scholarly journals Treatment of the bone marrow stromal stem cell supernatant by nasal administration—a new approach to EAE therapy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xi Wang ◽  
Wantong Zhai ◽  
Jiahui Zhu ◽  
Wei Zhao ◽  
Xiaoyi Zou ◽  
...  

Abstract Introduction Multiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). CNS has its own unique structural and functional features, while the lack of precision regulatory element with high specificity as therapeutic targets makes the development of disease treatment in the bottleneck. Recently, the immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). However, the administration route and the safety evaluation limit the application of BMSC. In this study, we investigated the therapeutic effect of BMSC supernatant by nasal administration. Methods In the basis of the establishment of the EAE model, the BMSC supernatant were treated by nasal administration. The clinical score and weight were used to determine the therapeutic effect. The demyelination of the spinal cord was detected by LFB staining. ELISA was used to detect the expression of inflammatory factors in serum of peripheral blood. Flow cytometry was performed to detect pro-inflammatory cells in the spleen and draining lymph nodes. Results BMSC supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors. As a new, non-invasive treatment, there are no differences in the therapeutic effects between BMSC supernatant treated by nasal route and the conventional applications, i.e. intraperitoneal or intravenous injection. Conclusions BMSC supernatant administered via the nasal cavity provide new sights and new ways for the EAE therapy.

Author(s):  
Ezzatollah Keyhani

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.


2008 ◽  
Vol 173 (6) ◽  
pp. 1669-1681 ◽  
Author(s):  
Sonja Hochmeister ◽  
Manuel Zeitelhofer ◽  
Jan Bauer ◽  
Eva-Maria Nicolussi ◽  
Marie-Therese Fischer ◽  
...  

2021 ◽  
Vol 15 ◽  
Author(s):  
Sam Joshva Baskar Jesudasan ◽  
Somnath J. Gupta ◽  
Matthew A. Churchward ◽  
Kathryn G. Todd ◽  
Ian R. Winship

Microglia are the primary cells in the central nervous system that identify and respond to injury or damage. Such a perturbation in the nervous system induces the release of molecules including ATP and glutamate that act as damage-associated molecular patterns (DAMPs). DAMPs are detected by microglia, which then regulate the inflammatory response in a manner sensitive to their surrounding environment. The available data indicates that ATP and glutamate can induce the release of pro inflammatory factors TNF (tumor necrosis factor), IL-1β (interleukin 1 beta), and NO (nitric oxide) from microglia. However, non-physiological concentrations of ATP and glutamate were often used to derive these insights. Here, we have compared the response of spinal cord microglia (SM) relative to brain microglia (BM) using physiologically relevant concentrations of glutamate and ATP that mimic injured conditions in the central nervous system. The data show that ATP and glutamate are not significant modulators of the release of cytokines from either BM or SM. Consistent with previous studies, spinal microglia exhibited a general trend toward reduced release of inflammatory cytokines relative to brain-derived microglia. Moreover, we demonstrate that the responses of microglia to these DAMPs can be altered by modifying the biochemical milieu in their surrounding environment. Preconditioning brain derived microglia with media from spinal cord derived mixed glial cultures shifted their release of IL-1ß and IL-6 to a less inflammatory phenotype consistent with spinal microglia.


2020 ◽  
Author(s):  
Sam Joshva Baskar Jesudasan ◽  
Somnath J Gupta ◽  
Matthew A Churchward ◽  
Kathryn Todd ◽  
Ian R Winship

AbstractMicroglia are the primary cells in the central nervous system that identify and respond to injury or damage. Such a perturbation in the nervous system induces the release of molecules including ATP and glutamate that act as damage-associated molecular patterns (DAMPs). DAMPs are detected by microglia, which then regulate the inflammatory response in a manner sensitive to their surrounding environment. The available data indicates that ATP and glutamate can induce the release of pro inflammatory factors TNF (tumor necrosis factor), IL-1β (interleukin 1 beta) and NO (nitric oxide) from microglia. However, non-physiological concentrations of ATP and glutamate were often used to derive these insights. Here, we have compared the response of spinal cord microglia (SM) relative to brain microglia (BM) using physiologically relevant concentrations of glutamate and ATP that mimic injured conditions in the central nervous system. The data show that ATP and glutamate are not significant modulators of the release of cytokines from either BM or SM. Consistent with previous studies, spinal microglia exhibited a general trend towards reduced release of inflammatory cytokines relative to brain-derived microglia. Moreover, we demonstrate that the responses of microglia to these DAMPs can be altered by modifying the biochemical milieu in their surrounding environment. Preconditioning brain derived microglia with media from spinal cord derived mixed glial cultures shifted their release of IL-ß, IL-6 and IL-10 to a less inflammatory phenotype consistent with a spinal microglia.


2021 ◽  
Author(s):  
Rafael Bragança Rodrigues Matias ◽  
Bruna Cardoso de Mattos Boccalini ◽  
Renata de Oliveira Costa ◽  
Maria Fernanda Mélega Mingossi

Introduction: Mantle cell lymphoma (MCL) is a subtype of uncommon nonHodgkin lymphoma. The involvement of the central nervous system (CNS) is uncommon in the course of the disease. Objective: To report a case of recurrence of MCL in the CNS as the first manifestation, after chemotherapy and bone marrow transplantation. Case report: Male patient, 49 years old, with no previous comorbidities diagnosed with stage IV MCL (bone marrow), submitted to chemotherapy and autologous transplantation. After two years, he sought out the neurology clinic with a complaint of blurred vision. Neurological examination: without motor deficit; bilateral partial ptosis, bilateral divergent strabismus, tongue shift to the right. CSF with 230 leukocytes/mm³, 70% of lymphocytes, glucose of 71 mg /dl and protein of 85 mg /dl; Skull MRI demonstrated bilateral and symmetrical enhancement of segments of the cisterns of the optic and oculomotor nerves; Trigeminal, facial, vestibulocochlear and glossopharyngeal, vagus and accessory nerves more exuberant on the left. CSF immunophenotyping showed CD19, CD5 and Kappa positive monoclonal, compatible with MCL recurrence. Intrathecal and systemic chemotherapy with methotrexate were initiated. Discussion: Risk of recurrence of MCL and infiltration of the CNS is uncommon (3.9 - 5%). The patient did not show any signs of systemic involvement, only the neurological findings, which is atypical since the neurological presentation is more associated with recurrence of MCL with a course of systemic findings. Conclusion:The authors point out that in patients with treated MCL who have neurological manifestations without systemic findings, tumor recurrence should be considered.


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