scholarly journals Brain-to-cervical lymph node signaling after stroke

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Elga Esposito ◽  
Bum Ju Ahn ◽  
Jingfei Shi ◽  
Yoshihiko Nakamura ◽  
Ji Hyun Park ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Cerebral Ischemia ◽  
Systemic Inflammation ◽  
Cervical Lymph Node ◽  
Inflammatory Responses ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Surgical Removal ◽  
Lymphatic Endothelial Cells

AbstractAfter stroke, peripheral immune cells are activated and these systemic responses may amplify brain damage, but how the injured brain sends out signals to trigger systemic inflammation remains unclear. Here we show that a brain-to-cervical lymph node (CLN) pathway is involved. In rats subjected to focal cerebral ischemia, lymphatic endothelial cells proliferate and macrophages are rapidly activated in CLNs within 24 h, in part via VEGF-C/VEGFR3 signalling. Microarray analyses of isolated lymphatic endothelium from CLNs of ischemic mice confirm the activation of transmembrane tyrosine kinase pathways. Blockade of VEGFR3 reduces lymphatic endothelial activation, decreases pro-inflammatory macrophages, and reduces brain infarction. In vitro, VEGF-C/VEGFR3 signalling in lymphatic endothelial cells enhances inflammatory responses in co-cultured macrophages. Lastly, surgical removal of CLNs in mice significantly reduces infarction after focal cerebral ischemia. These findings suggest that modulating the brain-to-CLN pathway may offer therapeutic opportunities to ameliorate systemic inflammation and brain injury after stroke.

scholarly journals HIV-1 Matrix Protein p17 Promotes Lymphangiogenesis and Activates the Endothelin-1/Endothelin B Receptor Axis

2014 ◽  
Vol 34 (4) ◽  
pp. 846-856 ◽  
Author(s):  
Francesca Caccuri ◽  
Christine Rueckert ◽  
Cinzia Giagulli ◽  
Kai Schulze ◽  
Daniele Basta ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Structure Formation ◽  
Highly Active Antiretroviral Therapy ◽  
Matrix Protein ◽  
Lymphatic Endothelial Cells ◽  
Endothelin 1 ◽  
Tumor Dissemination ◽  
Hiv 1

Objective— AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Approach and Results— Human primary lymph node–derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node–derived lymphatic endothelial cells and activating the Akt/extracellular signal–regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node–derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Conclusions— Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.

scholarly journals Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

2005 ◽  
Vol 2 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Masamitsu Shimazawa ◽  
Satomi Chikamatsu ◽  
Nobutaka Morimoto ◽  
Satoshi Mishima ◽  
Hiroichi Nagai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Folk Medicine ◽  
Neuroprotective Function ◽  
Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

scholarly journals Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis

Immunity ◽  
2017 ◽  
Vol 47 (1) ◽  
pp. 80-92.e4 ◽  
Author(s):  
Lucas Onder ◽  
Urs Mörbe ◽  
Natalia Pikor ◽  
Mario Novkovic ◽  
Hung-Wei Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymphatic Endothelial Cells

3-Aminobenzamide reduces brain infarction and neutrophil infiltration after transient focal cerebral ischemia in mice

2003 ◽  
Vol 184 (2) ◽  
pp. 973-980 ◽  
Author(s):  
Jérôme Y Couturier ◽  
Li Ding-Zhou ◽  
Nicole Croci ◽  
Michel Plotkine ◽  
Isabelle Margaill
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Neutrophil Infiltration ◽  
Transient Focal Cerebral Ischemia

Involvement of Erythropoietin Expression in Acupuncture Preconditioning-Induced Ischemic Tolerance

2012 ◽  
Vol 554-556 ◽  
pp. 1650-1655 ◽  
Author(s):  
Xue Mei Han ◽  
Hong Tao Wei ◽  
Song Yan Liu
Keyword(s):  
Endothelial Cells ◽  
In Situ Hybridization ◽  
Cerebral Ischemia ◽  
Vascular Endothelial Cells ◽  
Focal Cerebral Ischemia ◽  
Peripheral Zone ◽  
Vascular Endothelial ◽  
Neuroprotective Effects ◽  
Protein Expressions

Abstract Objective To investigate the expression of erythropoietin (EPO) after acupuncture preconditioning plus focal cerebral ischemia treatment. Methods Rat focal cerebral ischemia model and acupuncture preconditioning model were established. Animals were randomly assigned into different groups: control (focal cerebral ischemia) and acupuncture preconditioning plus focal cerebral ischemia, with 8 rats for each group. The expression of EPO after different treatments was determined by histological examination, immunohistochemistry and in situ hybridization. Results The mRNA and protein expressions of EPO could be detected in survival and necrotic neurons, glia as well as vascular endothelial cells. Focal cerebral ischemia promoted the expression of EPO. Significant enhanced EPO level was found in the ischemic peripheral zone after acupuncture preconditioning (P < 0.05). Conclusion Our results demonstrated that acupuncture preconditioning enhanced the expression of EPO in neurons, glia and vascular endothelial cells the ischemic peripheral zone, suggesting the involvement of EPO in acupuncture preconditioning-induced neuroprotection following focal cerebral ischemia. EPO may exert neuroprotective effects through promoting neurotrophic support and angiogenesis.

scholarly journals Neuroprotective Effects of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells in Transient Focal Cerebral Ischemia in Rats

2009 ◽  
Vol 29 (4) ◽  
pp. 780-791 ◽  
Author(s):  
Yi-Ping Liu ◽  
Hakan Seçkin ◽  
Yusuf İzci ◽  
Zhong Wei Du ◽  
Yi-Ping Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Embryonic Stem Cells ◽  
Cerebral Ischemia ◽  
Human Embryonic Stem Cells ◽  
Focal Cerebral Ischemia ◽  
Embryonic Stem ◽  
Transient Focal Cerebral Ischemia ◽  
Infarction Volume

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for β-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.

scholarly journals Tolerogenic Properties of Lymphatic Endothelial Cells Are Controlled by the Lymph Node Microenvironment

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e87740 ◽  
Author(s):  
Jarish N. Cohen ◽  
Eric F. Tewalt ◽  
Sherin J. Rouhani ◽  
Erica L. Buonomo ◽  
Amber N. Bruce ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymphatic Endothelial Cells

scholarly journals Sustained Blockade of Brain AT1 Receptors before and after Focal Cerebral Ischemia Alleviates Neurologic Deficits and Reduces Neuronal Injury, Apoptosis, and Inflammatory Responses in the Rat

2004 ◽  
Vol 24 (5) ◽  
pp. 536-547 ◽  
Author(s):  
Min Lou ◽  
Annegret Blume ◽  
Yi Zhao ◽  
Peter Gohlke ◽  
Günther Deuschl ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Inflammatory Responses ◽  
Focal Cerebral Ischemia ◽  
At1 Receptor ◽  
Neuroprotective Effects ◽  
Reactive Microglia ◽  
At1 Receptors ◽  
Before And After

In the present study, we investigate whether a long-term blockade of brain AT1 receptors in male Wistar rats before and after ischemic injury exerts neuroprotective effects and modulates apoptosis and inflammatory responses, which are associated with the post-ischemic progression of brain damage. The AT1 receptor antagonist irbesartan was continuously infused intracerebroventricularly using osmotic minipumps over a 5-day period before and for 3 or 7 days after middle cerebral artery occlusion (MCAO) for 90 minutes. Neurologic status was evaluated daily, starting 24 hours after MCAO. After MCAO (3 and 7 days), brains were removed for the measurement of infarct size and immunohistochemical evaluation of apoptosis and accumulation of reactive microglia and macrophages. Treatment with irbesartan before ischemia improved motor functions, whereas post-ischemic treatment improved sensory functions. Blockade of brain AT1 receptors reduced the infarct size on days 3 and 7 after MCAO. In the peri-infarct cortex, irbesartan treatment decreased the number of apoptotic cells on day 3 and attenuated the invasion of activated microglia and macrophages on days 3 and 7 after ischemia. Long-term blockade of brain AT1 receptors improves the recovery from cerebral ischemia. Antiapoptotic mechanisms and inhibition of post-ischemic inflammation are involved in the AT1 receptor blockade-induced neuroprotective effects in ischemic brain tissue.

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