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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu michael chopp michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Exosome treatment for stroke with diabetic comorbidity

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Neural Regeneration Research 2022年第2期17卷 315-317页

作者： Poornima Venkat michael chopp Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Ischemic stroke is a cerebrovasculardisease with a high risk of mortality andlong-lasting neurological *** advances have resulted in adeclining trend in stroke incidence anddeaths in the United States. However,increas... 详细信息

关键词： mortality morbidity Exosome

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Multifaceted roles of pericytesinterorgan interactions

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Neural Regeneration Research 2021年第5期16卷 982-983页

作者： Zhitong Zheng michael chopp Jieli Chen Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Microvascular dysfunction has been implicated in many diseases such as stroke and *** addition to the microvascular endothelial cell(EC),the pericyte,a perivascular cell that adheres to the abluminal side of the EC may also be important to ensure proper microvascular *** a prominent perivascular cell,the pericyte has garnered increasing attention for its multiple functional aspects,especially the pericyte of central nervous system(Yemisci et al.,2009;Armulik et al.,2010;Gaceb et al.,2018).

关键词： al. pericyte function.

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Axonal remodeling of the corticospinal tract during neurological recovery after stroke

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Neural Regeneration Research 2021年第5期16卷 939-943页

作者： Zhongwu Liu Hongqi Xin michael chopp Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Stroke remains the leading cause of long-term *** is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor *** the only direct descending motor pathway,the corticospinal tract(CST)is the primary pathway to innervate spinal motor neurons,and thus,forms the neuroanatomical basis to control the peripheral muscles for voluntary ***,we review evidence from both experimental animals and stroke patients,regarding CST axonal damage,functional contribution of CST axonal integrity and remodeling to neurological recovery,and therapeutic approaches aimed to enhance CST axonal remodeling after *** new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation,which will significantly impact the current clinical needs of subacute and chronic stroke treatment.

关键词： axonal degeneration axonal integrity axonal remodeling corticospinal tract motor performance neurological recovery stroke therapeutic strategy

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Experimental animal models and infl ammatory cellular changes in cerebral ischemic and hemorrhagic stroke

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Neuroscience Bulletin 2015年第6期31卷 717-734页

作者： Tao Yan michael chopp Jieli Chen Tianjin Neurological Institute Department of NeurologyTianjin Medical University General Hospital Department of Neurology Henry Ford Hospital Department of Physics Oakland University Department of Gerontology Tianjin Gerontology InstituteTianjin Medical University General Hospital

Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans.

关键词： ischemic stroke hemorrhagic stroke animal model inflammatory cells

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Reactive astrocytes promote axonal remodeling and neurological recovery after stroke

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Neural Regeneration Research 2014年第21期9卷 1874-1875页

作者： Zhongwu Liu Hongqi Xin michael chopp Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Stroke is a leading cause of death and disability in adults worldwide. For decades, the primary approach and goal of therapy for stroke has focused on neuroprotection, namely treating the injured tissue, with interventions designed to reduce the volume of cerebral infarction. Enormous effort in the laboratory has been devoted to the development of neuroprotective agents in an attempt to salvage ischemic neurons in the brain from irreversible injury; however, all these efforts have failed to demonstrate efficacy in clinical trials of stroke. In order to treat stroke, we have to re-con- ceptualize and redefine our therapeutic targets. Acute neu- roprotective treatments for stroke fight a temporal battle of salvaging cerebral tissue before the onset of death, as well as a physiological impediment of delivery of therapy to tissue which has inadequate blood flow.

关键词： GFAP CSPG Reactive astrocytes promote axonal remodeling and neurological recovery after stroke

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Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration

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Neural Regeneration Research 2024年第1期19卷 49-54页

作者： Ye Xiong Asim Mahmood michael chopp Department of Neurosurgery Henry Ford HospitalDetroitMIUSA Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Traumatic brain injury is a serious and complex neurological condition that affects millions of people *** significant advancements in the field of medicine,effective treatments for traumatic brain injury remain ***,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain *** vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and *** administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional *** preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor *** further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain *** this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.

关键词： biomarkers extracellular vesicles functional outcome mesenchymal stem/stromal cells neuroinflammation neuroplasticity neuroprotection traumatic brain injury

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Remodeling dendritic spines for treatment of traumatic brain injury

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Neural Regeneration Research 2019年第9期14卷 1477-1480页

Traumatic brain injury is an important global public health *** brain injury not only causes neural cell death,but also induces dendritic spine *** neurons from cell death in the injured brain may exhibit dendrite damage,dendritic spine degeneration,mature spine loss,synapse loss,and impairment of *** degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain *** function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target *** synaptic plasticity,the numbers and shapes of dendritic spines undergo dynamic *** of spine heads and the formation and stabilization of new spines are associated with long-term potentiation,while spine shrinkage and retraction are associated with long-term *** of memory is associated with remodeling and growth of preexisting synapses and the formation of new *** date,there is no effective treatment to prevent dendritic degeneration and synapse *** review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain *** mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive,possibly including blocking activation of Cofilin induced by beta amyloid,Ras activation,and inhibition of GSK-3 signaling *** understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.

关键词： traumatic brain injury dendritic spines synaptic plasticity spinogenic agents treatment spine remodeling memory functional recovery

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Emerging potential of exosomes for treatment of traumatic brain injury

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Neural Regeneration Research 2017年第1期12卷 19-22页

Traumatic brain injury（TBI） is one of the major causes of death and disability *** effective treatment has been identified from clinical *** evidence exists that treatment with mesenchymal stem cells（MSCs） exerts a substantial therapeutic effect after experimental brain *** addition to their soluble factors,therapeutic effects of MSCs may be attributed to their generation and release of *** are endosomal origin small-membrane nano-sized vesicles generated by almost all cell *** play a pivotal role in intercellular *** delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after *** effects of exosomes derive from the exosome content,especially micro RNAs（mi RNAs）.mi RNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of *** with their parent cells,exosomes are more stable and can cross the blood-brain *** have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted *** a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery,potentially for a variety of neural injuries and neurodegenerative *** review discusses the most recent knowledge of exosome therapies for TBI,their associated challenges and opportunities.

关键词： traumatic brain injury exosomes microRNAs mesenchymal stem cells treatment neuroplasticity cell therapy

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PDE5 inhibitors promote recovery of peripheral neuropathy in diabetic mice

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Neural Regeneration Research 2017年第2期12卷 218-219页

作者： Lei Wang michael chopp Zheng Gang Zhang Department of Neurology Henry Ford Hospital Detroit MI USA Department of Physics Oakland University Rochester MI USA

Diabetes mellitus affects an estimated 422 million people *** neuropathy is one of the most common and disabling complications of *** is currently no effective treatment for diabetic neuropathy,

关键词： PDE5 inhibitors promote recovery of peripheral neuropathy in diabetic mice

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