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Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling

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Author:: No author available

Journal Title:: Neural Regeneration Research

Issue:: 6

DOI:: No doi available

Key Word:: apoptosis;axonal regeneration;c-Jun;exosomes;functional remodeling;ischemic stroke;JNK1;mesenchymal stem cells;synaptic formation;treadmill exercise

Abstract： Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

Reference

[1]Charlotte Zerna,G?tz Thomalla,Bruce C V Campbell,etc.Current practice and future directions in the diagnosis and acute treatment of ischaemic stroke[J].2018,392(10154).
[2]Puig, Berta,Brenna, Santra,Magnus, Tim.Molecular Communication of a Dying Neuron in Stroke[J].2018,19(9).
[3]Shi, Bo,Ding, Jianxun,Liu, Yi,etc.ERK1/2 Pathway-Mediated Differentiation of IGF-1-Transfected Spinal Cord-Derived Neural Stem Cells into Oligodendrocytes.[J].2014,9(8).
[4]Hacke W,Kaste M,Bluhmki E,etc.Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.[J].2008,359(13).
[5]Yuhui, Hu,Qin, Zhan,Haibo, Zhang,etc.Increased Susceptibility to Ischemic Brain Injury in Neuroplastin 65-Deficient Mice Likely via Glutamate Excitotoxicity.[J].2017,11(Spec ).
[6]Xiao, Zhong-Dang,Tian, Tian,Gao, Jun,etc.Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy[J].2018,150.
[7]Jieli Chen,Zheng Zhang,Yi Li,etc.Intravenous Administration of Human Bone Marrow Stromal Cells Induces Angiogenesis in the Ischemic Boundary Zone After Stroke in Rats[J].2003,92(6).
[8]Schneider, C.A.,Rasband, W.S.,Eliceiri, K.W..NIH Image to ImageJ: 25 years of image analysis[J].2012,9(7).
[9]Quan-guang, Zhang,Dong, Han,Rui-min, Wang,etc.C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-alpha and the critical period hypothesis of estrogen neuroprotection.[J].2011,108(35).
[10]Xin,H.,Katakowski,M.,Wang,X.,etc.Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth[J].2012,30(7).
[11]Yongxing,Lai,Peiqiang,Lin,Manli,Chen,etc.Restoration of L-OPA1 alleviates acute ischemic stroke injury in rats via inhibiting neuronal apoptosis and preserving mitochondrial function.[J].2020.
[12]Shan-Shan,Meng,Xiu-Ping,Xu,Wei,Chang,etc.LincRNA-p21 promotes mesenchymal stem cell migration capacity and survival through hypoxic preconditioning.[J].2018,9(1).
[13]Sarmah, Deepaneeta,Kaur, Harpreet,Saraf, Jackson,etc.Getting Closer to an Effective Intervention of Ischemic Stroke: The Big Promise of Stem Cell[J].2018,9(4).
[14]Eleanor T Coffey.Nuclear and cytosolic JNK signalling in neurons.[J].2014,15(5).
[15]Enrique Longa,Philip Weinstein,Sara Carlson,etc.Reversible Middle Cerebral Artery Occlusion Without Craniectomy in Rats[J].1989,20(1).
[16].JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships[J].2016,80(3).
[17]Li-cai Yang,Quan-Guang Zhang,Cai-feng Zhou,etc.Extranuclear Estrogen Receptors Mediate the Neuroprotective Effects of Estrogen in the Rat Hippocampus.[J].2010,5(5).
[18]Sun, Hao,Li, Ao,Hou, Tingting,etc.Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats[J].2019,82.
[19]Hofmeijer J,van Putten MJ.Ischemic cerebral damage: an appraisal of synaptic failure.[J].2012,43(2).
[20]Michael, Chopp,Yi, Li.Treatment of neural injury with marrow stromal cells.[J].2002,1(2).
[21]Richard J, Lobb,Melanie, Becker,Shu Wen, Wen,etc.Optimized exosome isolation protocol for cell culture supernatant and human plasma.[J].2015,4.
[22]Yi-Xian, Zhang,Ming-Zhou, Yuan,Lin, Cheng,etc.Treadmill exercise enhances therapeutic potency of transplanted bone mesenchymal stem cells in cerebral ischemic rats via anti-apoptotic effects.[J].2015,16.
[23]Winstein, Carolee J.,Stein, Joel,Arena, Ross,etc.Guidelines for Adult Stroke Rehabilitation and Recovery A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association[J].2016,47(6).
[24]Mouwei, Zheng,Ronghua, Chen,Hongbin, Chen,etc.Netrin-1 Promotes Synaptic Formation and Axonal Regeneration via JNK1/c-Jun Pathway after the Middle Cerebral Artery Occlusion.[J].2018,12(Spec ).
[25]Xie, Qingfeng,Cheng, Jingyan,Pan, Guoyuan,etc.Treadmill exercise ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting dendritic modification and synaptic plasticity via upregulating caveolin-1/VEGF signaling pathways[J].2019,313.
[26]Yinuo,Lin,Chi,Zhang,Pingping,Xiang,etc.Exosomes derived from HeLa cells break down vascular integrity by triggering endoplasmic reticulum stress in endothelial cells.[J].2020,9(1).
[27]Oh Young,Bang,Eun Hee,Kim.Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Stroke: Challenges and Progress.[J].2019,10.
[28]Sommer, Clemens J..Ischemic stroke: experimental models and reality[J].2017,133(2).
[29]Seo,J.H.,Terasaki,Y.,Arai,K.,etc.Delayed inhibition of c-Jun N-Terminal kinase worsens outcomes after focal cerebral ischemia[J].2012,32(24).
[30]Xin,H.,Li,Y.,Cui,Y.,etc.Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats[J].2013,33(11).
[31]X. WANG,M. ZHANG,S.-D. YANG,etc.Pre-Ischemic Treadmill Training Alleviates Brain Damage via Glt-1-Mediated Signal Pathway after Ischemic Stroke in Rats[J].2014,274.
[32]Masoud Soleimani,Samad Nadri.A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow[J].2009,4(1).
[33]Nateri AS,Da Costa C,Wagner EF,etc.The AP-1 transcription factor c-Jun is required for efficient axonal regeneration.[J].2004,43(1).
[34]Flavell RA,Kuan CY,Davis RJ,etc.The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development.[J].1999,22(4).
[35].C-Jun N-terminal kinase 1 (JNK1) is required for coordination of netrin signaling in axon guidance[J].2013,288(3).
[36]Gittler, Michelle,Davis, Andrew M..Guidelines for Adult Stroke Rehabilitation and Recovery[J].2018,319(8).
[37]Tollar, Jozsef,Nagy, Ferenc,Csutoras, Bence,etc.High Frequency and Intensity Rehabilitation in 641 Subacute Ischemic Stroke Patients[J].2021,102(1).
[38]Du H,Chen R,Huang H,etc.Effects of treadmill exercise on the expression of netrin-1 and its receptors in rat brain after cerebral ischemia.[J].2011,194.
[39]van Niel, Guillaume,D'Angelo, Gisela,Raposo, Graca.Shedding light on the cell biology of extracellular vesicles[J].2018,19(4).
[40]Pengyue Zhang,Yuling Zhang,Jie Zhang,etc.Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats.[J].2013,14(3).
[41]Barthels, Derek,Das, Hiranmoy.Current advances in ischemic stroke research and therapies[J].2020,1866(4).
[42]Xin, Hongqi,Katakowski, Mark,Wang, Fengjie,etc.MicroRNA cluster miR-17-92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats[J].2017,48(3).
[43]Ratajczak J,Wysoczynski M,Hayek F,etc.Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication[J].2006,20(9).
[44]Xanthi, Antoniou,Tiziana, Borsello.The JNK signalling transduction pathway in the brain.[J].2012,4.
[45]Cheng Wang,Jessica Redgrave,Mohsen Shafizadeh,etc.Aerobic exercise interventions reduce blood pressure in patients after stroke or transient ischaemic attack: a systematic review and meta-analysis[J].2019,53(24).
[46]Lufen Chang,Ying Jones,Mark H. Ellisman,etc.JNK1 Is Required for maintenance of neuronal Microtubules and Controls Phosphorylation of Microtubule-Associated Proteins[J].2003,4(4).
[47]Venkat, Poornima,Zacharek, Alex,Landschoot-Ward, Julie,etc.Exosomes derived from bone marrow mesenchymal stem cells harvested from type two diabetes rats promotes neurorestorative effects after stroke in type two diabetes rats[J].2020,334.
[48]Honmou,O.,Sasaki,M.,Kocsis,J.D.,etc.Mesenchymal stem cells: Therapeutic outlook for stroke[J].2012,18(5).
[49]Lu M,Zhang Z,Lu D,etc.Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats.[J].2001,32(4).
[50]Lorenzo,Muzzi,Gerco,Hassink,Marloes,Levers,etc.Mild stimulation improves neuronal survival in an in-vitro model of the ischemic penumbra.[J].2019.