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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Neural Regeneration research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids research institute Neuroscience and Mental Health ProgramTorontoONCanada institute of Biomaterials and biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

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Neural Regeneration research 2025年第11期20卷 3213-3214页

作者： Sheharyar S.Baig Ali N.Ali Arshad Majid Sheffield institute for translational Neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

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Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural Regeneration research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish research institute of translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

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Making bridges between preclinical and clinical insights into age-related cognitive decline

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Neural Regeneration research 2025年第8期20卷 2321-2322页

作者： David VC Brito Clévio Nóbrega Algarve biomedical Center-research institute(ABC-RI) Campus GambelasFaroPortugal Algarve biomedical Center-(ABC) Campus GambelasFaroPortugal Faculty of Medicine and biomedical Sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether th... 详细信息

关键词： bridges becoming insight

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Glia-to-neuron reprogramming to the rescue?

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Neural Regeneration research 2025年第5期20卷 1395-1396页

作者： Jack W.Hickmott Cindi M.Morshead Department of Surgery University of TorontoTorontoONCanada Donnelly Centre for Cellular and Biomolecular research TorontoONCanada institute of biomedical Engineering University of TorontoTorontoONCanada The KITE research institute Toronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative *** brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be *** exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

关键词： programming passing proof

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Proteostasis failure:at the intersection between aging and Alzheimer's disease

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Neural Regeneration research 2025年第11期20卷 3221-3222页

作者： Natalia Poblete Claudio Hetz Center for Geroscience Brain Health and MetabolismSantiagoChile biomedical Neuroscience institute Faculty of MedicineUniversity of ChileSantiagoChile Program of Cellular and Molecular Biology Institute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile Buck institute for research on Aging NovatoCAUSA

Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of *** we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to *** is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloid β and hyper-phosphorylated,Tau in addition to neuroinflammation.

关键词： Alzheimer amyloid stasis

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Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration research 2025年第2期20卷 481-482页

作者： Khaled Alok Timothy G.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA translational Brain research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

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Insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An M.Voets Tim Vanmierlo Rudy Schreiber BIOMED biomedical research institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium Department of Psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands University MS Center(UMSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

关键词： academic approval consequences

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and Clinical research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina institute of Neuroscience&Jiangsu Key Laboratory of translational research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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