R. Davis, D. Buck, K. McCracken, G. W. Cox, Subhas Das
{"title":"Interleukin-1β-induced inflammatory signaling in C20 human microglial cells","authors":"R. Davis, D. Buck, K. McCracken, G. W. Cox, Subhas Das","doi":"10.20517/2347-8659.2018.60","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.60","url":null,"abstract":"Aim: Increased inflammatory signaling in microglia is implicated in the pathogenesis of neurodegenerative diseases, trauma, psychiatric disorders, and anxiety/depression. Understanding inflammatory signaling in microglia is critical for advancing treatment options. Studying rodent-derived microglia has yielded substantial information, yet, much remains to better understand inflammatory signaling in human microglia. Hence, there is great interest in developing immortalized human microglial cell lines. The C20 human microglial cell line was recently developed and our primary objective was to advance our knowledge of inflammatory signaling in these cells. Methods: Expression of the microglia specific marker transmembrane protein 119 (TMEM119) was assessed by western blot analysis. Lipopolysaccharide (LPS)and interleukin-1β (IL-1β)-induced cytokine/chemokine expression was determined by ELISA. Phosphorylation of inhibitory kappa B alpha (IκBα), nuclear factor (NF)-κB p65, and p38 mitogen-activated protein kinase (p38 MAPK) was measured by western blot analysis. Results: TMEM119 was expressed in unstimulated C20 cells, and to a greater extent in IL-1β-stimulated cells. IL-1β significantly induced IL-6, monocyte chemoattractant protein-1/CCL2, and interferon-γ inducible protein 10/CXCL10 expression. LPS induced CCL2 expression, but not IL-6 or CXCL10 expression. IL-1β induced inflammatory signaling as indicated by increased phosphorylation of IκBα, NF-κB p65 and p38 MAPK. Conclusion: We provide the first evidence that C20 microglia express TMEM119. This is the initial report of IL-1βinduced activation of IκBα, NF-κB p65, and p38 MAPK and subsequent CXCL10, CCL2 and IL-6 secretion in C20 cells. These findings advance our understanding of inflammatory signaling in C20 cells and support the value of this cell line as a research tool.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44224249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy vs. multiple sclerosis. Either one or sometimes both?","authors":"G. Paraskevas, V. Constantinides, E. Kapaki","doi":"10.20517/2347-8659.2018.50","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.50","url":null,"abstract":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), is the most common cause of inherited cerebral small vessel disease, inherited stroke and inherited vascular dementia. It is not infrequent for CADASIL to be mistaken and mistreated for multiple sclerosis (MS). A much less frequent but existing scenario is the co-occurrence of CADASIL and MS (or MS-like inflammatory condition). Such patients may present with spinal cord lesions, brain or spinal cord enhancing lesions, positive oligoclonal bands and high IgG index in the cerebrospinal fluid and good response to corticosteroids or immunomodulating treatments. CADASIL through various mechanisms may trigger or modulate autoimmune reactions, and either be complicated by an inflammatory component or cause an MS-like disorder.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48188318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Almedallah, Gada Alsaffar, Ghadeer Al-Shabeeb, A. Baarmah, E. Nassim
{"title":"Paraneoplastic limbic encephalitis associated with testicular mixed germ cell tumor","authors":"D. Almedallah, Gada Alsaffar, Ghadeer Al-Shabeeb, A. Baarmah, E. Nassim","doi":"10.20517/2347-8659.2018.55","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.55","url":null,"abstract":"Paraneoplastic limbic encephalitis (PLE) is a rare immunopathological syndrome, reported in association with certain types of malignancies. Patients present with cognitive and memory impairments, disordered perception, mood and behavioral changes, sleep disturbances, and seizures. Despite the growing number of cases being reported, it still poses a diagnostic challenge. We encountered a patient with a myriad of neuropsychiatric symptoms who exhibited a highly variable response to therapy. A 36-year-old male presented with memory impairment, excessive sleepiness, and slurred speech. Brain magnetic resonance imaging revealed hyperintensities in the temporal lobes and hypothalamus, all suggestive of limbic encephalitis. He was found to have a mixed germ cell testicular teratoma. Screening for commonly associated antibodies did not yield positive results, which emphasizes that sero-negative PLE can be missed in patients with malignancies. In reporting this case, we urge neurologists to consider PLE as part of the differential diagnosis in similar ambiguous clinical scenarios.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41863878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clairice Pearce, M. Chrostek, Emily G. Fellows, Nikolas G. Toman, Sarah K. Tran, A. Crane, W. Low
{"title":"Immunotherapy and checkpoint inhibitors for gliomas","authors":"Clairice Pearce, M. Chrostek, Emily G. Fellows, Nikolas G. Toman, Sarah K. Tran, A. Crane, W. Low","doi":"10.20517/2347-8659.2018.46","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.46","url":null,"abstract":"Glioma treatments are faced with challenges, including the inability to fully eliminate cancer stem cells, the immunosuppressive tumor microenvironment, and the blood brain barrier. Although progress has been made with surgical, radiation, and chemotherapies, prognosis for patients remains poor. Rapidly emerging immunotherapies may be able to address the challenges that conventional techniques cannot. Immunotherapies manipulate the patient’s immune system to selectively combat malignancies. Therapies often work to enhance T-cell and natural killer (NK) cell function, which can both eliminate tumor cells and enhance remission. Vaccines encourage in vivo development of anti-tumor T-cells and NK cells, while adoptive transfer techniques focus on engineering immune cells ex vivo before reintroducing them to patients. Vaccine and adoptive transfer therapies have been shown to induce enhanced immune responses in patients but have not always correlated with improved outcomes, likely because of the tumor immunosuppressive microenvironment. Checkpoint inhibitors can impair these tumor immunosuppressive capabilities. Although no one treatment has been able to consistently eliminate gliomas and maintain remission, combinations of vaccines or adoptive transfer techniques in conjunction with immune checkpoint inhibitors offers promise.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45990985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors","authors":"S. Gururangan, E. Sayour, D. Mitchell","doi":"10.20517/2347-8659.2018.44","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.44","url":null,"abstract":"The therapeutic approach of adoptive lymphocyte transfer (ALT) using lymphocytes primed and expanded ex-vivo by exposure to total tumor RNA (ttRNA) containing dendritic cells (DCs) and administered after lymphodepletive host conditioning in patients with refractory melanoma with brain metastases has shown excellent objective responses indicating that the central nervous system (CNS) is not an immune privileged site and further paved the way for utilization of a similar approach in other cancers. We have shown that the use of ALT + ttRNA DCs following either myeloablative or non-myeloablative host conditioning is feasible and safe and appears to prolong survival in a proportion of children with recurrent medulloblastoma who had failed standard cytotoxic therapy. Further refinements in this promising approach are needed to improve outcomes and extend this treatment to a broad range of CNS malignancies.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41653572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexsey V. Raevsky, M. Sharifi, V. Pinchuk, A. Klegeris
{"title":"Correction: In silico design of novel gold-phosphate containing compounds as selective inhibitors of cathepsin B in neuroinflammation","authors":"Alexsey V. Raevsky, M. Sharifi, V. Pinchuk, A. Klegeris","doi":"10.20517/2347-8659.2018.61","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.61","url":null,"abstract":"","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47148284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akanksha Sharma, Gustavo De Leon, A. Porter, Marie F. Grill, A. Rosenthal, Christine E. Brown, K. Swanson, M. Mrugala
{"title":"CAR-T cell therapy in neuro-oncology: applications and toxicity","authors":"Akanksha Sharma, Gustavo De Leon, A. Porter, Marie F. Grill, A. Rosenthal, Christine E. Brown, K. Swanson, M. Mrugala","doi":"10.20517/2347-8659.2018.51","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.51","url":null,"abstract":"A new era for cancer treatment has been ushered in with the field of cancer immunotherapy. After initial success with systemic malignancies, several of these promising treatments are being investigated for efficacy with primary and secondary brain tumors. Chimeric antigen receptor (CAR) T cells are being studied, both with systemic infusion and direct administration to the tumor and into the cerebrospinal fluid, with promising early results. Systemic CAR-T treatment can have serious systemic and neurological toxicities that are important for the practicing neurologist and neuro-oncologist to know and understand. This review aims to discuss adoptive cell therapies with a focus on CAR-T treatment. We review use of this therapy in brain cancers, particularly malignant glioma, and provide an overview of the toxicity of CAR-T treatment and its appropriate management.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41244972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Choi, N. Mai, Christopher M. Jackson, Z. Belcaid, M. Lim
{"title":"It takes two: potential therapies and insights involving microglia and macrophages in glioblastoma","authors":"John Choi, N. Mai, Christopher M. Jackson, Z. Belcaid, M. Lim","doi":"10.20517/2347-8659.2018.47","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.47","url":null,"abstract":"Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia and macrophages, despite a growing body of evidence that demonstrates key structural and functional differences between the cell types. Furthermore, the current M1/M2 paradigm used to sub-classify microglia and macrophages has proven to be incomplete at best, with the growing amount of in vivo and genomic data incompatible with this dichotomy. Finally, a number of studies have already established that in the setting of the GBM tumor microenvironment, both microglia and macrophages are complicit in tumor progression. This review highlights the differences between microglia and macrophages, particularly in the context of GBM, and discusses at length several potential therapeutic strategies made possible by understanding specific pro-tumor and anti-tumor pathways in these myeloid populations. Ultimately, investigating the differences between microglia and macrophages offers insight into the progression of GBM, its marked resistance to current immunotherapy regimens, and future directions for new treatment modalities.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48969856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Darbinyan, M. Antonyan, H. Koshatashyan, Susanna S. Gevorgyan, H. Arestakesyan, Z. Karabekian, N. Ayvazyan, A. Voskanyan
{"title":"Changes in microglia activity of rat brain induced by Macrovipera lebetina obtusa venom","authors":"A. Darbinyan, M. Antonyan, H. Koshatashyan, Susanna S. Gevorgyan, H. Arestakesyan, Z. Karabekian, N. Ayvazyan, A. Voskanyan","doi":"10.20517/2347-8659.2018.33","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.33","url":null,"abstract":"Aims: The microglia activity of rat brain following exposure of the Macrovipera lebetina obtusa venom was investigated. Methods: Histochemical analysis of brain microcirculatory bed staining by Ca ATPase method for variable doses after intraperitoneal injections given for different time periods was used. The hemorrhagic activity of snake venom metalloproteinases was tested. Toxicological data were calculated using Behrens and Miller-Tainter methods. Surface, size of brain microglial cells (MGCs) and staining intensity were quantified using ImageJ software. Results: The vasodestructive action of the venom resulted in changes in ATPase activity. The intensity of staining of rat brain microcirculatory bed was venom dose-, and time-dependent. Increased activity of MGCs in hemorrhagic loci of different regions of venom affected brain was also demonstrated. Conclusion: The activation of microglia and changes of its form, size, and position strongly correlates with hemorrhage-induced cerebrovascular damage.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44373929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Presynaptic mechanisms at prefrontal synapses involved in persistent pain","authors":"H. Toyoda","doi":"10.20517/2347-8659.2018.48","DOIUrl":"https://doi.org/10.20517/2347-8659.2018.48","url":null,"abstract":"The cumulative evidence from animal and human studies revealed that the anterior cingulate cortex (ACC) plays essential roles in pain sensation and persistent pain. It has been evident in the ACC synapses of animals that changes in both the presynaptic and postsynaptic function are caused by peripheral nerve injury. Thus far, postsynaptic changes in the ACC following nerve injury have been primarily studied to understand the mechanisms of chronic pain. In recent years, studies focusing on the presynaptic mechanisms in chronic pain have been progressively increased. In this review, I will discuss molecular mechanisms associated with chronic pain and presynaptic form of long-term potentiation. I will also discuss evidence for presynaptic changes in the ACC caused by disease-related pain.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44809953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}