Cover image: The cover image is based on the article Lycium barbarum Extract Enhanced Neuroplasticity and Functional Recovery in 5xFAD Mice via Modulating Microglial Status of the Central Nervous System by Zhongqing Sun et al., https://doi.org/10.1111/cns.70123.

This study illustrates that PTP1B induces disruption in endocytosis and apoptosis of VSMCs through the Rab5-PDGFRβ pathway, suggesting a potential association with the heightened vulnerability of carotid plaques. Our results also present novel evidence supporting the potential use of PTP1B inhibitors in the treatment of vulnerable carotid plaques.

Outcomes from this study provide supportive evidence in favor of probiotic-rich supplementation as an adjunctive therapy with existing antiseizure medications as these commensal bacteria might provide prophylaxis against intractable seizures, particularly in predisposed individuals.

This study constructed a prognostic model for mitochondria and macrophage polarization correlation in glioma based on single-cell and transcriptome sequencing. Five genes associated with the prognosis of glioma (ECI2, MCCC2, OXCT1, SUCLG2, and CPT2) were revealed and then, validated using glioma tissues, providing novel insights into individualized treatment and prognosis.

We recruited 50 healthy volunteers for two sleep deprivation experiments. In Experiment 1, each participant underwent a psychomotor vigilance task under three conditions: (1) after normal sleep, (2) after 30 h of sleep deprivation, and (3) after a subsequent 30-min nap, while undergoing functional magnetic resonance imaging (fMRI). By analyzing the dynamic changes in task performance and brain responses across these conditions, we aimed to identify the optimal stimulation target. We discovered, for the first time, that the brain response in the right middle frontal gyrus exhibited the least recovery after a nap, leading us to select it as the stimulation target. In Experiment 2, using the same protocol (normal sleep, 30 h of sleep deprivation, 30-min nap), rTMS stimulation was applied after the nap. Subsequently, we found that individualized rTMS attenuated the sustained attention decline induced by sleep deprivation relative to napping alone. Thus, nap combined with personalized rTMS may facilitate the recovery of sustained attention following sleep deprivation by modulating neural activity in brain functional networks.

This study shows that ginsenoside Rg1 induces the activation of PI3K/AKT pathway through the lncRNA-Malat1/miR-124-3p/Lamc1 axis, which is vital in controlling AS function and revealing new regulatory pathways implicated in the repair of SCI.

Anesthesia and surgery increase the calcium concentration in the hippocampus, increasing the phosphorylation of Camk2. Anesthesia and surgery activate the Radixin pathway, leading to increased phosphorylation of Radixin. The activation of these two pathways results in increased surface expression of α5GABAARs, ultimately leading to hippocampus-dependent memory impairment. Preadministration of the neuroprotective drug fasudil can inhibit the phosphorylation of the key molecules mentioned above, prevent the translocation of α5GABAARs to the cell surface, and thereby mitigate neurocognitive damage.

Because of CSF biomarkers identified by neuroimaging techniques in the middle or late stages of AD, blood is considered as the novel biomarker resource for the early diagnosis of AD. The accurate alternations in blood could predict AD. This paper discusses potential blood-based biomarkers identified by proteomics and metabolomics and future research direction for AD prediction, and provide an overview of early diagnosis and even promising therapeutic approaches for AD.

This graphic abstract provides an overview of the paper, focusing on the neuromodulatory effects of the neuropeptide orexin-A (OXA) in sepsis-associated encephalopathy. OXA reduces reactive oxygen species-induced oxidative stress by inhibiting NOX2 expression in hippocampal tissue. The main mechanism may be by inhibiting the activation of A1-type astrocytes and microglia with the NF-κB/ERK signaling pathway, which reduces the expression of pro-inflammatory factors TNF-α and IL-1β and reduces neuronal apoptosis.

During excitotoxicity, reactive oxygen species, produced by NADPH-oxidase 2 (NOX-2), increases the levels of aquaporin-4 (AQP4) leading to the rupture of the blood–brain barrier and cerebral edema. This along with oxidative stress contributes to neuronal death. Stimulation of cannabinoid receptor type 1 receptors relieves oxidative stress by a reduction of NOX-2 activity and thus inhibits AQP4 increase, edema, and brain damage. The endocannabinoid system can be a therapeutic target for limiting brain damage.

Intermittent and continuous theta burst stimulation were used to stimulate ipsilesional and contralesional hemisphere, respectively, during the subacute phase after stroke. Rs-fMRI was used to detect neuronal activity and functional connectivity, and immunohistochemistry was used to verify the results of rs-fMRI.

Our findings suggest that PPAR-γ regulates microglial activation/polarization as well as subsequent neuroinflammation/oxidative stress via the HMGB1/NF-κB and NRF2 signaling pathway, thereby contributing to myelination and amelioration of WMI after HI insult in neonatal mice.

Border-associated macrophages (BAMs) are integral to the maintenance of brain homeostasis and the immune response to pathological conditions. This review addresses the ontogeny, replenishment, and microenvironmental regulation and transcriptomic heterogeneity of BAMs. Additionally, the roles of BAMs in sustaining brain homeostasis, conducting immune surveillance, and mediating responses to injury and neurodegenerative processes are critically examined.

This case report provides the first evidence that coenzyme Q10 may improve muscle weakness in patients with 22q11.2DS. The patient's genetic copy number deletion mutation region mainly contains COMT, PRODH functional genes related with mitochondria dynamics. The level of L-arginine was significantly increased after treatment by coenzyme Q10 in serum.

Myeloperoxidase activity is increased in X-linked dystonia parkinsonism (XDP) postmortem brain and caused an increase in oxidative stress. Decreasing MPO levels or inhibiting its activity significantly reduced reactive oxygen species in vitro, suggesting that targeting MPO may reduce oxidative stress in XDP.

The schematic diagram of TIP60 alleviates cognitive impairment and neurological damage in AD by activating SNAP23-mediated autophagosome-lysosome fusion through activating SOX4/IKKβ signaling.

In a cohort of patients with extensive-stage small cell lung cancer undergoing immunotherapy, this study explored the role of radiotherapy and delve into brain metastases subgroup. Brain and thoracic radiotherapy were identified as favorable prognostic factors for survival in those with brain metastases. Moreover, prophylactic cranial irradiation and thoracic radiotherapy delayed intracranial progression in those initially without brain metastases. These findings underscore the pivotal role of local therapies in the management of extensive-stage small cell lung cancer during the immunotherapy era.

SYS18 has a certain therapeutic effect on acetic acid–induced acute inflammation. It protects the BBB integrity by decreasing the BBB permeability, inhibiting endothelial glycocalyx degradation, and regulating TJs and MMP-9 expression levels in AIS. SYS18 can alleviate neurological impairment by inhibiting inflammation and protecting the BBB integrity in AIS.

The microbiota–gut–brain axis plays an important role in the development of Alzheimer's disease (AD). In terms of treatment, it has been proven that traditional Chinese medicine are effective in AD by regulating the gut microbiota. And then gut microbiota and its metabolism may inhibit inflammatory response through tumor necrosis factor-α (TNF-α), interleukin (IL), the nuclear factor kappa-B pathway, and superoxide dismutase metabolism. The sedimentation of β-amyloid (Aβ) and learning and memory function of AD are finally influenced. It indicates that choosing appropriate Chinese medicine as the complementary treatment may be a better way to achieve satisfactory clinical efficacy in AD.

Local neuronal activity and the hippocampal functional network of rsfMRI can predict the recovery of consciousness at 3 months post-onset in individuals with aDOC caused by neurological injury.

Somatic symptoms are common manifestations in MDD patients. However, there is a lack of research on tDCS for treating somatic symptoms in MDD. This study found tDCS targeting DLPFC significantly improved somatic symptoms in MDD patients, suggesting it an effective target of tDCS for somatic symptoms in MDD.

Hand-motor-related cortex on the lesional hemisphere (A4ul_L) increasing its nodal efficiency in postoperation was beneficial for SMA syndrome recovery. The A4ul_L may be a potential therapeutic target for SMA syndrome. Applying nrTMS with high-frequency stimulation on the node A4ul_L will increase its nodal efficiency, but sham-nrTMS won't. It may indicate that nrTMS stimulation may accelerate SMA syndrome recovery.

Inter-network functional connectivity of the orbital part of the right superior frontal gyrus and left supplementary motor area mediated the relationship between self-regulation and depression. Self-regulation could impact depressive symptoms via regulating inter-network functional connectivity of thalamic subnuclei. Thalamic functional subnetworks could predict the self-regulation and depressive severity of depressed individuals.

We first compared the DFNC and SFNC of the three networks and examined their associations with tremor symptoms. PIGD-PD patients were more likely to remain in the condition of sparse connection. The enhanced connection between the cerebellum and cognitive networks is considered a type of dynamic compensation.

ASOs have led to important advancements in mRNA regulation for treating developmental and epileptic encephalopathies (DEEs). The mechanisms of action may vary: RNA function blocking could be obtained by modulating alternative splicing or through steric hindrance; similarly, RNA degradation could be obtained through RNase H1. However, upregulation of the final haploinsufficient protein product can also be achieved. Pre and clinical studies pave the way for potential innovative therapies.

Our study aims to automatically classify and segment CT images of patients with traumatic brain injury using a deep learning model. Based on the automatic classification and segmentation, volume and subtype characteristics of the hematoma were extracted and combined with other clinical information to predict in-hospital mortality.

After a stroke, multiple pathways in the neurohumoral system are activated. At the same time, the blood–brain barrier is compromised, and pro-inflammatory substances are released from the brain into the bloodstream, consequently activating the peripheral inflammatory immune response. As an acute injury, stroke triggers renal hemodynamic disturbances and an acute ischemic state in the kidney, thereby promoting the development of AKI or CKD.

PLD4 is upregulated in CPZ-induced MS and modulates microglial phagocytosis and remyelination via the AKT pathway. PLD4 deficiency resulted in inhibition of microglial phagocytosis of myelin debris and impaired remyelination in the corpus callosum.

Blood–brain barrier (BBB) works as a crucial structure separating central nervous system (CNS) and circulating system. The highly organized endothelial junctions and transporters strictly restricts substance exchange across BBB to maintain the homeostasis of CNS. In Alzheimer's disease, BBB breakdown has been widely detected, featured as a series of brain endothelial cell (BEC) pathologies, including increased permeability, abnormal levels and functions of influx and efflux transporters, as well as inflammatory and oxidative profile. The goal for BEC-targeting treatment in AD is to maintain the integrity of BBB and accelerate the clearance of brain-derived Aβ species through BBB. BEC-targeting treatment for AD mainly focuses on regulating a series of pathological processes including inflammation, oxidative stress, autophagy, apoptosis, and several signaling such as angiogenic and Wnt/β-catenin pathway, as well as modulating Aβ clearance pathway and so on. Targeting various BEC pathologies have shown therapeutic potentials in protecting BBB and improving cognitive functions in AD.

The NLRP3 inflammasome exhibited a strong correlation with neurological injury in severe CVT, both in rats and patients. The neuroprotective benefits of steroid treatment in severe CVT-associated brain injury were possibly attributed to its ability to suppress NLRP3 inflammasome-induced inflammation.

On the basis of oncolytic adenovirus TS-2021 infection caused PARP activation. The combination of TS-2021 and olaparib increases virus titer, p66shc phosphorylation, reactive oxygen species production, and DNA damage, leading to synergistic apoptosis in GBM.

The newly developed dual-wavelength dual-output MRgLITT system LaserRO within two probe trajectories in treating drug-resistant epilepsy patients.

Dl-PHPB and puerarin inhibit the Gq-PLC-IP₃-Ca²⁺ signal transduction pathway, reduce IP₃ and intracellular [Ca²⁺]_i and decrease platelet aggregation via acting on P2Y₁ receptor. However, salvianolic acid B, like ticagrelor, inhibits the Gi-AC-cAMP signal transduction pathway, enhances cAMP and decreases platelet aggregation via acting on P2Y₁₂.

The schematic diagram showing the 9-MF prevented long-term cognitive impairments via cell-specific inhibition of ROCK2 and GSK3β in APP/PS1 transgenic mice.

mDA cells exposed to the tumor microenvironment induced abnormal proliferation in vitro and in vivo, which was ascribed to the hyperactivation of proliferation-related genes, the JAK/STAT3 pathway, and cytokine stimulation. It suggests that exposing functional progenitors to the TME offers a novel strategy to improve the sensitivity of tumorigenicity study.

LBE administration preserved cognition, movement, and visual function in 5xFAD mice. It reversed systemic inflammation and reduced Aβ load by enhancing microglial phagocytosis through modulating microglia into a neuroprotective state, thereby ameliorating the neurological pathology of the CNS (brain, spinal cord, and retina).

Hsa_circ_0015335 mediate DHCR24 levels may facilitate cognitive impairment of cerebral small vessel disease through affecting brain cholesterol metabolism and brain structure changes.

Our two-sample Mendelian randomization analysis suggested that except waist circumference, higher body mass index (BMI), body fat percentage, body fat mass, and hip circumference were protective against Parkinson disease (PD), and were more pronounced in females than in males. Colocalization analysis highlighted two colocalized regions shared by BMI and PD. Cross-trait meta-analysis successfully identified 10 novel genomic loci. They pointed to some genes as possible players, including SRGAP3, MTMR14, ADORA2B, TOX3, and MAP4K4. Enrichment analysis showed that BMI-associated genetic variants were enriched in multiple brain tissues.

This is the first-in-human dose-escalation Phase I study of BAT4406F, a fully humanized anti-CD20 monoclonal antibody with enhanced ADCC effect. The safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and preliminary efficacy of BAT4406F injection on Chinese neuromyelitis optica spectrum disorder (NMOSD) patients were investigated.

Schematic diagram of methodology. (A) T1-weighted image of each subject was parcellated into 322 cortical and subcortical regions, and gray matter volume of each region was computed by Freesurfer. Then regional case–control differences were estimated. (B) Gene expression profiles of each region (left hemisphere only) were extracted from AHBA database and obtained 159 × 15,633 regional gene matrix. (C) PLS regression was applied to link case–control t-values and gene expression data. Then, pathway enrichment analysis and cell type assignment were conducted on the gene list of first component of PLS to identify different biological pathway and cell types between groups. Additionally, the GABAergic atlas was used to explore the relationship between inhibitory neurotransmitter and morphometric alterations. AHBA, Allen Human Brain Atlas; PLS, partial least squares.

FTS through inhibiting Gal-3 reduces the expression of TLR4 and CD14, alleviates Aβ pathology, and downregulates Aβ-stimulated TLR2, TLR4 and CD14 expression, and thus alleviates neuroinflammation in Aβ_1–42 mice.

DRN serotonergic afferent activity in the VTA are wake active. Upregulation of DRN serotonergic terminals in the VTA induced wake from sleep. Dynamic VTA dopaminergic, glutamatergic, and GABAergic neuronal firing changes respond to the wake-promoting effect of DRN serotonergic afferents.

RNF2 was upregulated in the ischemia–reperfusion brain, as well as in nerve cells treated with OGD/R or TM. RNF2 inhibited cell apoptosis. RNF2 promoted MANF nuclear transport. RNF2 monoubiquitinated MANF and stabilized MANF protein level. RNF2 inhibits cell apoptosis dependently on MANF, which can be reversed by recombinant human MANF.

Our study uses energy landscape analysis to investigate the brain dynamics of patients with major depression (MDDs) under task conditions. The experiments show that brain networks in MDDs show more restraint and less freedom, which is associated with depressive symptoms such as negative emotional bias and rumination.