Glial Tissue Research Articles

SURG-10. DEVELOPMENT OF 2 COMPLEMENTARY INNOVATIVE APPROACHES FOR REAL-TIME, LABEL-FREE INTRAOPERATIVE TUMOR DETECTION TO ENHANCE EXTENT OF RESECTION OF LOW GRADE GLIOMAS

Abstract Brain tumor surgery aims to maximize tumor resection while avoiding neurological deficits. Accurate characterization of tissue and delineation of resection margins are essential to achieve optimal surgical outcome. Hyperspectral imaging (HSI) and Real-time Rapid Evaporative Ionization Mass Spectrometry ( REIMS) are both novel technological adjuncts able to accurately detect intraoperatively zones of low grade glioma without substantially altering the surgical work flow. For HSI, we successfully demonstrate how an HSI system can interface with a clinically approved surgical microscope making use of the microscope’s available light sources and optical ports. We integrated the HSI system into the clinical workflow during brain surgery, specifically for resections of low-grade gliomas (LGG). During the study the acquired dataset was used to train an AI algorithm to detect LGG, providing 81% accuracy on unseen data. Real-time Rapid Evaporative Ionization Mass Spectrometry (REIMS) enables in-situ tissue characterization based on the mass spectrometric analysis of electrosurgical vapors generated during dissection. We demonstrate the use of REIMS for the molecular characterization of brain tumor tissue, thereby providing quasi real-time assessment of tumor type. A classification model containing 31 sampling points in normal brain tissue and 93 in glial tumor tissue provided 89.3% sensitivity and 91.1% specificity. Both techniques, HSI and REIMS display a high intraoperative diagnostic accuracy in terms of glioma tissue detection and are complementary, real-time and label-free methods which we developed and tested up to the stage of high Technology Readiness levels (TRL) of 7 and 5 respectively.

Shinbaro2 enhances axonal extension beyond the glial scar for functional recovery in rats with contusive spinal cord injury

Spinal cord injury (SCI) is a devastating event that often results in the inflammatory condition of glial scar tissue formation, impeding neural regeneration and recovery. Reducing the inflammatory response and inhibiting glial formation are promising strategies for improving SCI outcomes. Here, we introduce a new role for Shinbaro2 (Sh2), known for its anti-inflammatory and pain-reducing effects, in ameliorating glial scars formed in the damaged spinal cord and promoting axon growth after SCI. Sh2 was applied at various concentrations to cultivate primary spinal cord neurons. Concentrations of 1 and 2 mg/mL effectively enhanced cell viability and axonal outgrowth in spinal cord neurons subjected to hydrogen peroxide or laceration injury. Sh2 helped reduce neuroinflammation by increasing anti-inflammatory M2 macrophages (arginase 1) and decreasing inflammatory cells, ultimately reducing lesion size. In scar formation, Sh2 inhibited the expression of β-catenin and nestin in reactive astrocytes in the injured spinal cord. Moreover, Sh2 suppressed the expression of chondroitin sulfate proteoglycans and SOX9, which are involved in scar formation. Furthermore, Sh2 promoted the sprouting of serotonergic axons and the growth of neurofibrillary tangles, enhancing motor function recovery in SCI. These findings highlight the potential of Sh2 as an SCI therapeutic intervention, offering hope for neural and functional restoration in individuals with this debilitating condition.

Endoscopic extended transforaminal approach (medial subchoroid) as an alternative to the classical transchoroidal approach: Technical note

The extended transforaminal endoscopic approaches allows visualization and manipulation of the middle and posterior third of the III ventricle. In selected cases where the venous anatomy is favorable, the medial subchoroidal approach can be performed as an alternative to the classic transchoroidal approach (via trans-taenia fornicis) with increased protection over the fornix and without the need to sacrifice the septal vein.We present a 14-year-old male with history of Neurofibromatosis type 1 referred for two weeks of clinical evolution with headache, dizziness, gait instability and appearance of a right VI nerve palsy. Magnetic resonance imaging showed obstructive tri-ventricular hydrocephalus due to stenosis of the aqueduct of Sylvius with suspicion of an underlying tumor. An endoscopic surgical procedure was performed through a single approach with III cisternostomy and resection of the tissue that produced the stenosis. The anatomopathological diagnosis showed reactive glial tissue with no signs of malignancy. In conclusion, the medial subchoroidal approach is a plausible alternative in the endoscopic approach to the III ventricle structures in a safe and comfortable manner.

Use of patient-specific 3D printed models in pre-operative counseling for pediatric skull base surgery.

Pediatric cranial base pathology is anatomically complex and surgical treatment is oftentimes difficult to conceptualize for patients and their families. Three-dimensional (3D) models of the sinuses and cranial base have the potential to enhance patient understanding in numerous domains. Our objective is to assess the use of 3D models in pre-operative parental and patient counseling prior to endoscopic endonasal skull base surgery in the pediatric population. A survey was designed to assess parent and patient-perceived utility of 3D-printed models in surgical counseling prior to pediatric skull base surgery. A total of 10 patients were included. The median age was 9 years (range=5 months-15 years). Pathology included juvenile nasopharyngeal angiofibroma (JNA) (N=4), fibrous dysplasia of the maxilla and sphenoid (N=1), juvenile ossifying fibroma (N=1), nasal dermoid (N=2, one with intracranial extension), encephalocele (N=1), and parapharyngeal ectopic glial tissue (N=1). Nearly all parents agreed or strongly agreed that 3D printed models were helpful in explaining the patient's skull base pathology (N=10), surgical plan (N=10), and possible complications (N=9). All parents strongly agreed that 3D models should be used routinely in pre-operative counseling for endoscopic endonasal surgery. According to a majority of parents, patients older than 4 years old found the models helpful in understanding their pathology (75%) and surgery (88%). By allowing direct three-dimensional visualization of the target pathology, 3D models serve as a useful adjunct in enhancing patient comprehension of the pathologic entity, planned surgery, and potential complications prior to pediatric endoscopic endonasal skull base surgery.

Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series

BackgroundDysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures. Proper surgical resection achieves long term seizure control. We describe the clinicopathological features of dysembryoplastic neuroepithelial tumor cases reported in our practice and review the published literature.MethodsAll cases of Pakistani ethnicity were diagnosed between 2015 and 2021 were included. Slides were reviewed and clinicopathological features were recorded. Follow-up was obtained. Extensive literature review was conducted.ResultsFourteen cases were reported. There were 12 males and 2 females. Age range was 9–45 years (mean 19 years). Majority were located in the temporal and frontal lobes. Duration of seizures prior to resection ranged from 2 months to 9 years with mean and median duration of 3.2 and 3 years, respectively. Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons. Simple and complex forms comprised seven cases each. No significant nuclear atypia, mitotic activity, or necrosis was seen. Ki-67 proliferative index was very low. Cortical dysplasia was noted in adjacent glial tissue in four cases. Follow-up ranged from 20 to 94 months. Seizures continued following resection in all but one case but were reduced in frequency and intensity. In one case, seizures stopped completely following surgery.ConclusionClinicopathological features were similar to those in published literature. However, a marked male predominance was noted in our series. Seizures continued following resection in all but one case but were reduced in frequency and intensity. This series will help raise awareness among clinicians and pathologists in our part of the world about this seizure-associated tumor of children and young adults.

Micromotion Derived Fluid Shear Stress Mediates Peri-Electrode Gliosis through Mechanosensitive Ion Channels.

The development of bioelectronic neural implant technologies has advanced significantly over the past 5 years, particularlyin brain-machine interfaces and electronic medicine. However, neuroelectrode-based therapies require invasive neurosurgery and can subject neural tissues to micromotion-induced mechanical shear, leading to chronic inflammation, the formation of a peri-electrode void and the deposition of reactive glial scar tissue. These structures act as physical barriers, hindering electrical signal propagation and reducing neural implant functionality. Although well documented, the mechanisms behind the initiation and progression of these processes are poorly understood. Herein, in silico analysis of micromotion-induced peri-electrode void progression and gliosis is described. Subsequently, ventral mesencephalic cells exposed to milliscale fluid shear stress in vitro exhibited increased expression of gliosis-associated proteins and overexpression of mechanosensitive ion channels PIEZO1 (piezo-type mechanosensitive ion channel component 1) and TRPA1 (transient receptor potential ankyrin 1), effects further confirmed in vivo in a rat model of peri-electrode gliosis. Furthermore, in vitro analysis indicates that chemical inhibition/activation of PIEZO1 affects fluid shear stress mediated astrocyte reactivity in a mitochondrial-dependent manner. Together, the results suggest that mechanosensitive ion channels play a major role in the development of a peri-electrode void and micromotion-induced glial scarring at the peri-electrode region.

Un lésion cérébrale déroutante

A 31-year-old man, with no past medical history, presented with headaches, sudden loss of vision, right exophtalmia, bilateral papilledema, and fever. Brain imaging noted a right basi-temporal lesion. Excision of the lesion was performed. The histological examination noted a glial tissue with acute inflammatory changes and multinucleated giant cells. Within this infiltrate there were septate and branched hyphae consistent with aspergillosis. These filaments were stained with PAS. The patient died post-operatively.

CDH1 hypermethylation: a potential molecular pathway for invasiveness in glioblastoma.

Glioblastoma is the most aggressive central nervous system primary tumor. Prognosis is poor, mainly due to the malignant characteristics of the tumor, such as high cell proliferation and invasiveness. CDH1 hypermethylation is linked to the invasive potential in various cancer types, but its importance is still unknown in glioblastoma. In this context, the methylation status of CDH1 was analyzed using MSP-PCR (Methylation-specific Polymerase Chain Reaction) in glioblastoma (n = 34) and normal glial tissue samples (n = 11). CDH1 hypermethylation was found in 39.4% (13/34) of the tumor samples and none of the normal glial tissue, suggesting a relation between CDH1 hypermethylation and glioblastoma ( P = 0.0195). Finally, this study showed unprecedented information that could contribute to clarifying the molecular pathways involved in the invasiveness and aggressiveness of this type of cancer.

Distinguishing Glial Tissue from Optic Disc in Bergmeister's Papilla Using OCT Angiography

A 55-year-old asymptomatic woman was found to have bilateral abnormalities of the optic nerve during an ophthalmic examination. Ocular examination revealed visual acuity of 20/20 in both eyes with normal anterior segment. Fundus examination showed grayish-white glial tissue covering the optic nerve (A) as confirmed by infrared image (B) from OCT. Cross-sectional OCT image (C) exhibited hyperreflective membrane overlying the optic disc, and adhesions to adjacent optic papilla structure (white arrow). The corresponding OCT angiography B-scan with flow overlay (D) showed hyperreflective tissue without any flow signal, contrasting with the optic disc's normal blood flow signal (Magnified version of Figure A-D is available online at www.aaojournal.org).

RARE FOREGUT CYST IN ORAL CAVITY

Foregut cysts are rare congenital choristomas arising from abnormal development of the foregut. Choristomas may comprise several different tissue types, including salivary glands (within the jawbone or gingival tissues), cartilaginous or bony lesions (mostly on the tongue), glial tissue (most common in the nasosinusal tract), or thyroid tissue. The aim of this report is to describe the unusual case of a neonate (2 months old) with a large congenital sublingual cystic lesion preventing breastfeeding, who was initially treated as a sublingual ranula using cryosurgery without success. An incisional biopsy was performed, which diagnosed a foregut cyst. The patient was referred to the Head and Neck Surgery team for enucleation, which resolved the lesion. The patient is under follow-up with no evidence of recurrence in six months. Foregut cysts are rare congenital choristomas arising from abnormal development of the foregut. Choristomas may comprise several different tissue types, including salivary glands (within the jawbone or gingival tissues), cartilaginous or bony lesions (mostly on the tongue), glial tissue (most common in the nasosinusal tract), or thyroid tissue. The aim of this report is to describe the unusual case of a neonate (2 months old) with a large congenital sublingual cystic lesion preventing breastfeeding, who was initially treated as a sublingual ranula using cryosurgery without success. An incisional biopsy was performed, which diagnosed a foregut cyst. The patient was referred to the Head and Neck Surgery team for enucleation, which resolved the lesion. The patient is under follow-up with no evidence of recurrence in six months.

Peritoneal and Nodal Gliomatosis Mimicking Metastasis on FDG PET/CT in a Patient With Ovarian Immature Teratoma.

Peritoneal and nodal gliomatosis is a rare disease condition characterized by implants of mature glial tissue on the peritoneum and lymph nodes. It is typically associated with teratoma and has no adverse effect on prognosis. We present a case of 22-year-old woman who underwent FDG PET/CT for the staging of ovarian immature teratoma. PET/CT revealed mildly increased FDG uptake in the peritoneal cavity and increased FDG uptake in the internal mammary and cardiophrenic angle lymph nodes, which were histopathologically diagnosed as peritoneal and nodal gliomatosis. This case suggests that PET/CT findings of peritoneal and nodal gliomatosis could mimic metastasis.

Hemihydranencephaly of Premature Infant - Case Report

Abstract Hydranencephaly represents a rare anomaly of the central nervous system and is characterized by the parenchymal absence which is replaced with a membranous sac filled with cerebrospinal liquid, glial tissue and ependyma. When it is manifested as hemihydranencephaly, the patient’s prognosis is better. We presented a case of a premature infant with hemihydranencephaly in twin pregnancy that had a fatal outcome. A premature infant in a controlled pregnancy was delivered at 31 weeks of gestational age. The mother of the newborn was hospitalized in the Clinic for Infective Diseases since she had tested positive for SARS-Covid- 19. Following an urgent Caesarean section, the newborn was tested for Covid 19 using the rapid antigen and PCR test and the results were negative. In the delivery room, the tactile stimulation, aspiration, positive pressure ventilation of the infant were applied, after which it was intubated. After the intubation, a manual heart massage was performed, after which the cardiac activity and agonal breathing movements were detected.” Three hours later, cardiorespiratory arrest happened, following unsuccessful resuscitation. The other twin was born with no anomalies, but showed signs of respiratory distress syndrome. Autopsy revealed that there was a thin-walled cavity filled with clear, yellowish liquid in the right hemisphere. Documenting cases of newborns with hydranencephaly is of a great importance for counseling parents regarding length of survival, successful management of pregnancy, and performance of prenatal diagnostic procedures.

Inhibited astrocytic differentiation in neural stem cell-laden 3D bioprinted conductive composite hydrogel scaffolds for repair of spinal cord injury

The emergence of three-dimensional (3D) bioprinting technology has attracted ever-increasing attention in engineered tissue fabrication for stem cell-based tissue repair. However, the in vivo performance of transplanted stem cells in the tissue engineering scaffolds is still a major concern for regenerative medicine researches. Especially for neural stem cell (NSC) transplantation, the uncontrollable differentiation of the NSCs in host often leads to a poor therapeutic effect in nerve tissue repair, such as spinal cord injury (SCI) repair. To address this issue, we have fabricated a conductive composite hydrogel (CCH) scaffold loading with NSCs by 3D bioprinting, for delivering the NSCs to injured spinal cord and repairing the propriospinal nerve circuit. In our strategy, a novel conductive polymer (PEDOT:CSMA,TA) was synthesized and introduced into a photocrosslinkable gelatin/polyethylene glycol physical-gel matrix, thereby forming a composite bioink with well shear-thinning and self-healing properties. The composite bioink we prepared was then printed into the NSC-laden CCH scaffold with high shape fidelity and similar physicochemical properties to native spinal cord tissues. The NSCs encapsulated in the bioprinted CCH scaffold extended their neurites to form superior physical contact with the neighboring cells as well as the electroconductive matrix, and maintained a predominant in vivo neuronal differentiation, accompanying with few astrocytic production in the lesion area after transplantation into the SCI sites. As a result, the removal of glial scar tissues and the regeneration of well-developed nerve fibres sequentially happened, which not only facilitated nerve tissue development, but also accelerated locomotor function recovery in the SCI rats. By exploring the application of conductive biomaterials in stem cell-based SCI therapy, this work represents a feasible, new approach to precisely construct tissue engineering scaffolds for stem cell-based therapy in traumatic SCI and other nervous system diseases.

Hydrogen regulates mitochondrial quality to protect glial cells and alleviates sepsis-associated encephalopathy by Nrf2/YY1 complex promoting HO-1 expression.

Sepsis-associated encephalopathy (SAE) is a complication of the central nervous system in patients with sepsis. Currently, no effective treatment for sepsis is available. Hydrogen plays a protective role in different diseases; however, the detailed mechanism of hydrogen-treated disease remains unclear. The purpose of this study was to investigate the effect of hydrogen on SAE in vitro and in vivo and the mechanism of hydrogen in mitochondrial dynamics and its function in astrocytes and microglia stimulated by lipopolysaccharides (LPSs). Animal models of SAE were generated by cecal ligation and puncture, and the SAE model was established by in vitro LPS stimulation. MTT, lactate dehydrogenase (LDH), reactive oxygen species (ROS), heme oxygenase-1 (HO-1) activity, mitochondrial membrane potential (MMP), and cell apoptosis assays were used to determine the effect of hydrogen on astrocytes and microglia stimulated by LPSs. The relationships between nuclear factor erythroid 2-related factor 2 (Nrf2), YY1, and HO-1 were examined by chromatin immunoprecipitation and co-immunoprecipitation. Mitochondrial homeostasis-related proteins in LPS-stimulated glial cells and brain tissues of SAE mice were detected by western blotting. The effects of hydrogen treatment in the SAE mouse model were investigated using Morris water maze and Y-maze analyses. After performing experiments with different concentrations of LPSs in vitro, we selected 1000ng/ml for subsequent experiments. Hydrogen attenuated the increase in ROS, LDH, and apoptosis and promoted decreases in cell activity and MMP, further promoting an increase in HO-1 expression induced by LPSs in astrocytes and microglia. Moreover, hydrogen further promoted the expression of Nrf2, HO-1, PGC-1α, TFAM, PARKIN, and PINK1, inhibited LPS-induced OPA1 and MFN2 expression in astrocytes and microglia, and downregulated the expression of DRP1 after LPS induction. Intriguingly, hydrogen treatment enhanced the binding between Nrf2 and YY1. However, silencing Nrf2 or YY1 abolished the protective effects of hydrogen on cell activity, LDH, ROS, and MMP; apoptosis; and regulation of Nrf2, HO-1, PGC-1α, TFAM, OPA1, DRP1, MFN2, PARKIN, and PINK1 in microglia. Finally, hydrogen treatment improved the results of behavioral detection, apoptosis, Nrf2, HO-1, PGC-1α, TFAM, OPA1, DRP1, MFN2, PARKIN, PINK1, and cytokines in SAE in vivo. Hydrogen improved cell injury and mitochondrial quality, which were associated with HO-1 expression promoted by the Nrf2/YY1 complex in vitro. Thus, hydrogen treatment may represent a novel therapeutic method for treating SAE.

Recognizing Brain Tumors Using Adaptive Noise Filtering and Statistical Features

The human brain, primarily composed of white blood cells, is centered on the neurological system. Incorrectly positioned cells in the immune system, blood vessels, endocrine, glial, axon, and other cancer-causing tissues, can assemble to create a brain tumor. It is currently impossible to find cancer physically and make a diagnosis. The tumor can be found and recognized using the MRI-programmed division method. It takes a powerful segmentation technique to produce accurate output. This study examines a brain MRI scan and uses a technique to obtain a more precise image of the tumor-affected area. The critical aspects of the proposed method are the utilization of noisy MRI brain images, anisotropic noise removal filtering, segmentation with an SVM classifier, and isolation of the adjacent region from the normal morphological processes. Accurate brain MRI imaging is the primary goal of this strategy. The divided section of the cancer is placed on the actual image of a particular culture, but that is by no means the last step. The tumor is located by categorizing the pixel brightness in the filtered image. According to test findings, the SVM could partition data with 98% accuracy.

Morphology of Serous Retinal Detachment in Morning Glory Optic Disc Anomaly in a Patient before and after Treatment with Systemic Carboanhydrase Inhibitors

Morning glory optic disc anomaly (MGODA) is a rare congenital defect of the optic nerve head. The optic nerve is enlarged, and its conical excavation is filled with glial tissue. It may be associated with cerebral malformations and ocular complications, whereas serous retinal detachment occurs in 38% of affected patients. Surgical treatment of detachment showed poor visual outcome in the past and conservative treatment options are scarce. A woman with MGODA presented in our clinic with sudden vision loss due to serous retinal detachment. She denied any previous ophthalmological problems and her past medical history was unremarkable. Vision testing showed normal visual acuity in her left eye and finger counting in her right eye. Slit lamp examination was unremarkable. Fundus examination of the right eye showed retinal detachment without holes or traction membranes and an enlarged optic disc with raised peripapillary tissue and glial tissue in the center of the optic disc. Due to the pathognomonic otpic disc finding, we diagnosed MGODA complicated by a serous retinal detachment. We treated the patient with systemic carboanhydrase inhibitors and documented the initial clinical findings as well as the course of disease under treatment by optical coherent tomography (OCT), fundus autofluorescence imaging (FAF), and visual field testing. During follow-up, we detected noticeable subretinal fluid regression and improvement in visual acuity. The application of oral carboanhydrase inhibitors appears to be a valid therapeutic option in patients with MGODA-associated serous macular detachment. OCT and FAF imaging are useful modalities for documentation of subretinal fluid regression and structural changes in the peripapillary region.

An unusal presentation of mature ovarian teratoma in a young girl: A rare case report

Introduction: Solid teratomas are relatively more common in infants and children (accounting for 15% of ovarian tumor). Though the peak age incidence is at second decade [1]. Metastatic implantation of glial tissue on surfaces of visceral or parietal peritoneum is called as Gliomatosis peritonei (GP) and its occurrence is very rare.Case Report: A 10 year old girl presented with the complaints of vague abdominal pain and discomfort for two months. Ultrasonography of the abdomen showed a heterogenous solid cystic tumor of 12 X 15 x 10 cm noted in left side of the ovary adherent to the fallopian tube. Left salpingoopherectomy was done and histopathology show features of mature solid ovarian teratoma with Gliomatosis peritonei.Conclusion: Gliomatosis peritonei is implantation of mature glial tissue on surfaces of peritoneum. It is often associated with ovarian teratoma of any grade. This is always present with massive peritoneal implantation, optimal resection is difficult. Although residual peritoneal disease can be totally quiescent over a long period, long-term follow-up is needed for patients with residual disease. A more conservative surgical approach may be carried out in patients with massive peritoneal spread.

Infectious Microorganisms Seen as Etiologic Agents in Parkinson’s Disease

Infections represent a possible risk factor for parkinsonism and Parkinson's disease (PD) based on information from epidemiology and fundamental science. The risk is unclear for the majority of agents. Moreover, the latency between infection and PD seems to be very varied and often lengthy. In this review, the evidence supporting the potential involvement of infectious microorganisms in the development of Parkinson's disease is examined. Consequently, it is crucial to determine the cause and give additional treatment accordingly. Infection is an intriguing suggestion regarding the cause of Parkinson's disease. These findings demonstrate that persistent infection with viral and bacterial microorganisms might be a cause of Parkinson's disease. As an initiating factor, infection may generate a spectrum of gut microbiota dysbiosis, engagement of glial tissues, neuroinflammation, and alpha-synuclein accumulation, all of which may trigger and worsen the onset in Parkinson's disease also contribute to its progression. Still uncertain is the primary etiology of PD with infection. The possible pathophysiology of PD infection remains a matter of debate. Furthermore, additional study is required to determine if PD patients develop the disease due to infectious microorganisms or solely since they are more sensitive to infectious causes.

Gliomatosis peritonei associated with mature cystic teratoma – A case report

The case report aims to highlight a rare entity called gliomatosis peritonei. We report a case of a 23-year-old female presenting with an ovarian mass along with multiple omental nodules. On histopathological examination, the ovarian mass was diagnosed as mature cystic teratoma and the omental nodules showed features of gliomatosis peritonei. Gliomatosis peritonei is a rare entity characterized by peritoneal or omental implants of mature glial tissue. GFAP (Glial Fibrillary Acidic Protein) was positive in the omental nodules. Gliomatosis peritonei is an exceptional finding and requires long term follow up of the patient.

EIF5A2 specifically regulates the transcription of aging-related genes in human neuroblastoma cells

BackgroundPost-transcriptional regulation plays a critical role in controlling biological processes such as aging. Previous studies have shown that eukaryotic initiation factor 5A (EIF5A) might play a crucial role in aging. It is unknown whether EIF5A2, a second isoform of EIF5A, could impact aging through post-transcriptional regulation.MethodsIn the present study, EIF5A2 overexpression (EIF5A2-OE) was induced in SH-SY5Y cells. RNA-seq, bioinformatics analysis and RT-qPCR validation experiments were then performed to explore the molecular mechanism of EIF5A2-mediated transcriptional regulation. Cell viability, proportion of senescent cells and the cell cycle were respectively determined by Cell Counting Kit-8, SA-β‑galactosidase and flow cytometry to evaluate the cell senescence.ResultsA total of 190 downregulated and 126 upregulated genes related to EIF5A2-OE were identified. Genes closely related to cellular aging processes such as unfolded protein response (UPR), cell adhesion and calcium signaling pathway were under global transcriptional regulation. Moreover, EIF5A2-OE promoted the viability of SH-SY5Y cells and reduced cell senescence in vitro. Among 30 genes with the most significant expression differences in EIF5A2-OE cells, we identified eight genes, including ASNS, ATF3, ATF4, CEBPB, DDIT3, HERPUD1, HSPA5 and XBP1, enriched in the UPR. Through EIF5A2-tanscription factors (TFs)-targets regulation network in EIF5A2-OE cells, we found three TFs, BHLHE40, RHOXF1 and TBX20, that targeted at these eight UPR-related genes. Verification test via the published database of human glial cell tissue showed only BHLHE40 and RHOXF1 were significantly associated with EIF5A2.ConclusionsOur findings suggest that EIF5A2 may alleviate cell senescence in vitro and mediate UPR-related genes via specific TFs. Thus, EIF5A2 could function as a regulator of aging via the regulation of transcription, which greatly expands the current understanding of the mechanisms of EIF5A2-mediated gene regulation.