Alzheimer’s disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using ¹⁸F-labed fluorodeoxyglucose (¹⁸F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

Parkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

The Notch signaling pathway, an evolutionarily conserved mechanism governing cell-cell communication, plays a pivotal and multifaceted role in shaping the

Tryptophan metabolism plays a critical role in glioblastoma (GBM), however, the regulatory functions of kynurenic acid (KYNA) in this context remain poorly understood. Using an in‐house clinical cohort, targeted metabolomic analysis revealed significantly downregulated KYNA levels in GBM tissues compared to non‐tumor brain tissues. Further investigation demonstrated that KYNA administration markedly reduced tumor burden in an orthotopic GBM mouse model. Through integrated cytometry by time‐of‐fight (CyTOF), single‐cell RNA sequencing (scRNA‐seq), proteome, and flow cytometry analyses, this study delineated the alterative tumor immune landscape following KYNA treatment. Specifically, KYNA remodeled the immunosuppressive myeloid compartment within the GBM microenvironment. Additionally, KYNA reversed T cell exhaustion signatures, enhanced cytotoxic function, thereby augmented anti‐tumor T cell responses. Notably, the anti‐tumor effects of KYNA are abrogated in T cell‐deficient mouse models (nude and Rag2‐/‐), confirming its dependence on adaptive immunity. In summary, this study highlights the therapeutic potential of KYNA in GBM and provides a comprehensive, multi‐omics‐based understanding of its immunomodulatory mechanisms.

Ischemic stroke triggers a cascade of mitochondrial dysfunction, oxidative stress, neuroinflammation, and pyroptosis, ultimately leading to neuronal injury and neurological deficits. Therapeutic efficacy is often limited by inadequate blood–brain barrier penetration and off-target effects. To address these challenges, we designed 3R@Lipo/Gink, a biocompatible liposomal formulation modified with an ROS-responsive TK polymer and two functional peptides—RVG29 for enhanced brain delivery and MG1 for microglia enrichment—to enable precise transport of ginkgetin, which has been demonstrated to exert neuroprotective effects through multiple potential mechanisms, to ischemic lesions. In a middle cerebral artery occlusion/reperfusion model, 3R@Lipo/Gink markedly reduced infarct size, alleviated neuronal injury, and improved motor performance. Single-cell RNA sequencing and in vitro co-culture experiments identified microglia and neurons as the primary responsive cell types. Mechanistic studies showed that 3R@Lipo/Gink suppressed HIF-1α expression, thereby downregulating c-Myc–mediated microglial proliferation and attenuating NLRP3-dependent pyroptosis. These protective effects were reversed by FG-4592, a prolyl hydroxylase inhibitor that stabilizes HIF-1α, supporting the involvement of the HIF-1α pathway. Through mitigating microglial overactivation and interrupting the inflammatory-pyroptotic loop, 3R@Lipo/Gink ultimately remodels the microglia-mediated inflammatory microenvironment around neurons and improves functional recovery. These findings highlight 3R@Lipo/Gink as a promising targeted nanotherapeutic strategy for ischemic stroke and other nervous system diseases.

Multiple arachnoid cysts are very rare within the central nervous system. The cysts will sometimes increase in size with age, lead to the mass effect or cerebrospinal fluid (CSF) flow obstruction, and cause some symptoms, which requires the surgery intervention. A 35-year-old female was admitted to our hospital with some symptoms related to hydrocephalus for 1 month. Brain magnetic resonance imaging (MRI) revealed well-marginated cystic lesions with CSF signal intensity in the ventricular and cisternal systems, bilateral temporal lobes, and left occipital lobe. Cine phase-contrast MRI showed the aqueduct of sylvius was blocked by the cyst in the quadrigeminal cistern. We employed endoscopic ventriculocystostomy and septostomy to create the communication of the cyst with ventricular and cistern system. As a result, the patient’s symptoms were relieved. Endoscopic management can be an effective way for treating intracranial multiple arachnoid cysts, which is the first report of this kind. We hope that this report could help improve the management of intracranial arachnoid cysts with the neuroendoscopic technology.