The cover image is based on the Commentary Prehospital stroke care in Africa: The reality and potential solutions by Rita Melifonwu et al., https://doi.org/10.1111/cns.14005.

Diagrams of representative non-invasive and invasive brain stimulation techniques. (A) represents the standard figure-eight transcranial magnetic stimulation (TMS) coil, which is connected to intensity and pulse regulator. (B) exhibits bipolar transcranial direct current stimulation (tDCS) electrodes and current regulator. (C) shows deep brain stimulation (DBS) microelectrodes inserted in brain and connected to a stimulator implanted elsewhere.

Metabolic changes of astrocytes in neurodegenerative diseases. In neurodegenerative diseases, the exchange of metabolites among astrocytes, neurons, and microglia has changed greatly, which aggravates the occurrence and development of neurodegenerative diseases. Astrocytes lose their homeostasis function. On the one hand, they are reactive to inflammatory factors of microglia. On the other hand, they fail to support the health of neurons. In addition, they also secrete many toxic factors that affect neurons.

Abnormal activation of TFEB leads to dysfunction of ALP pathway in neurodegenerative diseases. Growing evidence shows that overexpression of TFEB or TFEB-targeted small molecules promotes the degradation of abnormal aggregation proteins and significantly improves the abnormal behavioral characteristics of animal models. This review mainly summarize the regulatory mechanism of TFEB and its function in neurodegenerative diseases.

Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. Cortico-cortical and cortical-subcortical connectivity might be an essential aspect in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for older ADHD (mainly for adults with ADHD).

Neurofilaments assessed in cerebrospinal fluid before diagnosis of ALS at the neuromuscular reference center decreased the diagnostic delay by 3 months only when other covariates like disease progression rate and the presence of a genetic mutation were not considered.

Eight weeks of swimming training make Shank3 knockout pups improve autistic-like behaviors such as learning memory in rats, increase hippocampal volume, and increase dendritic spine complexity in hippocampal neurons.

miRNA-140-5p inhibitor ameliorated cognitive deficits induced by AßO. Further, miR-140-5p downregulation was associated with suppressing neuroinflammation and abnormal tau phosphorylation. This study exhibits a crucial role for miR-140-5p in the key events of oligomeric amyloid-beta induced neurotoxicity, which may serve as a potential therapeutic target for AD.

Ketamine holds promise as a neuroprotective agent through attenuating damage caused by the excitotoxic cascade. Though extensively studied in a stroke model, application to post-cardiac arrest brain injury has been overlooked. This scoping review summarizes the mechanism of ketamine neuroprotection as applicable to post-cardiac arrest brain injury, and existing evidence for the benefits of its use.

Using the noninvasive diffusion tensor image analysis along the perivascular space (DTI-ALPS) method, this study revealed compromised glymphatic circulation and its significant associations with age, age at disease onset and sleep disorders in Parkinson's disease and supported that glymphatic function may underpin the involvement of aging in the pathophysiology of Parkinson's disease.

In this study, we systematically explored the relationship between Alzheimer's disease (AD) and non-pathogenic variants of APP, PSEN1, and PSEN2 in a total of 3557 individuals in a Chinese population. The common variant association test revealed that PSEN2 rs11405 were nominally associated with AD. Gene-based association analysis indicated that non-pathogenic variants in APP gene may contribute to the etiology of AD. Our study indicated that non-pathogenic variants in PSEN2 and APP may be involved in AD pathogenesis in the Chinese population.

Selective brain hypothermia alleviated ischemia-induced neuronal loss and white matter injury, which was correlated with behavioral deficits. Furthermore, selective brain hypothermia suppressed the harmful immunological response by promoting the transformation of microglia/macrophages from the M1 to M2 phenotype. This polarization was negatively correlated with neuronal loss and white matter injury.

The role of gut bacteria in association with Parkinson's disease (PD) may involve the alterations of bacteria with the capacity to produce short-chain fatty acids (SCFAs) and an increase in putative pathobionts, which may work together to potentially impair the intestinal barrier and/or blood–brain barrier integrity, stimulating systemic and neural inflammation. SCFAs-producing bacteria may reduce or increase outside of an “optimal range”. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, the increased Bifidobacterium and Lactobacillus may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.

Six prediction models were constructed for POD using logistic regression, RF, AdaBoost, XGBoost, GBM, and stacking ensemble learning based on retrospective analysis of a large sample dataset. The logistic regression model had the same AUC(0.78) with the RF, and performed better than the machine learning models because of its better sensitivity, fewer variables, and easier interpretability.

Differentiation fate of NSCs is regulated by TAT-KIR. TAT-KIR inhibits the upregulation of p-AKT and p-STAT3 synchronously after IL-6 induction, giving rise to reduced differentiation of NSCs toward astrocytes. The level of p-JNK is elevated by IL-6 or/and TAT-KIR respectively via different ways, which probably coincided with the increased neuronal differentiation of NSCs. TAT-KIR could keep the level of p-ERK at a balance between normal and inflammatory states.

The occurrence of hypokalemia and its severity following traumatic brain injury can be predicted using first hospitalization day records and machine learning algorithms. The logistic regression algorithm showed the best predicting performance in five machine learning algorithms, verified by fivefold cross-validation and external validation to demonstrate the interpretability and generalizability of learned models.

Using dFNC analysis, we found that dyskinesia may be related to the dysfunctional inhibition of cognitive executive network on motor loops and excessive excitation of visual network and sensorimotor network, which provided evidence of the changes in brain dynamics associated with the occurrence of dyskinesia.

Intermittent hypoxia adaptation restores behavioral deficits induced by long-term hypoxia. (A) Pattern of intermittent hypoxia, 5 min 13% O₂ and 5 min 21% O₂ in total 10 cycles; (B) Intermittent hypoxia promoted increased flux in mice; (C) Intermittent hypoxia promoted the increase of SO₂% in mice; (D) Schematic representation of the experimental design. The four intermittent hypoxic mode phase adaptations include Mode①: 5 min 7% O₂ and 5 min 13% O₂, a total of 10 cycles. Mode②: 5 min 10% O₂ and 5 min 13% O₂, a total of 10 cycles. Mode③: 5 min 21% O₂ and 5 min 13% O₂, a total of 10 cycles. Mode④: 5 min 30% O₂ and 5 min 13% O₂, a total of 10 cycles. Behavioral tests were performed at 0, 7, and 14 d of hypoxia treatment. (E) The recordings of mice duration on the rotarod test. (F) The discrimination index of mice in novel object recognition. (G, H) The latency and the crossing numbers of mice were recorded in the Morris water maze test. (I, J): Comparison of the effects of four modes of intermittent hypoxia adaptation to alleviate cognitive impairment induced by long-term hypoxia. Data are expressed as the mean ± SEM, n = 10; *p < 0.05; **p < 0.01 versus the Con group. ^#p < 0.05 versus the H14d group.

The schematic diagram of neuroprotective and anti-ferroptotic effects of Netrin-1: Upregulation of NTN1 and activation of UNC5B receptor after TBI promote Nrf2 nuclear translocation and enhance GPX4 transcription. Exogenous Netrin-1 treatment alleviates ferroptosis and improves neurological deficits.

SASH1 expression increased significantly during NSCs differentiation into glial cells and spinal cord injury (SCI). SASH1 knockdown in primary astrocytes increased the release of BDNF and promoted axonal growth; SASH1 knockdown significantly reduced astrocytes activation and improved the recovery of function after SCI.

Campylobacterota was the most abundant microbiota enriched in chronic stress mice based on 16S rRNA gene sequencing. Campylobacterota-associated metabolites were significantly enriched mainly in the d-glutamate and d-glutamine metabolism through UHPLC-MS/MS-based metabolomics. Hyperbaric oxygen improves depression-like behaviors in chronic stress model mice by mainly regulating gut flora-associated metabolites.

Ginsenoside Rg1, a neuroprotective herb, could promote the repair of injury neurons and reverse motor dysfunction caused by spinal cord injury (SCI). In this study, ginsenoside Rg1 is proven to have positive effects on the directly transdifferentiation of astrocyte-to-neuron after SCI in vivo and vitro. The underlying mechanism of this process may proceed by blocking Notch/Stat3 signal pathway. The intervention of ginsenoside Rg1 could give a novel and optional select to the clinical applications.

Mutations in the KCNH1 cause a spectrum of epileptic disorders ranging from a benign form of genetic isolated epilepsy/febrile seizure to intractable form of epileptic encephalopathy. The genotypes and variant locations help explaining the phenotypic variation of patients with KCNH1 variant.

A machine learning model and a web predictor for delirium after surgery for degenerative spinal disease are successfully developed to demonstrate the extent of POD risk during the perioperative period, which could guide appropriate preventive measures for high-risk patients.

Consciousness is dependent on complex dynamics within the brain and that it may originate from the anterior cortex. The feathers of the source-level microstate may be generalizable markers for consciousness during the generation and recovery processes.

It is the first time that intravenous anesthetics have an effect on learning and memory function in invertebrates, and a new potential mechanism has been found.

The spatial transcriptome demonstrated that the expression level of CCL5 in the hippocampus of KA-induced seizure mice model was significantly increased. Under the treatment of maraviroc, the reduction of seizure behavior, neuronal degeneration, and glial cell activation were observed, and the survival rate of seizure mice was improved.

Cells responsive to valproic acid (VPA) showed decreased expression of Homer1b/c, reactive oxygen species production, and LDH release. On the contrary, overexpression of Homer1b/c interrupted VPA efficacy, resulting in higher reactive oxygen species production, calcium content, and LDH release.

Study design.

Phosphodiesterases and inflammation play a role in the pathophysiology of schizophrenia negative symptoms. Treatment with the PDE inhibitor pentoxifylline improve the expression of cAMP and decreases the expression of inflammatory cytokines including TNF-α and IL-6. Upregulation of cAMP/PKA signaling triggers the synthesis of dopamine at dopaminergic synapse, blocks the dopamine D2-receptor, and activates dopamine D1-receptor in striatonigral neurons. Pentoxifylline adjunctive therapy with risperidone for 8-weeks demonstrated a favorable efficacy and safety profile in improving the negative symptoms in patients with chronic schizophrenia.

Schematic illustrating the effect of Tat on MAMs in neurons. Tat affects the interaction between MAM tethering proteins IP3R and VDAC, Bap31 and Fis1, Bap31 and Tomm40, and PTPIP51 and VDAC. The affected MAM tethering leads to dysregulated calcium transfer between the ER and mitochondria and increased ROS. Tat also affects PTPIP51 phosphorylation and thus its localization to MAMs. Kinase inhibitors gefitinib, dasatinib, and Rp-cAMPs together can block PTPIP51 tyrosine phosphorylation even in the presence of Tat and can lead to PTPIP51 and VAPB interactions.

Claustrum neuronal activity is dramatically suppressed in propofol anaesthesia. Activation of claustral neurons resulted in an attenuated propofol sensitivity, shorter anaesthesia duration, and a wake shift of EEG. GABAa receptors in the claustrum also modulate anaesthesia sensitivity and cortical delta waves.

The proposed mechanism of sepsis-associated encephalopathy. HPC-PFC pathway plays an important role in cognitive dysfunction in sepsis-associated encephalopathy (SAE). Specifically, CaMKII/CREB/BDNF pathway in the glutamate receptor-mediated downstream signaling appears to be an important molecular mechanism linking the HPC-mPFC pathway with impairing spatial memory in SAE.

Digital therapeutics using sound stimulation has the potential to be used as a safe treatment method that can replace neuropharmacological treatment and electrical stimulation. Stimulation of the auditory nerve using neutral music and air conduction can induce the activation of the reticular activating system. Finally, It was confirmed that the stimulation has a value that can replace drugs by inducing changes in the nervous system similar to those induced by propofol for the sedative effect.

These findings may provide an underlying mechanism that white matter hyperintensities affects executive function and information processing speed via impairing the white matter integrity. It may be helpful in providing theoretical basis for rehabilitation strategies of cognitive function in patients with silent cerebrovascular diseases.

Workflow describing steps involved in the lectin microarray to understand the glycosignature in the mixed culture model.

Efflux of levofloxacin from the CNS involves MRPs, BCRP, and OATs. MRPs are the major drug transporter limiting levofloxacin distribution in brain and its inhibitors can effectively improve blood–brain and blood–cerebrospinal fluid barrier permeability of levofloxacin. In addition, CSF can be used as a surrogate to predict the brain ECF concentration of levofloxacin.

Neuronal damage of traumatic brain injury (TBI) rats commonly leads to severe neurological dysfunctions. Pathological results show that cortical neurons in TBI rats exhibit a wide range of degenerative changes, including atrophy, deformation, and disordered alignment, which can be improved by acupuncture. These results raise the question of the underlying molecular mechanism of acupuncture-induced morphological restoration of neurons in TBI rats.

This study suggested that GBE reduces the hippocampal inflammation by down-regulating lncRNA-COX2/NF-κB signaling in the SE mice, leading to the improvement of memory functions.