Neurotherapeutics最新文献_第8页

Brain interstitial fluid pharmacokinetics and therapeutic effect of a BBB penetrating amyloid beta antibody measured by microdialysis 微透析测定血脑屏障穿透性淀粉样抗体脑间质液药动学及治疗效果。

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-06-24 DOI: 10.1016/j.neurot.2026.e00949

Elin Wik, Amelia D. Dahlén, Ulrika Julku, Mengfei Xiong, Wojciech Michno, Stina Syvänen, Dag Sehlin

{"title":"Brain interstitial fluid pharmacokinetics and therapeutic effect of a BBB penetrating amyloid beta antibody measured by microdialysis","authors":"Elin Wik, Amelia D. Dahlén, Ulrika Julku, Mengfei Xiong, Wojciech Michno, Stina Syvänen, Dag Sehlin","doi":"10.1016/j.neurot.2026.e00949","DOIUrl":"10.1016/j.neurot.2026.e00949","url":null,"abstract":"<div><div>The disease-modifying antibody lecanemab for treating Alzheimer's disease (AD) was initially designed to target amyloid-beta (Aβ) protofibrils, i.e. soluble aggregates of Aβ, but it has also been successful in clearing insoluble amyloid plaques in clinical studies. Therefore, this study aimed to investigate how a brain penetrating, bispecific murine variant of lecanemab (RmAb158-scFv8D3) distributes in the brain and interacts with different pools of aggregated Aβ in APP transgenic mice. The alpha-synuclein targeting antibody RmAbSynO2-scFv8D3 was used as control. Further, by performing <em>in vivo</em> high cut-off microdialysis in freely moving animals, brain interstitial fluid (ISF) was continuously collected across 24 h to assess concentrations of free antibody in the brain. <em>Post mortem</em> distribution of the antibodies was analyzed by sequential extraction of brain tissue. RmAb158-scFv8D3 showed rapid ISF clearance as well as a redistribution from brain extracts containing small, soluble Aβ species toward brain extracts containing insoluble, plaque-associated Aβ with time. A treatment effect was detected already at 12 h post injection, whereby the RmAb158-scFv8D3-treated animals showed lower concentrations of the smallest, most soluble Aβ aggregates. Collectively, these findings suggest that within the first 24 h after a single injection of the bispecific RmAb158-scFv8D3 antibody we can capture the antibody's initial brain distribution and interactions with both soluble Aβ aggregates and insoluble, plaque-associated Aβ. These interactions mediate a swift reduction of soluble Aβ, while clearance of insoluble Aβ requires longer treatment time.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 4","pages":"Article e00949"},"PeriodicalIF":7.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318097","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}

引用次数: 0

23 years of mTOR inhibition for tuberous sclerosis: Practical considerations 结核性硬化症23年mTOR抑制：实际考虑。

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-07-10 DOI: 10.1016/j.neurot.2026.e00959

David Neal Franz

引用次数: 0

AAV-mediated Gsx1 gene therapy demonstrates preclinical safety and efficacy in a mouse model of contusion spinal cord injury aav介导的Gsx1基因治疗在小鼠挫伤脊髓损伤模型中显示临床前安全性和有效性

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-09-09 DOI: 10.1016/j.neurot.2026.e00987

Li Cai PhD

引用次数: 0

TMS Motor Cortical Inhibition: Preliminary Analysis Mapping the Cognitive Correlates in People with Schizophrenia TMS运动皮质抑制：精神分裂症患者认知相关因素的初步分析

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-09-09 DOI: 10.1016/j.neurot.2026.e01011

Eugene Bosworth, Samantha Narvaez, Stephanie Hare PhD

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A novel xenon delivery platform for therapeutic cerebroprotection during acute stroke 急性脑卒中治疗性脑保护的新型氙气输送平台

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-09-09 DOI: 10.1016/j.neurot.2026.e01017

KEITH R. BOOHER, Sean I. Savitz MD, Jarek Aronowski MD, Jonathan A. Claypool JD/PhD, Joseph Ollar MS, David McPherson MD, Melvin E. Klegerman PhD, Shaoling Huang MD/PhD

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The Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons with REM Sleep Behavior Disorder (RBD) 合理的免疫系统操作预防快速眼动睡眠行为障碍（RBD）患者突触核病变表现的可能性

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-09-09 DOI: 10.1016/j.neurot.2026.e01019

Ludy Shih, Yoshiaki Yasumizu MD, PhD, Elizabeth Deerhake MD, PhD, Vijaya Reddy BS, Samantha Esposito BS, Sapna Patel BS, Brian Koo MD, Le Zhang PhD, Erika Renkl BA, Jesse Cedarbaum MD, David Hafler MD

引用次数: 0

The ExTINGUISH modified Rankin Scale: A Comprehensive Functional Outcome Measure for NMDAR Encephalitis 灭火器改良Rankin量表：NMDAR脑炎的综合功能结局测量

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-09-09 DOI: 10.1016/j.neurot.2026.e00981

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

引用次数: 0

The NeuroNEXT Gene Therapy Consortium – Contributions to Gene-Based Therapies in Ultra-Rare Neurological Disorders NeuroNEXT基因治疗联盟-对超罕见神经疾病的基因治疗的贡献

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-09-09 DOI: 10.1016/j.neurot.2026.e00990

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

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Zinc as a phase-specific therapeutic target in hypoglycemia-induced brain injury 锌作为低血糖性脑损伤的阶段性治疗靶点。

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-07-09 DOI: 10.1016/j.neurot.2026.e00962

Dong Gyun Ko, Hyun Wook Yang, Hyun Ho Jeong, Min Kyu Park, Bo Young Choi, Seok Joon Won, Raymond A. Swanson, Sang Won Suh

{"title":"Zinc as a phase-specific therapeutic target in hypoglycemia-induced brain injury","authors":"Dong Gyun Ko, Hyun Wook Yang, Hyun Ho Jeong, Min Kyu Park, Bo Young Choi, Seok Joon Won, Raymond A. Swanson, 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}

引用次数: 0

Insights on the cellular mechanisms of intracranial electrical stimulation using optical imaging in preclinical models 应用光学成像技术在临床前模型中观察颅内电刺激的细胞机制。

IF 7.4 2区医学

Neurotherapeutics Pub Date : 2026-07-01 Epub Date: 2026-08-11 DOI: 10.1016/j.neurot.2026.e01043

Cara Ravasio, Mohammed Abumuaileq, Mohigul Nasimova, Jiancheng Xie, Dana C. Shaw, Audrey Lindsay, Catherine J. Chu, Xue Han

{"title":"Insights on the cellular mechanisms of intracranial electrical stimulation using optical imaging in preclinical models","authors":"Cara Ravasio, Mohammed Abumuaileq, Mohigul Nasimova, Jiancheng Xie, Dana C. Shaw, Audrey Lindsay, Catherine J. Chu, 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}

引用次数: 0