Neurotherapeutics最新文献

{"title":"The ExTINGUISH modified Rankin Scale: A Comprehensive Functional Outcome Measure for NMDAR Encephalitis","authors":"Ka-Ho Wong, Gregory Day, Christopher Coffey, Ursula Utz, David Clifford, Eric Klawiter, J Robinson Singleton, Dixie Ecklund, David Klements, Michele Costigan, Erin Steinhart, Brenda Pearson, Christina Desir, Josep Dalmau, Maarten Titulaer, Stacey Clardy","doi":"10.1016/j.neurot.2026.e00981","DOIUrl":"10.1016/j.neurot.2026.e00981","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e00981"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NeuroNEXT Gene Therapy Consortium – Contributions to Gene-Based Therapies in Ultra-Rare Neurological Disorders","authors":"David Klements MS, Marianne Chase, Aleksander Videnovic MD, Christopher Coffey PhD, Dixie Ecklund RN, MSN, MBA, Joan Ohayon RN, MSN, CRNP, MSCN, Lumy Sawaki-Adams MD, PhD, Merit Cudkowicz MD, MSC","doi":"10.1016/j.neurot.2026.e00990","DOIUrl":"10.1016/j.neurot.2026.e00990","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e00990"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc as a phase-specific therapeutic target in hypoglycemia-induced brain injury","authors":"Dong Gyun Ko,&nbsp;Hyun Wook Yang,&nbsp;Hyun Ho Jeong,&nbsp;Min Kyu Park,&nbsp;Bo Young Choi,&nbsp;Seok Joon Won,&nbsp;Raymond A. Swanson,&nbsp;Sang Won Suh","doi":"10.1016/j.neurot.2026.e00962","DOIUrl":"10.1016/j.neurot.2026.e00962","url":null,"abstract":"<div><div>Hypoglycemia remains a major cause of neurological morbidity. However, effective targeted therapies for affected brain regions remain lacking. Although excitotoxicity and energy failure have long been implicated, emerging evidence has identified dysregulated zinc signaling as a central mediator of neuronal vulnerability and recovery. During acute glucose deprivation, synapse-released zinc accumulates intracellularly, impairing mitochondrial function, activating nicotinamide adenine dinucleotide phosphate oxidase, amplifying oxidative stress, and triggering poly (ADP-ribose) polymerase-dependent cell death pathways. Notably, neuronal injury is markedly exacerbated during glucose reperfusion, when zinc–reactive oxygen species coupling drives metabolic collapse. During the recovery phase, zinc contributes to neurogenesis, synaptic remodeling, and circuit repair, underscoring its phase-dependent duality. Here, we synthesize mechanistic and translational evidence supporting zinc as a dynamic regulator of neuronal fate in hypoglycemia-induced brain injury. We propose that zinc functions as a metabolic switch linking acute oxidative injury to subsequent regenerative processes. Importantly, this framework suggests a precision-timed therapeutic strategy involving acute zinc chelation or inhibition of zinc-coupled oxidative pathways during injury, followed by controlled restoration of zinc-dependent signaling during recovery. By redefining hypoglycemic brain injury through phase-specific zinc modulation, we identify new therapeutic opportunities relevant not only to hypoglycemia but also to broader metabolic and ischemic brain disorders.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e00962"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights on the cellular mechanisms of intracranial electrical stimulation using optical imaging in preclinical models","authors":"Cara Ravasio,&nbsp;Mohammed Abumuaileq,&nbsp;Mohigul Nasimova,&nbsp;Jiancheng Xie,&nbsp;Dana C. Shaw,&nbsp;Audrey Lindsay,&nbsp;Catherine J. Chu,&nbsp;Xue Han","doi":"10.1016/j.neurot.2026.e01043","DOIUrl":"10.1016/j.neurot.2026.e01043","url":null,"abstract":"<div><div>Intracranial electrical stimulation is increasingly used to treat neurological and psychiatric conditions. However, the underlying therapeutic mechanisms at the cellular and circuit levels remain poorly understood. Exciting progress in the development of genetically encoded neural activity indicators enables artifact-free, high-spatiotemporal-resolution optical analysis of the impact of intracranial stimulation on membrane potentials, cytosolic calcium, and neurotransmitter and neuromodulator dynamics. Using these optical imaging tools <em>in vivo</em>, in the mammalian brain, preclinical studies probed the effect of intracranial stimulation on individual neurons and population network dynamics across timescales ranging from milliseconds to minutes or more. These studies have revealed complex, stimulation parameter-dependent effects across cell types and provided experimental support for various therapeutic mechanisms. We discuss these studies in the context of clinical observations and highlight the exciting potential of optical imaging in advancing the mechanistic understanding of clinical electrical stimulation in epilepsy and other neurological and psychiatric orders.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01043"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and adverse event profiles in neuromodulation therapies for drug-resistant epilepsy","authors":"Yuta Tanoue,&nbsp;Masaki Izumi,&nbsp;Samuel S. Ahn,&nbsp;Dawn S. Eliashiv,&nbsp;Jerome Engel Jr.,&nbsp;Ausaf A. Bari,&nbsp;Itzhak Fried,&nbsp;Aria Fallah,&nbsp;Hiroki Nariai","doi":"10.1016/j.neurot.2026.e01042","DOIUrl":"10.1016/j.neurot.2026.e01042","url":null,"abstract":"<div><div>Drug-resistant epilepsy (DRE) is associated with clinical and psychosocial burdens, and non-pharmacological therapies play an important role when seizure control cannot be achieved with antiseizure medications alone. Neuromodulation therapies, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), have become important options for patients who are not suitable candidates for resective or disconnective surgery. Although these modalities have demonstrated efficacy for seizure reduction, they differ in surgical invasiveness, stimulation targets, device structures, programming strategies, and long-term management requirements. These differences result in distinct adverse event (AE) profiles for treatment selection. In this review, we summarize AEs and long-term management considerations associated with VNS, DBS, and RNS and classify them into four categories: procedure-related AEs, stimulation-related AEs including neuropsychiatric and cognitive issues, device-related AEs, and long-term management considerations. VNS avoids intracranial surgery but is associated with stimulation-related laryngopharyngeal symptoms and generator and wire management. DBS allows direct modulation of deep brain networks but carries risks of intracranial lead implantation, targeting accuracy, and psychiatric or cognitive effects. RNS provides closed-loop stimulation and chronic intracranial electroencephalographic recording, but requires implantation of intracranial leads and a cranially implanted neurostimulator, localization of the epileptogenic network, and specialized long-term data review, programming, and device management. Across all three modalities, device-related infection, battery depletion or replacement, and ongoing device management are common safety concerns. Understanding these modality-specific AE profiles may help clinicians select candidates, counsel patients and families, and develop safe and sustainable long-term treatment strategies for DRE.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01042"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148770286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A head-to-head assessment of VMAT2 target occupancy of once-daily valbenazine compared to deutetrabenazine extended release","authors":"Daniel Albrecht,&nbsp;Satjit Brar,&nbsp;Wei Hou,&nbsp;Hui Zhang,&nbsp;Gena Riggs,&nbsp;Shannon Ingersoll,&nbsp;Jessica Maynard-Scott,&nbsp;Ryan Terry-Lorenzo,&nbsp;Ava Nguyen,&nbsp;Zeynep Demir,&nbsp;Christine Sandiego,&nbsp;Cristian Constantinescu,&nbsp;Eugenii A. Rabiner,&nbsp;David S. Russell,&nbsp;Dietrich Haubenberger","doi":"10.1016/j.neurot.2026.e01024","DOIUrl":"10.1016/j.neurot.2026.e01024","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01024"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective potentiation of NaV1.1 channels by Small Molecule XPC-A in Dravet mice suppresses spontaneous seizures, prevents SUDEP, and increases Long Term Potentiation","authors":"Samuel Goodchild PhD,&nbsp;Kristen Burford PhD,&nbsp;Celine Dube PhD,&nbsp;Samrat Thouta PhD,&nbsp;Arjun Mahadevan PhD,&nbsp;Matt Waldbrook,&nbsp;Maegan Soriano,&nbsp;Maja Filipovic,&nbsp;Vishaal Rajani PhD,&nbsp;Emily Hurley PhD,&nbsp;Sarah Bryan,&nbsp;Verner Lofstrand PhD,&nbsp;Helen Clement PhD,&nbsp;Davie Kim,&nbsp;Steven Wesolowski,&nbsp;Alison Cutts PhD,&nbsp;James Empfield PhD,&nbsp;J.P. Johnson PhD","doi":"10.1016/j.neurot.2026.e01015","DOIUrl":"10.1016/j.neurot.2026.e01015","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01015"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Neural Stem Cell Fate by Reactive Glial Cells","authors":"Ashley Hein","doi":"10.1016/j.neurot.2026.e01004","DOIUrl":"10.1016/j.neurot.2026.e01004","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01004"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the Secondary Response to Traumatic Brain Injury Using Spatial Transcriptomics Shows Acute 4-aminopyridine Treatment Mitigates Axonal and Molecular Pathology","authors":"Genevieve M. Sullivan,&nbsp;Kryslaine L. Radomski,&nbsp;Shaoqiu He,&nbsp;Matthew D. Wilkerson,&nbsp;Clifton L. Dalgard,&nbsp;Camille Alba,&nbsp;Xiaomei Zi,&nbsp;Martin L. Doughty,&nbsp;Regina Armstrong","doi":"10.1016/j.neurot.2026.e01002","DOIUrl":"10.1016/j.neurot.2026.e01002","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01002"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease-modifying effects of 4-aminopyridine on axonal injury and neurodegeneration after traumatic brain injury","authors":"Kryslaine L. Radomski PhD,&nbsp;Xiaomei Zi MS,&nbsp;Genevieve M. Sullivan PhD,&nbsp;Regina C. Armstrong PhD","doi":"10.1016/j.neurot.2026.e01021","DOIUrl":"10.1016/j.neurot.2026.e01021","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e01021"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148951678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}