Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Functional outcome of the low vision aids for visual impairment secondary to central nervous system tumors in children

To assess functional outcomes of optical low vision aids(LVAs) for pediatric visual impairment due to central nervous system(CNS) tumors. A prospective case study was conducted on 15 children with history of CNS tumors with mean age of 10.47±1.85 y. Lighthouse distance, near visual acuity tests, cycloplegic refraction, reading speed measurement and visual field examination were done. Prescription of far and near LVAs followed by training sessions. LVPrasad-functional vision questionnaire was done to evaluate performance. Visual impairment was moderate(13.3%), severe(73.3%), profound(6.7%) and near blindness in 6.7%. Telescopes prescribed in 33.4%, video magnifier in 46.7%. Questionnaire scores were significantly improved for distant rather than near tasks(P≤0.05) after training. LVAs rehabilitation is an effective method of improving vision in pediatric visual defects secondary to CNS tumors.

Inflammatory myofibroblastic tumor of the central nervous system:A case report

BACKGROUND An inflammatory myofibroblastic tumor(IMT)occurring in the central nervous system is very rare,and thus its pathogenesis is unknown.This case report and literature review aimed to explore the pathogenesis,clinical features,imaging findings,pathological characteristics,immunohistochemical characteristics,diagnoses,treatments,and risks of postoperative recurrence of IMT in the central nervous system.CASE SUMMARY A 67-year-old woman was admitted to the hospital with an exophthalmic protrusion and double vision in the left eye that had persisted for 3 mo.Magnetic resonance imaging(MRI)showed a 2.4 cm×1.3 cm heterogeneous large mass in the bottom of the left anterior cranial fossa,which was closely related to the dura mater.Before surgery,we suspected the mass to be meningioma.The entire mass was successfully removed under neuronavigation and electrophysiological monitoring,and postoperative pathology indicated an IMT with extensive infiltration of chronic inflammatory cells and scattered multinucleated giant cells.Head MRI at the 3-mo follow-up showed that the tumor at the bottom of left anterior cranial fossa had been completely resected without recurrence.CONCLUSION From the histological,immunohistochemical,and genetic analyses,the present case suggests that the pathogenesis of IMT-CNS is related to autoimmunity.

Analysis of Present Situation and Influencing Factors of Coping Methods by Parents of Children with Central Nervous System Tumors

Background: Central nervous system (CNS) tumors are the most common solid tumors among children. Due to the severity of the tumors and the complexity of therapeutic regimes, it is very important to examine whether parents of the children with CNS tumors have positive coping methods against the disease. This study aims to analyze the coping methods of the parents and the factors influencing the methods. Methods: A total of 108 parents of brain cancer children admitted from January 2019 to September 2020 were selected as subjects. After collecting the general information of the parents, they were studied using the Coping Health Inventory for Parents (CHIP, Chinese version). Additionally, their coping pattern and the influencing factors were analyzed. Results: The average scores of the three subscales of the CHIP were (4.25 ± 0.939), (3.11 ± 1.205) and (3.60 ± 1.187), respectively. Univariate analysis showed that parents’ education, medical payment methods, places of residence and economic concerns were the main factors influencing the coping methods (all P < 0.05). Conclusions: Healthcare staff should fully evaluate the coping methods adopted by the parents having children with CNS tumors, take targeted nursing measures accordingly, and assist the parents in seeking social support and learning disease-related knowledge. In addition, public education on disease is equally important.

Cell Replication and Angiogenesis in Central Nervous System Tumors and Their Relationship with the Expression of Tissue Prolactin and Hyperprolactinemia

This study aimed to assess the effect of intracellular prolactin (ICPRL) and hyperprolactinemia on cell replication, using an immunohistochemical (IHC) technique for Ki-67 and Mcm-2, and angiogenesis, using IHC for endoglin CD-105, in central nervous system (CNS) tumors. This cross-sectional study included 79 cases of surgically excised primary CNS tumors of neuroepithelial origin (41.8% of all cases: 10.2% astrocytomas, 24% glioblastomas and 7.6% oligodendrogliomas) and meningeal origin (58.2% of all cases). Ki-67 and Mcm-2 indexes were calculated as a percentage of marked cells. The medians for Ki-67 and Mcm-2 indexes were significantly lower in meningiomas than in glioblastomas (p S = 0.60) replication markers. There were no significant differences in vascular density between the different histological types. Immunohistochemistry for ICPRL was positive in 45.6% of the tumors. Serum prolactin (PRL) was elevated in 30.6% of the cases. Multiple regression analysis revealed no important correlation of ICPRL and serum PRL on Ki-67 and Mcm-2 indexes or vascular density. The analysis of the combined impact of ICPRL and serum PRL variables revealed a trend towards an increase in microvessel density in tumor tissue and a significant increase in cell replication markers (p = 0.009 for Ki-67 and p = 0.05 for Mcm-2). PRL in tumor tissue may be one of the modulating factors of cell proliferation in the CNS.

Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling

Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis.Glioblastoma,the most common primary tumor in adults,is associated with poor survival and remains one of the least treatable neoplasms.These tumors are highly heterogenous and complex in their nature.Due to this complexity,traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’behavior in vivo.Two-dimensional models lack the spatial arrangement,the heterogeneity in cell types,and the microenvironment that play a large role in tumor cell behavior and response to treatment.Recently,scientists have turned towards three-dimensional culturing methods,namely spheroids and organoids,as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts.Moreover,tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing.In this review,we will discuss the current available literature on in vitro threedimensional culturing models in CNS tumors,in addition to presenting their advantages and current limitations.We will also elaborate on the future implications of these models and their benefit in the clinical setting.

B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma

To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.RESULTSB2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.CONCLUSIONB2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.

Central pancreatectomy:a new technique for resection of selected pancreatic tumors

BACKGROUND:Pancreatic tumors located in the neck region usually require pancreaticoduodenectomy or splenopancreatectomy.For small benign tumors enucleation is not usually feasible due to their size and localization;then pancreatectomy is often needed.Central pancreatectomy consists of a limited resection of the midportion of the pancreas and can be offered in benign and low-grade malignant tumors of the neck of the pancreas.The study aimed to evaluate whether central pancreatectomy has a place in pancreatic surgery. METHODS:In this study,which covered a period of 14 months,we performed central pancreatectomy in four selected patients.Preoperative evaluation and operative frozen section biopsy in indicated cases allowed proper selection for the procedure.Operative details,complications and follow-up were recorded. RESULTS:Four patients,two with serous cystadenoma,and one with an islet cell tumor,and one with a hydatid cyst, were identified for the procedure.The mean tumor size was 3 cm,the mean operative time was 217.5 minutes,and the mean blood loss was 382.5 ml.There was no morbidity or mortality in this series.No endocrine or exocrine deficiency was observed in any patient during a mean follow-up of 22.7 months. CONCLUSIONS:Central pancreatectomy is a procedure that offers excellent results in benign and low-grade malignant tumors.It preserves functional elements(endocrine and exocrine)of the pancreas and also eliminates the infective and hematological effects of splenectomy.Thus,central pancreatectomy should be included in the armamentarium of pancreatic surgery,and in order to obtain good results,proper indications and adequate experience are recommended.

Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases

Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.

Metastatic pancreatic solitary fibrous tumor: A case report

BACKGROUND Solitary fibrous tumor(SFT)is a rare mesenchymal tumor that is most commonly found in the pleura but can also originate from non-pleural sites.Among the nonpleural localizations,the pancreas is extremely rare.In particular,metastasis to the pancreas from the central nervous system(CNS)is extremely rare,with only two cases reported so far.We report a case of recurrence in the pancreas 14 years after the initial complete surgical removal of a tumor in the CNS.CASE SUMMARY A 68-year-old man with a past medical history of recurrent meningeal hemangiopericytoma,currently referred to as SFT,presented to the hospital with jaundice.The patient was first diagnosed with an 8cm-sized meningeal hemangiopericytoma fourteen years ago and underwent osteoplastic craniotomy.After 16 mo,imaging showed recurrence and he underwent gamma knife radiosurgery(GKRS).2 years later,imaging showed recurrence again leading to a second GKRS.5 years later,recurrence was again suspected leading to a second craniotomy.Since then 3 years had passed,and imaging showed a 3.5cm-sized mass lesion on the pancreatic head with obstruction of the pancreatic and bile ducts.Endosonography with fine-needle aspiration biopsy was done preoperatively and aided in the diagnosis of SFT.The patient underwent pyloruspreserving pancreaticoduodenectomy.Pathologic findings of the resected pancreatic specimen,consistent with the previously resected brain specimen,confirmed the diagnosis of SFT.CONCLUSION The rarity and lack of knowledge about SFTs make suspecting and diagnosing this disease challenging.We believe that a report of metastatic pancreatic SFT from the CNS will contribute to a better understanding of this rare disease.

Malignant Meningioma: Two Cases Observed at the Hospital Center of Soavinandriana, Antananarivo

Introduction: Meningiomas are tumors formed by arachnoid cells, typically attached to the inner surface of the dura mater. Malignant forms are rare and no case has been reported in the Malagasy literature. The objective of our study is to report two Malagasy cases of malignant meningioma and to discuss the epidemiological and anatomical-clinical particularities of this tumor. Observation: The first patient, a 41-year-old woman, presented with a rapidly progressive intracranial hypertension syndrome. The patient had undergone surgery two years earlier for a grade II meningioma and had no family history of meningioma, neurofibromatosis, or personal history of brain irradiation or head trauma. Her brain scan showed a heterogeneous polylobed left parieto-occipital mass with a meningeal implantation base. The anatomopathological examination of the samples revealed a malignant meningioma. The second patient was a 33-year-old man, operated for grade I meningioma eleven months before admission, with no other personal or family history. The patient was hospitalized for tumor recurrence with signs of intracranial hypertension. The brain computed tomography (CT) scan showed a heterogeneous extra-axial tumor in right temporo-parietal lobe. Surgical excision was performed. On histological examination, a proliferation of tumor cells of meningothelial appearance with papillary architecture was observed, leading to the diagnosis of malignant meningioma. Conclusion: Malignant meningioma is a rare and serious entity. The clinical manifestations are nonspecific and imaging may mimic a low-grade meningioma. The diagnosis of certainty is histological and is based on essentially morphological criteria. The latter condition the overall survival of the patient and the therapeutic conduct.

Epidemiological characteristics of central nervous system tumors in children: a 5-year review of 3180 cases from Beijing Tiantan Hospital

Background:To describe the epidemiological characteristics of central nervous system(CNS)tumors in children,based on the neurosurgery department of Beijing Tiantan Hospital.Methods:From January 2015 to December 2019,3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization(WHO)classification of tumors.Patients were 0 to 15 years old.We analyzed age-related gender preferences,tumor locations,and the histological grades of the tumors.In addition,the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies.Results:In this study,intracranial and spinal tumors account for 96.4%(3066)and 3.6%(114)of all tumors,with a preponderance of supratentorial tumors(57.9%).Among all pediatric patients,low-grade tumors comprise 67.1%(2135).The integral gender ratio of males to females is 1.47:1 and the average age of patients is 7.59 years old.The five most common intracranial tumors are craniopharyngioma(15.4%),medulloblastoma(14.3%),pilocytic astrocytoma(11.8%),diffuse astrocytoma(9.8%),and anaplastic ependymoma(4.8%).Conclusions:Due to the lack of national data on childhood brain tumors,we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China.We analyzed the data of the past 5 years,reflecting the incidence of CNS tumors in Chinese children to a certain extent,and laying a data foundation for subsequent clinical studies.

A 5-year-old child presenting with tumor-like primary angiitis of the central nervous system

Introduction:Primary angiitis of the central nervous system(PACNS)is a vasculitis confined to the CNS.A small proportion of the lesions may present as a tumor-like mass,which is rarely seen in children.Case presentation:A 5-year-old girl was admitted to our hospital because of an intermittent headache.Brain imaging suggested a space-occupying lesion in the right cerebral hemisphere.The final diagnosis was PACNS with a lymphocytic pattern by stereotactic brain biopsy.Her condition improved after immunotherapy.Conclusion:Pediatricians should consider the possibility of PACNS when encountering intracranial tumor-like lesions.Early diagnosis of tumor-like PACNS and prompt immunotherapy could improve the long-term prognosis and avoid surgery.

Neurocutaneous melanosis with an intracranial cystic-solid meningeal melanoma in an adult:A case report and review of literature

BACKGROUND Neurocutaneous melanosis(NCM)is a rare congenital,nonhereditary neurocutaneous syndrome that mainly occurs in children;adult NCM is very rare.Due to its rarity,the clinical features and treatment strategies for NCM remain unclear.The purpose of this study was to explore the clinical features,diagnosis,treatment and prognosis of NCM in adults.Most intracranial meningeal melanomas are solid masses,and cystic-solid malignant melanomas are very rare.Due to the lack of data,the cause of cystic changes and the effect on prognosis are unknown.CASE SUMMARY A 41-year-old woman was admitted to the hospital with intermittent headache for 1 mo.Magnetic resonance imaging(MRI)showed a 4.7 cm×3.6 cm cystic-solid mass in the left temporal lobe with peritumoral edema.The entire mass was removed,and postoperative pathology indicated malignant melanoma.CONCLUSION MRI is the first-choice imaging approach for diagnosing central nervous system diseases in NCM patients,although cerebrospinal fluid may also be used.At present,there is no optimal treatment plan;gross total resection combined with BRAF inhibitors and MEK inhibitors might be the most beneficial treatment.

Challenges and opportunities for managing pediatric central nervous system tumors in China

Central nervous system(CNS)tumors represent the most deadly cancer in pediatric age group.In China,thousands of children are diagnosed with CNS tumors every year.Despite the improving socioeconomic status and availability of medical expertise within the country,unique challenges remain for the delivery of pediatric neuro-oncology service.In this review,we discuss the existing hurdles for improving the outcome of children with CNS tumors in China.Need for precise disease burden estimation,lack of intra-and inter-hospital collaborative networks,high probability of treatment abandonment,along with financial toxicities from treatment represent the key challenges that Chinese healthcare providers encounter.The tremendous opportunities for advancing the status of pediatric neuro-oncology care in and beyond the country are explored.

Temporal dynamic changes of connexin 43 expression in C6 cells following lipopolysaccharide stimulation

Connexin 43, a gap junction protein, is expressed mainly in glia in the central nervous system. Neuroinflammation plays an important role in central nervous system injury. Changes to glial connexin 43 levels and neuroinflammation may trigger brain injury and neurodegenerative diseases To illustrate the relationship between connexin 43 and neuroinflammation, this study investigated how connexin 43 expression levels change in lipopolysaccharide-stimulated rat C6 glioma cells. C6 cells were treated with 0.05, 0.25, 0.5, 1,2.5 and 5 IJg/mL lipopolysaccharide for 24 hours. The nitrite estimation-detected nitric oxide release level was elevated substantially after lipopolysaccharide stimulation. To test the transcriptional level changes of inducible nitric oxide synthase, tumor necrosis factor-a and connexin 43 mRNA, C6 cells were treated with 5 pg/mL lipopolysaccharide for 3 48 hours. Reverse transcription-PCR showed that the expression of inducible nitric oxide synthase and tumor necrosis factor-a mRNA increased over time, but connexin 43 mRNA levels increased in lipopolysaccharide-stimulated C6 cells at 3 and 6 hours, and then decreased from 12 to 48 hours. Connexin 43 protein expression was detected by immunofluorescence staining, and the protein levels matched the mRNA expression levels. These results suggest that connexin 43 expression is biphasic in lipopo^ysacchadde-induced neuroinflammation in C6 cells, which may be correlated with the connexin 43 compensatory mechanism.

Interdisciplinary management of central nervous system metastasis and neoplastic meningitis:recent developments and future perspectives

The incidence of metastatic disease in the central nervous system(CNS)is rising.According to current estimates,up to a third of adult cancer patients will suffer from CNS metastasis.Clinical evidence-based data from prospective randomized trials are rare,however,because CNS metastasis patients were often excluded from clinical trial participation.The management of CNS metastasis patients is therefore rather ill-defined and an interdisciplinary challenge.Recent basic and translational science data have begun contributing to a more profound understanding of the molecular mechanisms leading to invasion of tumor cells into the CNS.This report reviews advances,challenges,and perspectives in this field.

Research progress on circulating tumor cell detection in brain gliomas

Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.