Cover image: The cover image is based on the article Examining the Impact of Microglia on Ischemic Stroke With an Emphasis on the Metabolism of Immune Cells by Xufeng Tao et al., https://doi.org/10.1111/cns.70229.

The clinical spectrum of GAD65 autoimmune neurological diseases appeared highly diverse. Immunotherapy can benefit the majority of patients, and early treatment appeared to be associated with good prognosis. RTX may be more effective than MMF; however, this requires more rigorous prospective studies to explore.

A proposed schematic model: phosphorylation of Tyr23 on Anxa2 mediates lncRNA-MEG3 inhibition-induced neuroprotection by interacting with pSer473-Akt in mitochondria.

Using an innovative genetic tool coupled with FACS and RNAseq, we identified Pla1a and Cox4i2 as two genes selectively enriched in brain pericytes compared to vascular smooth muscle cells.

This study demonstrates that the DTI-ALPS index, which reflects glymphatic functionality, is significantly diminished on the ipsilateral side in patients with acute spontaneous intracerebral hemorrhage. Lower DTI-ALPS values are associated with increased volumes of hemorrhage and edema as well as poor clinical outcomes at 90 days.

This research disclosed that ischemic stroke caused sensory motor deficits and different degrees of brain tissue damage in both young and aged rats, accompanied by disturbances in melatonin secretion, elevated cortisol levels, and disruptions in the sleep-awakening cycle and the expression of circadian rhythm-related genes Per1 and Cry1. In the future, further exploration of these issues and mechanisms will be conducted, thereby providing treatment ideas for related diseases.

Altered resting-state brain function, along with their spatial correlations to genetics and neurotransmitter systems, may associate with genetic vulnerability for schizophrenia.

Neuroinflammation and blood–brain barrier disruption play key roles in the progression of vascular dementia, and necroptosis is closely associated with vascular dementia. This review guides the prevention and treatment of vascular dementia by discussing the tumor necrosis factor-α signaling pathway, destruction of endothelial cells, glial cells, and oxidative stress and mitochondrial dysfunction in the presence of necroptosis. Inhibition of necroptosis may be useful in the treatment of vascular dementia to unfold a new world.

Different types of simple congenital heart diseases showed significantly different risks of epilepsy. Patients with patent foramen ovale had a significantly higher risk of epilepsy than those with other simple congenital heart disease types. Patients who underwent surgery for congenital heart disease had a lower risk of epilepsy than those who did not. PFO closure may have a significant effect on reducing the risk of epilepsy.

Schematic illustration of glia–neuron interactions in the spinal cord dorsal horn in bone cancer pain. NFAT1 is upregulated in spinal microglia in Lewis lung carcinoma-induced bone cancer pain. Upon activation, microglia synthesize and release IL-18 through p38 MAPK phosphorylation, leading to enhanced activation of the NMDA receptor and the subsequent Ca²⁺−dependent signaling in the dorsal horn.

Following spinal cord injury, microglia shift into the “activated” and “proliferative” state. Glycolytic reprogramming triggers H4K12 lactylation, which upregulates the transcription of Spp1. SPP1 protein is subsequently released to facilitate intercellular communication.

The AST activates the Nrf2/GPX4 signaling pathway to regulate glutathione metabolism and inhibit ferroptosis to preventing epileptic seizures.

In the mouse hippocampus, intermittent hypoxia altered the expression of many miRNAs, including miR-448-3p and miR-1264-3p. miR-448-3p and miR-1264-3p could influence the localization of hnRNPA2B1 by regulating the target gene Fam76b. As a splicing factor, hnRNPA2B1 may be involved in the response to intermittent hypoxia by regulating the ratio of Nbr1 and Dph3 transcripts.

The distinct neural electrophysiological patterns in the PD and LID states. The abnormal functional connectivity and information flow direction in PD state. The cumulative effects of chronic l-dopa administration on functional connectivity and information flow direction in LID states. The potential mechanism of tetrabenazine's amelioration of dyskinesia at the electrophysiological level in rats.

A SORBS2 gene variant (c.566C>T, p.T189M) was identified in an EOAD family. Overexpression of SORBS2 T189M variant in a murine model activated microglia, up-regulated inflammatory cytokines, induced neuroinflammation, exacerbated Aβ accumulation, accelerated neurodegeneration, and ultimately led to cognitive impairment. These results suggest that SORBS2 T189M variant is pathogenic in AD.

Sirtuin 1 (Sirt1), a key NAD⁺-dependent deacetylase, has become a leading therapeutic target for spinal cord injury (SCI) repair due to its regulation of multiple pathological processes, including inflammation, oxidative stress, and cell death. Sirt1 not only protects and regenerates neurons but also modulates astrocytes, microglia, oligodendrocytes, and vascular endothelial cells to optimize the SCI microenvironment. However, its regulatory mechanisms are intricate, varying based on activation timing, expression levels, and cell types.

¹⁸F-DPA-714 PET/MRI can effectively complement conventional MRI in the preoperative assessment of refractory epilepsy, with localization accuracy on par with ¹⁸F-FDG and enhanced capability in delineating lesion boundaries.

BBR exerts promising protection against KA-induced epileptic seizures through remodeling gut microbiota to regulate lipid metabolism in the colon and hippocampus.

RF maintains the BBB integrity following ischemic stroke by reducing neutrophil infiltration and the subsequent release of MMP9, thereby alleviating both neurological and histological impairments.

Our study showed that mitral E/A ratio was associated with nonhemorrhagic cerebral small vessel disease (CSVD). Left ventricular diastolic dysfunction assessed by transthoracic echocardiogram provides clues for the early warning of high burden of CSVD.

Cross-species analysis was used to identify novel pain mediators based on human DRG expression profiles and RNA-seq data from a mouse model of neuropathic pain injury.

Antiplatelet drugs are essential for treating atherosclerotic vascular disease (ASVD), but drug interactions can lead to resistance and affect therapeutic efficacy. Due to the complexity of treatments in ASVD patients, understanding these interactions is critical for optimizing therapy and reducing adverse effects. This article examines the clinical implications of these interactions and highlights potential research directions for individualized antiplatelet strategies.

Low-frequency stimulation (LFS) at VMH alleviated seizure severities across models. VMH LFS also retarded the epileptogenesis in the hippocampal-kindling model. LFS attenuated the activation of the glutamatergic neurons in VMH during seizures.

This review comprehensively examined the pathogenic genes associated with various NCL subtypes, elucidating their roles, clinical presentations, corresponding mouse models, and the advances in clinical study of potential therapeutics. In particular, we clarified the potential of novel microglial cell replacement therapies in NCLs, providing hope for slowing or halting disease progression.

Fecal microbiota transplantation modified the gut microbiota composition in 5 × FAD mice, resulting in decreased gut microbial-derived lipopolysaccharide. This alteration subsequently enhanced the cognitive function of 5 × FAD mice by inhibiting the hippocampal TLR4-IKKβ-NF-κB signaling pathway.

Hereditary spastic paraplegia (HSP) is a group of rare genetic neurodegenerative disorders. This review comprehensively outlines the clinical manifestations, gene expression trajectories, and protein function of HSP subtypes from the perspective of neurodevelopment. Insights into the early developmental mechanism underlying HSP may ultimately enhance the understanding of this disease and lead to the discovery of novel treatments.

This study found shared and age-specific brain functional network alterations after sleep deprivation compared to normal sleep conditions. Additionally, these age-specific abnormal connectivity patterns correlate with the spatial distribution of specific cognitive processes and specific genes related to signal transduction, ion channels, and immune signaling.

This study investigated the effects of 8 weeks of pretreatment with coenzyme Q10 (CoQ10) and high-intensity interval training (HIIT) alone and in combination on FNDC5, irisin, BDNF, and amyloid-beta (Aβ) plaque formation in the hippocampus of Aβ-related AD rats. Pretreatment with CoQ10 and HIIT improved the Aβ-induced reduction in BDNF levels probably through the FNDC5/irisin pathway and preventing Aβ plaque formation.

After ischemic stroke, resting microglia transform into pro-inflammatory or anti-inflammatory microglia under different conditions, respectively. Moreover, microglia respond to the environment by flexibly reprogramming intracellular metabolic pathways, thereby altering immune function, which mainly includes glucose metabolism, lipid metabolism, and amino acid metabolism.

Preoperative high D-dimer but low PTA level were the independent predictors of 3 months' unfavorable prognosis for AIS-LVO after calibration of confounders. Elevated admission D-dimer (≥ 715 mg/L) and reduced PTA levels (< 85.5%) are independent predictors of poor prognosis for patients with AIS-LVO, and there is a synergistic interaction between the two variables with higher odds ratio (aOR = 4.55, 95% CI 2.63–7.69).

Control groups (represented by green dots) and patients (represented by red dots) are separated by convex polygon decision boundaries. The solid line represents the classifier, the dashed line represents the boundary, and the red highlighted solid line portion represents the convex polygon used to separate the patient from the control group.

CD24 may be a potential innovative target of ischemic stroke for alleviating neuroinflammation via NF-κB pathway and Src pathway. The treatment of SPRC on ischemic stroke is associated with CD24 via CBS/H₂S pathway.

By integrating DNA methylation and gene expression from patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP), this study identified DAB2IP and SMYD3 as candidate genes potentially involved in DEACMP pathogenesis. Additionally, further evidence for their potential as DEACMP targets was provided through pyrosequencing and DEACMP rat model.

Increased functional activity of the fronto-parietal network (FPN) and language network (LN) might be involved in the pathogenetic mechanisms of bipolar disorder (BD). After treatment, baseline FCs were partially normalized, highlighting potential therapeutic mechanisms. Our neuroimaging–transcription analysis revealed genes and candidate pathophysiological processes associated with BD.

Osteopontin (OPN) is secreted by activated microglia, astrocytes, and infiltrating immune cells. OPN exhibits dual roles in Alzheimer's disease (AD), acting as a double-edged sword with both protective and detrimental effects. OPN contributes to AD progression through mechanisms leading to synaptic pruning, microglial activation, innate immune system activation, and chemotactic signaling. Conversely, OPN under certain conditions plays a protective role by maintaining synaptic integrity, facilitating vascular amyloid-beta (Aβ) clearance, and activating microglia to enhance Aβ clearance.

Morellic acid (MOR) alone, dose-dependently, and with the standard drug diazepam (DZP), significantly (p < 0.05) reduced the locomotive activities of Swiss mice. Additionally, the computational studies suggest that MOR exhibited the highest binding scores of −9.2 and −7.6 kcal/mol towards the GABA_A receptor α₃ and α₂ subunits, respectively.

In this study, we demonstrated that panaxadiol alleviated oxidative stress damage in mouse brain tissue caused by CIRI through the regulation of the JAK3/STAT3/HIF-1α signaling pathway. This study provided a theoretical basis and promising prospects for the clinical application of panaxadiol in the treatment of CIRI.

We explored the regulatory impacts and mechanisms of H₂S on SZ at multiple levels in human, cellular, and animal models. Our findings indicated that H₂S levels were significantly decreased in SZ patients and SZ model rats. Exogenous H₂S supplementation might alleviate schizophrenia-like behaviors by inhibiting apoptosis through S-sulfhydrylation modification. The graphic abstract is drawn By Figdraw.

The study identifies Ntoco as a critical regulator of ferroptosis in traumatic brain injury (TBI). Ntoco knockdown alleviates neuronal damage, while its overexpression exacerbates ferroptosis. This research highlights targeting Ntoco as a potential therapeutic strategy for reducing ferroptosis-induced damage in TBI.

PSP patients are characterized by a remarkably decreased ALPS-index, tau accumulation, dopaminergic dysfunction, and abnormal glucose metabolism in the brain. The glymphatic dysfunction is associated with tau deposition and abnormal metabolic brain network activity and is independent of dopaminergic impairment in PSP.

By recording neuronal activity from the primary somatosensory cortex and motor cortex simultaneously, during dexmedetomidine (DEX)-induced anesthesia or sleep, we investigated the cortical response and oscillation properties across different brain areas. Correlation analysis between single neuron activity and LFP power indicates that more neurons were correlated, either positively or negatively, with LFPs during DEX-induced anesthesia compared to sleep.

NONHSAT141192.2 upregulates the expression of SOX2 and PIK3R3 by sponging miR-4279, influencing GSC characteristics and their resistance to radiation.

Prolonged exposure to IL-1β impairs cognitive flexibility in animals, evidenced by poor performance in the Barnes maze reversal phase. Mice with cognitive resilience show increased neuronal excitability in the dCA3. Activation of CA3 pyramidal neurons improves cognitive flexibility, while inhibition reproduces the cognitive inflexibility linked to IL-1β administration.

The Metrnl-attenuated neuronal ferroptosis via the activation of C-KIT/AMPK/Nrf2 signaling pathway after SAH.

Combining function-specific SMA-targeted cTBS with standard treatment may be more effective than conventional SMA targeting in accelerating the onset of clinical efficacy in TS treatment.

Our study is the first to investigate the combined use of melatonin and luzindole for intracerebral hemorrhage-induced adverse events. Melatonin alleviated glymphatic system dysfunction and blood–brain barrier damage, facilitated hematoma absorption and edema resolution, and mitigated cognitive-behavioral deficits, while luzindole partially reversed these effects. This effect may be related to circadian rhythms.

Graphical abstract showed that loss-of-function of LncRNA-Vof16 (abbreviated as Vof16) aggravates neuronal hyperexcitability and hyperalgesia induced by spared nerve injury. On the contrary, gain-of-function of Vof16 holds the opposite and protective effects.

XCHT alleviates depression by anti-neuroinflammation and rebalancing the HPA axis, neurotransmitter release, and tryptophan metabolic pathway. Meanwhile, XCHT promotes neurogenesis by up-regulating the BDNF/PI3K/AKT signaling pathway, resulting in harmonizing the neuroendocrine network.

This study used Mendelian randomization analysis to explore the causal link between physical activity and various symptoms in the progression of Parkinson's disease. This findings suggested that genetically predicted physical activity engagement exhibited the potential to lower constipation risk and UPDRS2 scores, informing potential PA recommendations for Parkinson's disease management.

The study observed that both physical frailty and poor sleep were significantly and linearly associated with a higher risk of incident delirium. Achieving healthy sleep could not only lower the risk of delirium but also greatly offset the adverse impact of frailty on delirium.

Sketch of Cas9 transgenic mouse model for skull base meningioma.

Adeno-associated virus (AAV) vector pAAVCre/gRNA was introduced into the meningeal cells of the Cas9 mouse skull base. Cas9 functions were activated by Cre in these cells and caused mutations of the four genes (Nf2, P15Ink4b, P16Ink4a, and P19Arf) in meningeal cells, which could lead to tumorigenesis of meningioma in the skull base of Cas9 mice.

The expression profiles of piRNAs in CA1 were significantly changed after tGCI. HPC down-regulated the expressions of the top 5 piRNAs associated with synaptic function, including rno_piR_000618, rno_piR_009428, rno_piR_017990, rno_piR_014971, and rno_piR_011022 induced by tGCI. Down-regulation of rno_piR_011022 mediated by HPC enhanced synaptic plasticity through inhibiting the NR2B-PSD95 interaction, thus ameliorating ischemic neuronal injury and improving the learning and memory functions of rats.

The study identifies the critical role of the CCL17/CCR4 axis in microglial polarization and hematoma clearance following intracerebral hemorrhage. By activating the ERK/AP1/SRA signaling pathway, CCL17/CCR4 enhances neuroprotection and functional recovery, providing a potential therapeutic target for improving outcomes in stroke patients.

Using C. elegans as a model organism, we scrutinized the effects of FAEW on pathogen avoidance behaviors via the gut-germline-neural signaling. Demonstrating for the first time that FAEW prevents avoidance behavior through gut-germline-neural signaling, inhibition of H4K8 acetylation, and activation of DAF-16.

We identified and validated 25 causal protein targets linked to Parkinson's disease (PD) onset and progression using proteomic and genetic analyses. Using plasma and brain large-scale pQTL datasets, we conducted proteome-wide association studies (PWAS) and Mendelian randomization (MR) to assess causality. Our findings revealed 16 plasma proteins associated with PD progression and 9 with PD onset. Notably, GPNMB was implicated in both. Our study provides new insights for PD therapeutic strategies.

Meth downregulates PARL expression, which in turn causes the aberrant cleavage of PINK1 and PGAM5. The increased PGAM5 level ultimately triggers the recruitment of p-MLKL on the mitochondrial membrane to form pores that disrupt mitochondrial homeostasis, ultimately triggering excessive mitophagy and necroptosis.

Prenatal VPA exposure during the neurogenic period impaired the cognition of the offspring by disrupting interneuron migration and differentiation. The influence of VPA was found to be subtype-specific, predominantly affecting the somatostatin-positive neurons.

Inhalation of 67% hydrogen gas exerts a protective effect on sepsis-associated encephalopathy, effectively improving the survival rate of septic mice, protecting cognitive function, and reducing tau protein phosphorylation. The mechanism may involve hydrogen enhancing PINK1/Parkin-mediated mitophagy, which inhibits the activity of the cGAS-STING-IRF3 pathway, thereby reducing neuroinflammation.