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Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

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Neural Regeneration Research 2024年第3期19卷 671-679页

作者： Chunyun Liu Shangde Guo Rong Liu Minfang Guo Qing Wang Zhi Chai Baoguo Xiao Cungen Ma Institute of brain Science Shanxi Datong UniversityDatongShanxi ProvinceChina The Key Research Laboratory of Benefiting Qi for Acting blood Cireulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology Shanxi University of Chinese MedicineTaiyuanShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous *** polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple *** study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune *** found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and ***,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified *** addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced *** findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for m

关键词： anti-inflammatory experimental autoimmune encephalomyelitis Fasudil macrophage multiple sclerosis pro-inflammatory Rho kinase

Characteristic Features of Deep brain Lymphatic vessels and Their Regulation by Chronic Stress

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Research 2023年第4期2023卷 657-670页

作者： Junzhuang Chang Bingqing Guo Yan Gao Wei Li Xiaoyu Tong Yi Feng Nashat Abumaria State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for brain Science Institutes of Brain ScienceFudan UniversityShanghai 200032China Department of Integrative Medicine and Neurobiology School of Basic Medical SciencesInstitutes of Brain ScienceBrain Science Collaborative Innovation CenterState Key Laboratory of Medical NeurobiologyInstitute of Acupuncture and MoxibustionFudan Institutes of Integrative MedicineFudan UniversityShanghai 200032China

Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the ***,it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life *** used tissue clearing techniques,immunostaining,light-sheet whole-brain imaging,confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain *** unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful *** blotting and coimmunoprecipitation were used to provide mechanistic *** demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex,cerebellum,hippocampus,midbrain,and ***,we showed that deep brain lymphatic vessels can be regulated by stressful life *** stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the *** changes were observed in prefrontal cortex,lateral habenula,or dorsal raphe *** corticosterone treatment reduced lymphatic endothelial cell markers in the ***,chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization *** results provide new insights into the characteristic features of deep brain lymphatic vessels,as well as their regulation by stressful life events.

关键词： insight stress Deep

Role of three-dimensional imaging integration in atrial fibrillation ablation

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World Journal of Cardiology 2010年第8期2卷 215-222页

作者： Roberto De Ponti Raffaella Marazzi Domenico Lumia Giuseppe Picciolo Roberto Biddau Carlo Fugazzola Jorge A Salerno-Uriarte Department of Heart Brain and VesselsOspedale di Circolo e Fondazione MacchiUniversity of Insubria Department of Radiology Ospedale di Circolo e Fondazione MacchiUniversity of Insubria

Atrial fibrillation is the most common arrhythmia and in symptomatic patients with a drug-refractory form,catheter ablation aimed at electrically disconnecting the pulmonary veins(PVs) has proved more effective than use of antiarrhythmic drugs in maintaining sinus rhythm during *** the other hand,this ablation procedure is complex,requires specific training and adequate clinical experience.A main challenge is represented by the need for accurate sequential positioning of the ablation catheter around each veno-atrial junction to deliver point-by-point radiofrequency energy applications in order to achieve complete and persistent electrical disconnection of the *** integration is a new technology that enables guidance during this procedure by showing a three-dimensional,pre-acquired computed tomography or magnetic resonance image and the relative real-time position of the ablation catheter on the screen of the electroanatomic *** in the literature suggest that imaging integration provides accurate visual information with improvement in the procedure parameters and/or clinical outcomes of the procedure.

关键词： Catheter ablation Atrial fibrillation Electroanatomic mapping Multislice computed tomography Magnetic resonance imaging

Angiogenesis and neuronal remodeling after ischemic stroke

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Neural Regeneration Research 2020年第1期15卷 16-19页

作者： Masahiro Hatakeyama Itaru Ninomiya Masato Kanazawa Department of Neurology Brain Research Institute Niigata University

Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal *** raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic *** vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a *** this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral *** occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and ***-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional ***,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin ***,blood vessels are thought to enhance neurogenesis in three stages:1)blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature ***,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.

关键词： angiogenesis axonal outgrowth cerebral ischemia coupling functional recovery guidance neurogenesis stroke

Microglia Suppresses Breast Cancer brain Metastasis via a Pro-inflammatory Response

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Neuroscience Bulletin 2024年第7期40卷 1034-1036页

作者： Shengbo Chen Yi-Jun Liu Department of Neurobiology of Affiliated Mental Health Center and Hangzhou Seventh People's Hospital and School of brain Science and brain Medicine Zhejiang University School of MedicineHangzhou 310058China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-machine IntelligenceZhejiang University1369 West Wenyi RoadHangzhou 311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou 310058China

Due to the obstacle of the blood-brain barrier(BBB)for drug delivery[1],breast cancer brain metastasis(BCBM)represents a worldwide health challenge with high *** BCBM formation and progression,brain metastases(BrMs)secret various factors,including cytokines and exosomes,and trigger the infiltration of tumours-associated macrophages(TAMs),which in turn become important components of brain tumour microenvironments(TME).

关键词： mortality tumour Breast

Fast-tracking regenerative medicine for traumatic brain injury

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Neural Regeneration Research 2020年第7期15卷 1179-1190页

作者： Brooke Bonsack Matt Heyck Chase Kingsbury Blaise Cozene Nadia Sadanandan Jea-Young Lee Cesar V. Borlongan Center of Excellence for Aging and brain Repair University of South Florida College of Medicine

Traumatic brain injury remains a global health crisis that spans all demographics,yet there exist limited treatment options that may effectively curtail its lingering *** brain injury pathology entails a progression from primary injury to inflammation-mediated secondary cell *** this inflammation as a means of ameliorating the greater symptomology of traumatic brain injury has emerged as an attractive treatment *** this review,we recapitulate and evaluate the important developments relating to regulating traumatic brain injury-induced neuroinflammation,edema,and blood-brain barrier disintegration through pharmacotherapy and stem cell *** these studies of stand-alone treatments have yielded some positive results,more therapeutic outcomes have been documented from the promising area of combined drug and stem cell *** the facilitatory properties of certain pharmaceuticals with the anti-inflammatory and regenerative effects of stem cell transplants creates a synergistic effect greater than the sum of its *** burgeoning evidence in favor of combined drug and stem cell therapies warrants more elaborate preclinical studies on this topic in order to pave the way for later clinical trials.

关键词： clinical trials combined therapy inflammatory cascade neuroinflammation neuroprotection neurotrauma pharmacotherapy preclinical studies secondary cell death stem cells

Breakthrough in Structural and Functional Dissection of the Hypothalamo-Neurohypophysial System

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Neuroscience Bulletin 2021年第7期37卷 1087-1089页

作者： Ying Wang Huamin Xu Xia Zhang Institute of brain Science and Disease Qingdao UniversityQingdao 266071China

The projections from hypothalamic magnocellular neuroendocrine cells(MNCs)to the posterior pituitary(PPi)are traditionally defined as the hypothalamo-neurohy-pophysial system(HNS),which releases oxytocin(OXT)and arginine vasopressin(AVP)into the blood stream to regulate peripheral function[1].Recently,accumulating evidence has confirmed that OXT and AVP are not only involved in peripheral regulation[2],but also contribute to various central actions[3,4],such as memory and social and stress-related behaviors[5].However,peripherally released OXT and AVP rarely cross the blood-brain barrier and return to the central nervous ***,whether and how they exert central effects remain to be *** is supposed that MNCs projecting to the PPi also have collaterals projecting centrally,and these might be responsible for the central actions of OXT and *** there has been no cell-type-specific dissection of the hypothalamic MNC projections,due to the limited methods and techniques for imaging and manipulation.

关键词： manipulation return traditionally

Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inflammation following traumatic brain injury

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Neural Regeneration Research 2016年第9期11卷 1379-1384页

作者： Sherwin Mashkouri Marci G.Crowley Michael G.Liska Sydney Corey Cesar V.Borlongan Department of Neurosurgery and brain Repair University of South Florida Morsani College of Medicine

The pathologic process of chronic phase traumatic brain injury is associated with spreading inflamma- tion, cell death, and neural dysfunction. It is thought that sequestration of inflammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration. Studies have targeted post-traumatic brain injury inflammation with the use of pharmacotherapy and cell therapy. These thera- peutic options are aimed at reducing the edematous and neurodegenerative inflammation that have been associated with compromising the integrity of the blood-brain barrier. Although studies have yielded posi- tive results from anti-inflammatory pharmacotherapy and cell therapy individually, emerging research has begun to target inflammation using combination therapy. The joint use of anti-inflammatory drugs along- side stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients. Despite the promising results in this field of research, it is important to note that most of the studies men- tioned in this review have completed their studies using animal models. Translation of this research into a clinical setting will require additional laboratory experiments and larger predinical trials.

关键词： stem cells drugs neuroinflammation trauma neuroprotection regeneration

Next-generation regenerative therapy for ischemic stroke using peripheral blood mononuclear cells

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Neural Regeneration Research 2024年第11期19卷 2341-2342页

作者： Masato Kanazawa Itaru Ninomiya Yutaka Otsu Masahiro Hatakeyama Department of Neurology Brain Research InstituteNiigata UniversityNiigataJapan

Stroke is the second leading cause of death and the third leading cause of disability worldwide after heart *** predict that stroke deaths and permanent disabilities will increase worldwide by the year ***-target therapies may be insufficient,because ischemic cerebral injury involves several ***-mediated therapies are ideal,because they target multiple cell types to enhance protection and recovery.

关键词： ischemic death cerebral