) subjects.

Microsurgery (MS) only and microsurgery with preoperative embolization (E + MS) could significantly prevent the hemorrhagic risk but caused more neurofunctional deficit than conservative management (CM).

A direct PVT-IC glutamate neural circuit playing a critical role in visceral hypersensitivity in a mouse model of IBS. This work will strengthen fundamental research on the involvement of central nervous system in visceral hyperalgesia and provide potential therapeutic targets toward effective treatment.

Here, we found that vof16-miR185-5p-GAP43 network is closely related to SCT self-repair, and simultaneously enhances motor and sensory function after SCT. Knocking out vof16 or GAP43 could inhibit the self-repair of spinal cord and neurite growth, while miR-185-5p knockout promoted the axonal growth after SCT. Furthermore, miR-185-5p can competitively bind the same regulatory region of vof16 and GAP43. Our study provides a novel regulatory network that functions via a miRNA competitive mechanism mediated by vof16 in SCT self-repair and axonal growth.

The proposed pathway by which IRE1α regulates the oxidative stress response via miR-25-3p/Nox4 after ICH. ① ICH induces ER stress and activates the phosphokinase activity of IRE1α. ② Self-phosphorylated IRE1ɑ increases the expression of miR-25-3p. ③ The complementary combination of miR-25-3p with Nox4 mRNA inhibits the translation of Nox4 mRNA and subsequently downregulated expression of Nox4, which leads to ROS production decrease, especially H₂O₂.

This study aimed to investigate multiparametric imaging of the hippocampal radiomics for early diagnosis of AD using simultaneous PET/MRI. Our findings demonstrated that multi-dimensional imaging of the hippocampal radiomics benefits the identification of early AD (aMCI especially) and may provide a potential biomarker for clinical applications in AD.

Significant cortical atrophy was primarily observed in the prefrontal cortex in DRT-treated patients, including bilateral superior frontal cortex (SFC) and left rostral anterior cingulate cortex (rACC). the left SFC volume was negatively correlated with levodopa equivalency dose (LED), as well as the left rACC volume and medication duration.

We explored the cross-sectional and longitudinal retinal structural thicknesses in SSI patients based on their location. We showed at the baseline that thalamic infarction patients had thinner RNFL and GCIPL thicknesses compared with extra-thalamic stroke patients. Longitudinal analysis showed the thinning rate in GCIPL of the thalamic infarction group was significantly higher than that in the extra-thalamic infarction group.

The global efficiency and nodal efficiency were significantly lower in mild cognitive impairment with SSD (MCID), and the accuracy of the support vector machine model was 0.83 for distinguishing MCID from MCIND. MCID is correlated to the greatest disrupted topological organization, which may serve as biomarkers of different MCI subgroups.

This study utilized electrocorticographic (ECoG) power, electromyogram (EMG) amplitude, and corticomuscular coherence (CMC) values to construct sleep–wake scoring and Parkinson's disease (PD) prediction models based on the support vector machine (SVM) algorithm. The models enable precise classification and identification of sleep–wake states and exhibit robust performance across different rats.

Nuclear autoantigenic sperm protein (NASP) plays a crucial role in glioblastoma progression and radioresistance, promotes DNA repair, and activates the STAT3 signaling pathway through ANXA2. The NASP/ANXA2/STAT3 axis is a potential therapeutic target for improving the prognosis of patients with GBM.

Deep sequencing targeting DNA damage repair pathways identifies ARID1A as a prognostic biomarker for gliomas and its mutation alters SWI/SNF stability increasing the malignant phenotype of GBM and mediating chemoresistance.

Framework of identifying the multi-omics molecular biomarkers in brain tumor-related epilepsy (BTRE), including Genomics, Transcriptomics, Epigenomics, Proteomics, and Metabolomics, to facilitate the early diagnosis, etiological factors analysis, and personalized treatment of BTRE.

Quercetin exerts antidepressant neuromodulation by inhibiting α2δ-1, interfering with the interaction between α2δ-1 and NMDAR, and reducing the expression of NMDAR.

Astragaloside IV and Ligustrazine, the main ingredients of medicinal and food homologous plants Astragali Radix and Chuanxiong Rhizoma could ameliorate abnormal mitochondrial dynamics via the Drp1 SUMO/deSUMOylation following cerebral ischemia–reperfusion injury both in vivo and in vitro.

The targeted stimulation of the hyperdirect pathway (M1-STN connectivity) with ccPAS enhanced the functional connectivity between the M1 and STN and subsequently enhanced the balance performance, highlighting the capability and efficacy of ccPAS in regulating brain connectivity associated with functional impairments.

Patients with α-synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model.

The challenge of improving cognitive impairment associated with schizophrenia (CIAS) persists due to the limited availability of novel treatment options and drugs. Our study introduces a novel AMPAR potentiator, LT-102, which could be a potential therapeutic candidate for CIAS by modifying synaptic plasticity and glutamate signaling.

We have demonstrated metabolic markers in CSF associated with the classification of SMA in children, including 4-chlorophenylacetic acid, sodium dodecyl benzenesulfonate, and cinobufagin. We also identified the metabolic pathways associated with the severity of SMA, including lysine degradation, arginine metabolism, and tyrosine metabolism.

Motor susceptibility in patients with generalized tonic-clonic seizures.

Deubiquitinase USP19 directly interacts with and deubiquitinates MGMT, which repairs the DNA methylation damage response. USP19 plays a critical role in DNA methylation damage repair and temozolomide treatment for GBM patients.

C/EBPβ overexpression exacerbates the pathologic progression of AD, primarily by promoting neuroinflammation and mediating transcriptional regulation of several disease-associated proteins, such as δ-secretase and APOE4. Additionally, C/EBPβ stimulates the upregulation of ANP32A and TRPC1, leading to elevated levels of phosphorylated Tau, while inhibiting the expression of FOXO, which is associated with genes involved in longevity. The in-depth research of the pathway through which C/EBPβ regulates the development of AD also reveals multiple vicious cycle pathways between C/EBPβ overexpression and the pathological progression of AD.

This retrospective cohort study investigated the tolerability and efficacy of Anlotinib combined with the Stupp regimen for patients with H3K27M mutant diffuse midline glioma (DMG). Beyond establishing the safety profile, our study also identified encouraging benefits associated with Anlotinib treatment, particularly for patients with infratentorial DMG. These findings suggest that Anlotinib may represent a promising treatment option for H3K27M mutant DMG in the clinical setting.

An increase in synaptic connectivity between each of the brain areas (perirhinal cortex is shown graph as an example) that are interconnected with ventral pathway circuits and ventral pathway circuits produces object recognition memory (ORM) enhancement and causes a reversal ORM deficit.

Anxious behavior in mice with colitis was associated with an imbalance in hippocampal excitatory inhibition due to the overactivation of glutamate synapses. Peripheral suppression of colon inflammation or downregulation of GRM1 expression by AAV virus interference can significantly improve anxiety-like behavior.

CircRNA–miRNA–mRNA networks in epilepsy. CirRNAs can bind to microRNA response elements through sponging and regulate their expression downstream according to the competitive endogenous RNA hypothesis (ceRNA). The circRNA–miRNA–mRNA axes hold potential as valuable tools for comprehending the pathogenesis, diagnosis, and treatment of epilepsy. We summarize the possible regulatory networks of circRNA–miRNA–mRNA in epilepsy.