The cover image is based on the article High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics by Yan Cui et al., https://doi.org/10.1111/cns.70021.

The cover image is based on the article Transcranial direct current stimulation enhances the protective effect of isoflurane preconditioning on cerebral ischemia/reperfusion injury: A new mechanism associated with the nuclear protein Akirin2 by Xiangyi Kong et al., https://doi.org/10.1111/cns.70033.

The complexity of gliomas, including challenges like blood–brain barrier (BBB) breakdown, tumor heterogeneity, and immune evasion, can be addressed through the development of glioma vaccines. These vaccines aim to enhance the immune system's ability to recognize and target tumor-associated antigens, leading to a more effective antitumor response. The various vaccine strategies—dendritic cell-based, peptide-based, and viral vector-based—are discussed, along with their potential in overcoming the limitations of traditional therapies.

Parkinson's disease (PD) is characterized by neuron degeneration and diverse symptoms, posing diagnostic challenges. Plasma netrin-1 (NTN-1) emerges as a potential biomarker for early detection. A study with 105 PD patients and 65 controls shows lower NTN-1 levels in PD, correlating with symptom severity and demographic factors.

Induction of DNA oxidative damage, PARP-1 overactivation, and subsequent NAD⁺ depletion were proved to be crucial events in the pathogenesis of PINP. Specific inhibition of PARP-1 enhanced mitochondrial redox metabolism partly by upregulating the expression and deacetylase activity of SIRT3 in the PINP rats.

Due to the downregulation of GLT-1 expression in hippocampal astrocytes caused by diabetes, the increased excitability of glutamatergic neurons induced by anesthesia/surgery was amplified in the local hippocampal, which led to oxidative stress, apoptosis, and finally cognitive dysfunction.

In the acute phase of spinal cord injury, glycolysis is weakened, and at the same time, lactic acid modification is weakened. After lactate supplementation through exercise, lactylation is increased and the motor function of mice is improved.

In hippocampal neurons of ASD rats, elevated sortilin levels are associated with increased delivery of PGRN to lysosomes, where the endocytosed PGRN is rapidly degraded. This high level of sortilin, coupled with low PGRN expression, could result in the activation of microglia and the NF-κB pathway. The activation of the NF-κB pathway might further promote microglial activation. Collectively, these factors contribute to synaptic loss and a reduction in dendritic spines in the hippocampus, leading to autism-like behaviors.

Schematic diagram of the mechanism. RNF122 catalyzes the non-degradative ubiquitination modification of K63 of JAK2 and further promotes the phosphorylation activation of JAK2. Phosphorylated JAK2 then activates its downstream protein STAT3. The phosphorylated STAT3 enters the nucleus and promotes the transcriptional activation and protein expression level of c-Myc. As a common oncogenic protein, c-Myc can further promote the malignant progression of glioblastoma.

Iron accumulation mice model with ovariectomy could lead to the decline of movement and cognitive function. Iron accumulation could cause histopathological damage in the hippocampus of ovariectomized mice and, by disturbing hippocampus proteome, particularly the expression of hippocampal iron metabolism-related proteins, could further influence cognitive impairment in ovariectomized mice.

RIPC ameliorated brain edema induced by high-altitude hypoxia through stimulating glucose metabolism down to the TCA cycle to boost mitochondrial ATP production. This finding supports the potential of RIPC as a viable therapeutic approach for the prevention and treatment of HACE, targeting metabolic reprogramming. This figure was created with BioRender (https://www.biorender.com).

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder characterized by motor dysfunction and premature mortality. Luteolin, a natural flavonoid with known antioxidant and neuroprotective properties, has shown promise in various neurodegenerative diseases. This study aimed to evaluate the potential benefits of luteolin treatment in a mouse model of (HD). To assess the effects of luteolin treatment, HD N171 82Q transgenic mice received luteolin administration, while another group received a vehicle treatment for comparison. The mice's body weight changes and survival rates were monitored throughout the study. Additionally, they underwent a series of motor function tests, including the rotarod test, balance beam test, and limb clasping test. Immunohistochemical staining and western blotting were utilized to assess the localization and expression of huntingtin aggregates, respectively. Findings revealed a significant protective effect of luteolin treatment against premature mortality and prevented weight loss in HD mice compared to the non-luteolin-treated group. Furthermore, the luteolin-treated mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction-related manifestations, such as dystonic movements. Immunohistochemistry analysis and protein quantification demonstrated a decrease in the accumulation of huntingtin aggregates in the brain's cortex, hippocampus, and striatum of luteolin-treated mice compared to the vehicle-treated group. These findings collectively indicate that luteolin holds promise as a therapeutic agent for managing motor dysfunction, reducing huntingtin aggregations, and improving survival outcomes in individuals affected by Huntington's disease. The findings are of significance as currently, there are no approved therapeutic interventions that reverse HD pathology or slow down its progression.

Alzheimer's disease is recognized to be associated with dysregulation of lipid metabolism and abnormal tempo-spatial patterns of dynamic functional network connectivity. The dynamic connectivity represented a better power in differentiating Alzheimer's disease patients from non-Alzheimer's disease subjects than static connectivity. Differential connectivity of strong-connected state between APOE-ε4 carriers and non-carriers mediated the relationship between Apolipoprotein E-ε4 genotype and cerebrospinal fluid and cognitive indicators.

We reconstructed whole-brain structural connectivity (SC) and functional connectivity (FC) networks for severe cerebral small vessel disease (CSVD) burden patients (CSVD-s), CSVD mild burden patients (CSVD-m), and healthy controls. The CSVD-s group showed considerably decreased SC-FC coupling in the limbic/subcortical module compared with the CSVD-m group, while there was no difference in SC-FC coupling between the CSVD-m and control groups.

In the normal central nervous system, osteocalcin is involved in neuronal structure, neuroprotection, and the regulation of cognition and anxiety. Studies on osteocalcin-related abnormalities in the central nervous system are divided into animal model studies and human studies, depending on the subject. In humans, the link between osteocalcin and brain function is inconsistent. These conflicting data may be due to methodological inconsistencies. By reviewing the related literature on osteocalcin, some comorbidities of the bone and nervous system and future research directions related to osteocalcin are proposed.

In this work, we proposed that vascularized allogeneic spinal cord transplantation (vASCT) might offer a new surgical approach for treating spinal cord injury. In the vASCT surgical model, the combination of polyethylene glycol with tacrolimus demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. The safety and efficacy of vASCT were verified by behavioral evaluation, electrophysiological examination and imaging examination.

The study has provided that Levels of NLRP3, especially in the CSF on day 3 post-injury, could serve as a potential biomarker for predicting prognosis in moderate to severe TBI patients. Early measurement of NLRP3 levels could provide valuable insights into patient outcomes and guide therapeutic strategies.

Surgery for malformation of cortical development (MCD) in children with drug-resistant epilepsy shows 81.3% success. Early surgery, fewer pre-op anti-seizure medications predict better outcomes. Different ages in MCD patients show varied clinical traits.

Ferroptosis occurs during cerebral ischemia/reperfusion, resulting in cerebral injury. Rh-B4galt1 exerts neuroprotective effects by regulating ischemia-induced ferroptosis, which is mainly dependent on the heightening of the TAZ/Nrf2/HO-1 pathway. Thus, B4galt1 may be considered a novel potential therapeutic target for ischemic stroke treatment.

The Ginkgo biloba leaf extract (GBE) study demonstrates its promise as an Alzheimer's treatment, significantly improving cognitive function and neuronal morphology. The effects are mediated through modulation of the PI3K/AKT/NF-κB signaling pathway, which impacts inflammation and neuronal health, offering a potential new avenue for therapeutic intervention in neurodegenerative disorders.

Schematic of betulin/DJ-1/Akt/Nrf2 signaling pathway.

Here, we found that Piezo1 inhibition attenuated neuronal apoptosis and improved the outcome of neurological deficits in rats after subarachnoid hemorrhage. Activation of Piezo1 by intracranial hypertension induced neuronal apoptosis via activating the Hippo pathway in primary neurons. Furthermore, this study incorporated the variables of oxyhemoglobin and intracranial hypertension into the cultivation of neurons, resulting in a compounded impact on neuronal apoptosis.

Hypersynchrony (HYP) and low-voltage fast (LVF) rhythm are the two most common forms of onset in mesial temporal lobe epilepsy (MTLE). HYP onset often involve atrophy and hypometabolism of the ipsilateral hippocampus and amygdala, while LVF onset is mainly characterized by hypertrophy of the amygdala. Different SOPs also involve different pathology.

The protocol of exploring the safety, tolerability, effectiveness, and pharmacokinetic characteristics of Pyrenegabine tablets as an adjunctive treatment for focal epilepsy.

The mechanism of vestibular compensation.11 The MVN receive afferent signals from the peripheral vestibular system and other brain regions, such as the cerebellum, the neuronal activity is balanced between the bilateral vestibular nuclei. After the unilateral peripheral injury, this loss of afferent leads to down-regulation of neuronal activity in the ipsilateral vestibular nucleus, while up-regulation in the contralateral side. This imbalance is believed leading to the symptoms of vestibular disorders. CNS can partially rebalance the neural activity between bilateral MVN, and reverse the vestibular symptoms. In contrast to the ipsilateral side, the contralateral MVN neurons become more active, which might be due to the reduced inhibitory input from the ipsilateral vestibular nucleus. Besides the inhibitory commissural projections between the bilateral MVN, the cerebellum and other brain region inputs are also critical for vestibular compensation. Green dashed line with arrowheads: Excitatory transmission; Brown dashed line with arrowheads: Inhibitory transmission. CNS, Central nervous system; MVN, Medial Vestibular Nucleus.

High concentration (67%) of hydrogen gas inhalation exerts a protective effect on sepsis-associated encephalopathy, and the mechanism may be improving mitochondrial function through the promotion of mitochondrial biogenesis and the improvment of mitochondrial dynamics.

This multicenter study, which involved 1211 patients with type 2 diabetes, aimed to elucidate the correlation between coagulation function and the risk and severity of diabetic peripheral neuropathy (DPN). Among the coagulation parameters examined, fibrinogen was found to be independently associated with the risk (OR 1.172; p = 0.035) and severity of DPN (p < 0.05), and this finding was externally validated.

How could the cerebral perfusion response to fasting-postprandial metabolic switching in Alzheimer's Disease (AD)? Difference cerebral blood flow (ΔCBF) of arterial spin labeling imaging between fasting and postprandial states was used to reflect cerebral perfusion response to fasting-postprandial metabolic switching. AD participants had poor ability to maintain cerebral perfusion homeostasis; AD had lower ΔCBF values in the right anterior temporal lobe than mild cognitive impairment patients and healthy controls; ΔCBF in the anterior temporal lobe showed a negatively correlated with cognitive function in AD. ΔCBF in the anterior temporal lobe can be a potential radiological marker to reflect the cognitive function in fasting-postprandial metabolic switching in AD.

Transcranial direct current stimulation treatment alleviates oxidative stress and activates Akirin2-PTEN signaling pathway, and enhances the neuroprotective effect of isoflurane pretreatment on ischemic stroke, highlighting the potential of combination therapy for ischemic stroke.

Copper is an essential trace element in the human body, participating in a variety of biological functions and metabolic processes. The homeostatic copper in the human body is regulated by the absorption, transportation, storage, and metabolism of copper. Dysregulation of copper metabolism is closely related to the occurrence and progression of various diseases. The cell death induced by copper overload is initiated by interaction between copper and acylated enzymes in the tricarboxylic acid (TCA) cycle, which then results in protein aggregation, loss of iron-sulfur cluster proteins, and cell death. Furthermore, we discuss the role of copper in regulating autophagy, the relationship between copper-dependent death and disease, and the potential role of copper in cancer treatment. We emphasize the necessity for further research into alternative pathways of copper-induced cell death, the detailed mechanisms of Cuproptosis, and biomarkers for copper poisoning. It proposes future research directions, including exploring the molecular mechanisms of Cuproptosis, developing new therapeutic strategies, and verifying their safety and efficacy in clinical trials.

• Combined application of CLP290 and Bumetanide can effectively increase the ratio of KCC2/NKCC1, restore RDD levels, enhance GABA_A receptor-mediated inhibitory function in the spinal cord, and relieve neuropathic pain in SCI.
• Bumetanide significantly improves neuropathic pain in the long term, whereas CLP290 demonstrates a notable short-term effect.

Current knowledge suggests that autoimmune astrocytopathy primarily involves antibodies targeting AQP4 and GFAP. This study aimed to investigate a novel type of autoimmune astrocytopathy that is negative for both AQP4-IgG and GFAP-IgG and explore its clinical manifestations, biomarkers, and pathology.

Schematic diagram illustrating the potential mechanism by which the BLA^CaMKII-rACC neural circuit mediates mechanical allodynia and anxiety-like behaviors in SNI mice, as well as the analgesic and anxiolytic effects of EA.

Based on predictors that are routinely available, we provided an accurate and convenient diagnostic tool that can predict the clinical progression of mild cognitive impairment patients and identify Alzheimer's disease specific pathological changes. This tool may contribute to more precise clinical treatment and better health care resource allocation.

Anxiety often coexists with migraine, with both conditions sharing commonalities in oxidative/nitrosative stress and mitochondrial dysfunction contributing to their pathogenesis. In this study, we found β-sitosterol to reduce anxiety in migraine-induced rats, likely via its antioxidant and cellular metabolism enhancing effects.

This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms. ns not significant. *p < 0.05.

Dezocine is a partial MOR agonist previously used clinically in the USA and currently in China. It has been proposed that dezocine be reintroduced to clinical use in the USA, as an analgesia and/or an additional tool to treat opioid use disorder. To consider the clinical reintroduction of dezocine knowing its abuse liability is important. In this review, we found no reports of abuse, dependence or overdose in the English literature, and a small number of cases of dependence in the Chinese literature. If it is less or non-addictive than other opioids, its short half-life would allow it to bridge to other medication assisted therapies, facilitate tapering of opioid use and perhaps be used as a rescue medication in those trying to reduce opioid use.

The paraventricular nucleus regulates drug addiction directly by modulating reward and aversion systems or indirectly by affecting stress response and emotional regulation. In this process, the corticotropin-releasing factor, oxytocin, arginine vasopressin, rostral ventrolateral medulla, neuropeptide Y, agouti-related peptide, and pro-opiomelanocortin neurons are involved in the modulation of drug addiction.

KA-induced excitotoxicity leads to ferroptosis of neurons by activating ferritinophagy. 3-MA effectively inhibited KA-induced ferroptosis. KA activates ferritinophagy in neurons. Interference with NCOA4 effectively protects against neuronal damage caused by KA.

This study provided novel evidence that fNIR-derived biomarkers could early predict PSF risk that can be widely used in clinical practice. Meanwhile, this study demonstrated that the higher brain activation and inability to increase the brain functional connectivity in stroke patients during difficult task indicated the inefficient use of brain resources.

Exposure to high-altitude hypoxia impairs memory by reducing CIRP and GluR1 levels in neurons, affecting synapse integrity. Tat-C16 peptide administration ameliorates these impairments, suggesting a potential therapeutic strategy.

In this study, we revealed an inhibitory projection from LHA^GABA to LPAG facilitates arousal from sevoflurane, suggesting a complex control of wakefulness through intimate interactions between long-range connections. These findings enhance our understanding of the mechanisms of consciousness shift and potentially facilitate the development of studies involving the GABAergic system.

In this research we focused on the objective changes behind default mode network disruption induced by delirium-like behavior in aged rat induced by isoflurane anesthesia and tibia fracture fixation surgery. The study not only pointed out long-term changes in miRNA and target gene, but also improves interpretability and reproducibility of resting state functional magnetic resonance imaging data analysis.

Schematic diagram of the analgesic mechanism of vitamin D₃ in neuropathic pain. Vitamin D₃ protects GABAergic interneurons against ferroptosis through activation of VDR and repression of PKCα-NOX4 signaling-mediated mitochondrial dysfunction.

We developed a new taVNS method for safe, tolerable, and effective repetitive stimulation of awake mice. The administration of taVNS to awake mice for three consecutive weeks significantly improved memory but had no effect on anxiety-like behaviors.

Experimental hypothesis: CircAnks1b is upregulated by physical exercise in neurons of peri-infarct cortex. CircAnks1b competitively binds to miR-130b-5p, thereby mitigating miR-130b-5p-mediated suppression of Pak2 mRNA expression. Ensuing Pak2 expression increases IRE1a/XBP1 signaling pathway activity, which promotes protective ER stress in neurons and reduces apoptosis. High plasma circAnks1b expression also predicts superior neurological recovery in IS patients.