Adult Central Nervous System Research Articles

Regulation of neural stem cells by innervating neurons.

The adult central nervous system (CNS) hosts several niches, in which the neural stem and precursor cells (NPCs) reside. The subventricular zone (SVZ) lines the lateral brain ventricles and the subgranular zone (SGZ) is located in the dentate gyrus of the hippocampus. SVZ and SGZ NPCs replace neurons and glia in the homeostatic as well as diseased or injured states. Recently, NPCs have been found to express neurotransmitter receptors, respond to electrical stimulation and interact with neurons, suggesting that neuron-NPC communication is an emerging critical regulator of NPC biology. In this review, we discuss reports that demonstrate neuronal innervation and control of the neurogenic niches. We discuss the role of innervating neurons in regulating NPC fates, such as activation, proliferation, and differentiation. Our review focuses primarily on the innervation of the SVZ niche by the following neuronal types: glutamatergic, GABAergic projection and interneurons, cholinergic, dopaminergic, serotonergic, neuropeptidergic, nitrergic, and noradrenergic. We also discuss the origins of SVZ niche innervating neurons, such as striatum, cortex, basal ganglia, raphe nuclei, substantia nigra and ventral tegmental area, hypothalamus, and locus coeruleus. Our review highlights the various roles of innervating neurons in SVZ NPC fates in a spatiotemporal manner and emphasizes a need for future investigation into the impact of neuronal innervation on NPC gliogenesis.

Octadecaneuropeptide promotes the migration of astrocyte via ODN metabotropic receptor and calcium signaling pathway.

Migration is an essential characteristic of cells that occurs during many physiological and pathological processes. Astrocytes represent the most abundant cell type in the adult central nervous system (CNS), that play a crucial role in various functions such as guiding and supporting neuronal migration during development and maintaining brain homeostasis at adulthood. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). ODN is an endogenous ligand for both central-type benzodiazepine receptors and a metabotropic receptor. ODN promotes proliferation and prevents oxidative damage induced apoptosis on both neurons and astrocytes. However, little is known regarding the effect of ODN on cell migration. The purpose of the present study was to investigate the potential effect of ODN on astrocytes migration. Our results show that ODN stimulates astrocytes proliferation and migration at very low concentrations in wound healing assays, that was mimicked by the metabotropic ODN receptor agonist cyclo1-8 octapeptide (cyclo1-8OP, 10-14 M to 10-10 M). The effect of ODN on astrocyte migration was abrogated by the metabotropic receptor antagonist, cyclo1-8[DLeu5] OP. Moreover, we have shown that ODN activates the calcium signaling pathway and increases the mammalian target of rapamycin (mTOR) gene transcription, which are both known to promote astrocyte migration. Therefore, the present results suggest that ODN regulates astroglial cell migration through the calcium/mTOR signaling pathway and provide new insight regarding the role of ODN on brain remodling after injury.

Elimination of High-grade Gliomas Through Induced Cytolysis, Elucidated by Two Patient Cases.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant tumors in the central nervous system of adults. In practice, all patients with GBM experience relapse, and treatment options become limited following first-line therapy. We previously reported a new, successful treatment approach for a GBM patient, implemented in direct conjunction with surgical intervention. Here, we present an additional case demonstrating the success of this protocol, along with an overview of its underlying rationale and mechanisms. Following maximal safe tumor resection, our protocol involves the placement of two catheters in the tumor excision bed, connected to drug infusion pumps for continuous administration. The tumor's excision beds are irrigated for 90-120 hours with a slightly alkaline Tris-buffered solution containing L-2,4 diaminobutyric acid, an unnatural amino acid, and Prazosin, a proapoptotic drug widely used as an antihypertensive. Both patients demonstrated marked clinical improvement. Recent contrast-enhanced magnetic resonance imaging revealed no evidence of malignancy, with Case 1 remaining disease-free for seven years and Case 2 for two years of follow-up. This innovative approach not only enhances local drug delivery but also minimizes systemic side effects, addressing a critical challenge in GBM treatment. These cases highlight the potential of this protocol as an adjunct to standard therapies, offering a promising option for managing inoperable or recurrent GBM.

Glutathione peroxidase 4 overexpression induces anomalous subdiffusion and impairs glioblastoma cell growth

Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young’s modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young’s modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression.

Key epigenetic and signaling factors in the formation and maintenance of the blood-brain barrier.

The blood-brain barrier (BBB) controls the movement of molecules into and out of the central nervous system (CNS). Since a functional BBB forms by mouse embryonic day E15.5, we reasoned that gene cohorts expressed in CNS endothelial cells (EC) at E13.5 contribute to BBB formation. In contrast, adult gene signatures reflect BBB maintenance mechanisms. Supporting this hypothesis, transcriptomic analysis revealed distinct cohorts of EC genes involved in BBB formation and maintenance. Here, we demonstrate that epigenetic regulator's histone deacetylase 2 (HDAC2) and polycomb repressive complex 2 (PRC2) control EC gene expression for BBB development and prevent Wnt/β-catenin (Wnt) target genes from being expressed in adult CNS ECs. Low Wnt activity during development modifies BBB genes epigenetically for the formation of functional BBB. As a Class-I HDAC inhibitor induces adult CNS ECs to regain Wnt activity and BBB genetic signatures that support BBB formation, our results inform strategies to promote BBB repair.

Injury-induced KIF4A neural expression and its role in Schwann cell proliferation suggest a dual function for this kinesin in neural regeneration.

Contrary to the adult central nervous system, the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regeneration-associated genes, such as some kinesin family members. Kinesins contribute to nerve regeneration through the transport of specific cargo, such as proteins and membrane components, from the cell body towards the axon periphery. We show here that KIF4A, associated with neurodevelopmental disorders and previously believed to be only expressed during development, is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells. KIF4A is detected both in the cell bodies and regrowing axons of injured neurons, consistent with its function as an axonal transporter of cargoes such as β1-integrin and L1CAM. Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps, particularly at a time when they are reprogrammed into an essential proliferative repair phenotype. Moreover, Kif4a mRNA levels were approximately ~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones. A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown, as this significantly reduced Schwann cell proliferation in vitro. Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury. The timing of KIF4A up-regulation, its location during regeneration, and its proliferative role, all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.

Glioblastoma and its interaction with neurogenesis

Glioblastoma (GBM) is the most frequent and aggressive malignant primary tumor of the central nervous system in adults, with an incidence of 3.23 per 100,000 people. Despite the existence of various therapeutic approaches, the absence of a cure and the unfavorable prognosis persist for this neoplasm, with a median survival of approximately 8-15 months and a 5-year survival rate of 6.9%. In this review, we address the epidemiology, histopathology, molecular characteristics, and treatment of GBM. We highlight the relationship of GBM with the microenvironment in the lateral ventricle wall and the cerebrospinal fluid. The location of GBM in this region results in more aggressive tumors and shorter life expectancy for patients. Understanding the malignancy mechanisms that hinder remission, treatment, and positive prognosis opens the possibility of improving diagnostic and therapeutic interventions against GBM.

GelMA microneedle-loaded bio-derived nanovaccine shows therapeutic potential for gliomas

ABSTRACT Glioma is the most common primary malignant tumor of the central nervous system in adults. Although immunotherapy, especially tumor vaccines, has made some progress in the treatment of gliomas compared with surgery and radiotherapy. However, the lack of specific or relevant tumor antigens severely limits the further development of tumor vaccines. Here, we report a bio-derived vaccine (TMV@CpG) derived from glioma cell membrane vesicles and carrying TLR9 agonist CpG as adjuvant, which was loaded onto the GelMA microneedle to obtain the microneedle vaccine (MN-TMV@CpG). Microneedle vaccine fully utilize the innate immune cells rich in the skin, inducing stronger cellular immune responses. In subcutaneous tumor models, MN-TMV@CpG reversed the immune-suppressing microenvironment of tumor, and effectively inhibited tumor progression. In an intracranial tumor model, MN-TMV@CpG significantly prolonged the survival duration and induced stronger immune memory responses in tumor bearing mice when combined with anti-PD1 mAb. These results suggest that bio-derived nanovaccines can be used as a potential antitumor immunotherapy strategy.

Cephalic ganglia transcriptomics of the American cockroach Periplaneta americana (Blattodea: Blattidae).

The American cockroach Periplaneta americana (L.) (Blattodea, Blattidae) has been a model organism for biochemical and physiological study for almost a century, however, its use does not benefit from the genetic tools found in key model species such as Drosophila melanogaster. To facilitate the use of the cockroach as a model system in neuroscience and to serve as a foundation for functional and translational experimentation, a transcriptome of the cephalic ganglia was assembled and annotated, and differential expression profiles between these ganglia were assessed. The transcriptome assembly yielded >400 k transcripts, with >40 k putative coding sequences. Gene ontology and protein domain searches indicate the cerebral and gnathal ganglia (GNG) have distinct genetic expression profiles. The developmental Toll signaling pathway appears to be active in the adult central nervous system (CNS), which may suggest a separate role for this pathway besides innate immune activation or embryonic development. The catabolic glycolytic and citric acid cycle enzymes are well represented in both ganglia, but key enzymes are more highly expressed in the GNG. Both ganglia express gluconeogenic and trehaloneogenic enzymes, suggesting a larger role of the CNS in regulating hemolymph sugar homeostasis than previously appreciated. The annotation and quantification of the cephalic ganglia transcriptome reveal both canonical and novel pathways in signaling and metabolism in an adult insect and lay a foundation for future functional and genetic analysis.

Impact of Age and Gender on Survival of Glioblastoma Multiforme Patients: A Multicenter Retrospective Study.

Glioblastoma multiforme (GBM) poses a significant health challenge as the most common primary malignancy of the adult central nervous system. Gender- and age-related differences in GBM influence prognosis and treatment complexities. This multicenter retrospective study explores gender and age disparities in GBM patients, investigating their impact on occurrence and survival outcomes. This multicenter retrospective study involved GBM patients treated in Guilan Province, Iran. Patients' data, including age, gender, tumor location, and histopathological diagnosis date, was collected from medical records. In a cohort of 164 GBM patients, the average age was 54.34 ± 14.16 years, with a higher prevalence among men (59.8%) and patients aged ≤ 60 years (64.6%). The tumor sites exhibited overlapping features in 68% of cases, with the frontal and temporal lobes being the most common specific locations. The mean survival was 12.88 ± 14.14 months, one-year survival of 45%, with women showing significantly higher one-year survival (60% vs. 40%) and longer mean survival (16.14 ± 17.35 vs. 10.75 ± 11.15 months). Furthermore, Patients ≤ 60 years had significantly higher one-year survival (75% vs. 35%). In subgroup analysis, women had significantly higher survival rates in patients ≤ 60 years. However, among patients over 60, women exhibited a more pronounced decline in survival rates, with no statistically significant difference between men and women in this age group. This study highlights that both age and gender significantly affect GBM survival outcomes. Younger patients, particularly women, exhibited better survival rates, while older patients, especially women, showed poorer outcomes. These findings suggest the need to stratify treatment approaches by both age and gender to optimize care and improve survival in GBM patients. Further research is recommended to explore these associations.

Transcriptional profiles of murine oligodendrocyte precursor cells across the lifespan.

Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system (CNS) that are responsible for generating myelinating oligodendrocytes during development. By also generating new oligodendrocytes in the adult CNS, OPCs allow formation of new myelin sheaths in response to environmental and behavioral changes and play a crucial role in regenerating myelin following demyelination (remyelination). However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination, and adaptive myelination during learning. To determine how aging influences OPCs, we generated a novel transgenic mouse line that expresses membrane-anchored EGFP under the endogenous promoter/enhancer of Matrilin-4 (Matn4-mEGFP) and performed high-throughput single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescence to proliferation and differentiation across the lifespan. Comparative analysis of OPCs isolated from mice aged 30 to 720 days, revealed that aging induces distinct inflammatory transcriptomic changes in OPCs in different states, including enhanced activation of HIF-1α and Wnt pathways. Inhibition of these pathways in acutely isolated OPCs from aged animals restored their ability to differentiate, suggesting that this enhanced signaling may contribute to the decreased regenerative potential of OPCs with aging. This Matn4-mEGFP mouse line and single-cell mRNA datasets of cortical OPCs across ages help to define the molecular changes guiding their behavior in various physiological and pathological contexts.

Tissue-Specific Immune Transcriptional Signatures in the Bordering Tissues of the Mouse Retina and Brain.

Bordering the central nervous system (CNS) parenchyma are the choroid (underlying the retina) and the leptomeninges (the inner layers of the meninges enveloping the brain). Although near the neural parenchyma, the choroid and leptomeninges are external to the immune privileged environment of the retina and brain and thus are distinct immune compartments. This study aimed to characterize the transcriptomic signatures of immune cells within the choroid and leptomeninges bordering the healthy adult mouse CNS. Eyes and brains were obtained from 7-week-old C57Bl/6J mice. Choroid and leptomeninges were processed for isolation of CD45+ immune cells and single cell RNA-sequencing. Additionally, single cell RNA-sequencing was performed on immune cells isolated from choroid obtained from human donor eye tissue. Immunostaining and confocal microscopy of wholemount tissue were used to validate selected immune cell populations in situ. A total of 3606 cells were sequenced from mouse tissues, including 2125 CD45+ cells from choroid and 1481 CD45+ cells from leptomeninges. Clustering and differential gene expression analysis revealed heterogeneous subtypes of monocytes/macrophages, dendritic cells, T cells, and B cells. Whereas some clusters were common to both choroid and leptomeninges, others exhibited tissue-specific gene expression profiles and potential functional specializations. Analysis of 6501 CD45+ cells sequenced from human choroid identified similar immune cell populations to mouse choroid. This study provides a detailed characterization of the molecular signatures of immune cells within the vascular connective tissues bordering the healthy retina and brain, and their potential roles in immune protection.

Neurotrophic extracellular matrix proteins promote neuronal and iPSC astrocyte progenitor cell- and nano-scale process extension for neural repair applications.

The extracellular matrix plays a critical role in modulating cell behaviour in the developing and adult central nervous system influencing neural cell morphology, function and growth. Neurons and astrocytes, play vital roles in neural signalling and support respectively and respond to cues from the surrounding matrix environment. However, a better understanding of the impact of specific individual extracellular matrix proteins on both neurons and astrocytes is critical for advancing the development of matrix-based scaffolds for neural repair applications. This study aimed to provide an in-depth analysis of how different commonly used extracellular matrix proteins- laminin-1, Fn, collagen IV, and collagen I-affect the morphology and growth of trophic induced pluripotent stem cell (iPSC)-derived astrocyte progenitors and mouse motor neuron-like cells. Following a 7-day culture period, morphological assessments revealed that laminin-1, fibronectin, and collagen-IV, but not collagen I, promoted increased process extension and a stellate morphology in astrocytes, with collagen-IV yielding the greatest increases. Subsequent analysis of neurons grown on the different extracellular matrix proteins revealed a similar pattern with laminin-1, fibronectin, and collagen-IV supporting robust neurite outgrowth. fibronectin promoted the greatest increase in neurite extension, while collagen-I did not enhance neurite growth compared to poly-L-lysine controls. Super-resolution microscopy highlighted extracellular matrix-specific nanoscale changes in cytoskeletal organization, with distinct patterns of actin filament distribution where the three basement membrane-associated proteins (laminin-1, fibronectin, and collagen-IV) promoted the extension of fine cellular processes. Overall, this study demonstrates the potent effect of laminin-1, fibronectin and collagen-IV to promote both iPSC-derived astrocyte progenitor and neuronal growth, yielding detailed insights into the effect of extracellular matrix proteins on neural cell morphology at both the whole cell and nanoscale levels. The ability of laminin-1, collagen-IV and fibronectin to elicit strong growth-promoting effects highlight their suitability as optimal extracellular matrix proteins to incorporate into neurotrophic biomaterial scaffolds for the delivery of cell cargoes for neural repair.

Synaptotagmin 4 Supports Spontaneous Axon Sprouting after Spinal Cord Injury.

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function.

FBXW7 regulates MYRF levels to control myelin capacity and homeostasis in the adult CNS.

Myelin, along with the oligodendrocytes (OLs) that produce it, is essential for proper central nervous system (CNS) function in vertebrates. Although the accurate targeting of myelin to axons and its maintenance are critical for CNS performance, the molecular pathways that regulate these processes remain poorly understood. Through a combination of zebrafish genetics, mouse models, and primary OL cultures, we found FBXW7, a recognition subunit of an E3 ubiquitin ligase complex, is a regulator of adult myelination in the CNS. Loss of Fbxw7 in myelinating OLs resulted in increased myelin sheath lengths with no change in myelin thickness. As the animals aged, they developed progressive abnormalities including myelin outfolds, disrupted paranodal organization, and ectopic ensheathment of neuronal cell bodies with myelin. Through biochemical studies we found that FBXW7 directly binds and degrades the N-terminal of Myelin Regulatory Factor (N-MYRF), to control the balance between oligodendrocyte myelin growth and homeostasis.

Heterogeneity in oligodendrocyte precursor cell proliferation is dynamic and driven by passive bioelectrical properties

Oligodendrocyte precursor cells (OPCs) generate myelinating oligodendrocytes and are the main proliferative cells in the adult central nervous system. OPCs are a heterogeneous population, with proliferation and differentiation capacity varying with brain region and age. We demonstrate that during early postnatal maturation, cortical, but not callosal, OPCs begin to show altered passive bioelectrical properties, particularly increased inward potassium (K+) conductance, which correlates with G1 cell cycle stage and affects their proliferation potential. Neuronal activity-evoked transient K+ currents in OPCs with high inward K+ conductance potentially release OPCs from cell cycle arrest. Eventually, OPCs in all regions acquire high inward K+ conductance, the magnitude of which may underlie differences in OPC proliferation between regions, with cells being pushed into a dormant state as they acquire high inward K+ conductance and released from dormancy by synchronous neuronal activity. Age-related accumulation of OPCs with high inward K+ conductance might contribute to differentiation failure.

Intraperitoneal Injection of the Porphyromonas gingivalis Outer Membrane Vesicle (OMV) Stimulated Expressions of Neuroinflammatory Markers and Histopathological Changes in the Brains of Adult Zebrafish.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, which leads to neuroinflammation. The bacteria destroy periodontal tissue through virulence factors, which are retained in the bacteria's outer membrane vesicles (OMV). This study aimed to determine the real-time effect of an intraperitoneal injection of P. gingivalis OMV on the production and expression of inflammatory markers and histopathological changes in adult zebrafishes' central nervous systems (CNS). Following the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMVs, and the control group were injected with normal saline at seven different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA, and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 min, while IL-1β and IL-6 were expressed at subsequent 12 h and 24 h time points, respectively. Histopathological changes such as blood coagulation, astrocytosis, edema, spongiosis, and necrosis were observed between the 6hour and 24 h time points. The two apoptotic enzymes, caspases 3 and 9, were not expressed at any point. In summary, the OMV-induced neuroinflammatory responses and histopathological changes in adult zebrafish were time-point dependent. This study will enrich our understanding of the mechanism of P. gingivalis OMVs in neuroinflammation in a zebrafish model, most especially the timing of the expression of inflammatory mediators in relation to observable changes in brain tissues.

Role of Microglia in Central Nervous System Development and Plasticity.

The nervous system comprises a remarkably diverse and complex network of cell types, which must communicate with one another with speed, reliability, and precision. Thus, the developmental patterning and maintenance of these cell populations and their connections with one another pose a rather formidable task. Emerging data implicate microglia, the resident myeloid-derived cells of the central nervous system (CNS), in spatial patterning and synaptic wiring throughout the healthy, developing, and adult CNS. Importantly, new tools to specifically manipulate microglia function have revealed that these cellular functions translate, on a systems level, to effects on overall behavior. In this review, we give a historical perspective of work to identify microglia function in the healthy CNS, and highlight exciting new discoveries about their contributions to CNS development, maintenance, and plasticity.

Characteristics and Survival of Patients with WHO Grade 4 Diffuse Glioma in Dharmais National Referral Cancer Hospital

Background: The WHO grade 4 diffuse glioma are extremely aggressive and account for over 60% of adult Central Nervous System (CNS) tumors. The diagnosis and management pose significant challenges due to the need for comprehensive evaluation and holistic treatment approaches. This study aims to determine the clinical characteristics of WHO grade 4 diffuse glioma in Indonesia and the overall survival as a secondary goal. Methods: This is a retrospective cohort study of all WHO grade 4 glioma patients from 2017 to 2022 at Dharmais National Cancer Hospital, Jakarta, Indonesia. Demographic characteristics were presented descriptively. Kaplan-Meier plot was used to evaluate the median survival. Results: Twenty-eight patients were eligible for this study. The median age group is 45 years old, with equal male and female prevalence. Headache was the most prevalent primary symptom. The therapy following surgery was radiotherapy (RT) with chemosensitizer (82.1%) and RT alone (14.3%) with both followed by adjuvant chemotherapy. There was one patient (3.6%) underwent palliative therapy. The median survival of all patients was 10 months, whereas 10 months in RT with the chemo-sensitizer group and 1 month in RT only group. There was no statistically significant difference between RT with and without chemotherapy sensitizer in terms of survival rates. Conclusions: Our study reports a younger median age of WHO Grade 4 diffuse glioma. Male subjects were equivalent to females. Median OS was 10 months and were longer in RT with the chemosensitizer group. Further multicentered and at the genetic level investigation was needed, to achieve optimal outcomes.

Machine learning predicts cuproptosis-related lncRNAs and survival in glioma patients.

Gliomas are the most common tumor in the central nervous system in adults, with glioblastoma (GBM) representing the most malignant form, while low-grade glioma (LGG) is a less severe. The prognosis for glioma remains poor even after various treatments, such as chemotherapy and immunotherapy. Cuproptosis is a newly defined form of programmed cell death, distinct from ferroptosis and apoptosis, primarily caused by the accumulation of the copper within cells. In this study, we compared the difference between the expression of cuproptosis-related genes in GBM and LGG, respectively, and conducted further analysis on the enrichment pathways of the exclusive expressed cuproptosis-related mRNAs in GBM and LGG. We established two prediction models for survival status using xgboost and random forest algorithms and applied the ROSE algorithm to balance the dataset to improve model performance.