Neurotherapeutics最新文献

Gut microbiota immune cross-talk in amyotrophic lateral sclerosis. 肌萎缩性脊髓侧索硬化症中的肠道微生物群免疫交叉对话。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-11-06 DOI: 10.1016/j.neurot.2024.e00469

Megha Kaul, Debanjan Mukherjee, Howard L Weiner, Laura M Cox

引用次数: 0

The brain pathobiome in Alzheimer's disease. 阿尔茨海默病的大脑病理生物群。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-11-06 DOI: 10.1016/j.neurot.2024.e00475

Nanda Kumar Navalpur Shanmugam, William A Eimer, Deepak K Vijaya Kumar, Rudolph E Tanzi

引用次数: 0

Gut microbiota dysbiosis and neurologic diseases: New Horizon with potential diagnostic and therapeutic impact. 肠道微生物群失调与神经系统疾病：对诊断和治疗具有潜在影响的新视野。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-11-01 DOI: 10.1016/j.neurot.2024.e00478

Ali Keshavarzian, Sangram S Sisodia

引用次数: 0

Thinking outside the brain: Gut microbiome influence on innate immunity within neurodegenerative disease. 脑外思考：肠道微生物组对神经退行性疾病先天免疫的影响

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-31 DOI: 10.1016/j.neurot.2024.e00476

Andrea R Merchak, MacKenzie L Bolen, Malú Gámez Tansey, Kelly B Menees

{"title":"Thinking outside the brain: Gut microbiome influence on innate immunity within neurodegenerative disease.","authors":"Andrea R Merchak, MacKenzie L Bolen, Malú Gámez Tansey, Kelly B Menees","doi":"10.1016/j.neurot.2024.e00476","DOIUrl":"https://doi.org/10.1016/j.neurot.2024.e00476","url":null,"abstract":"The complex network of factors that contribute to neurodegeneration have hampered the discovery of effective preventative measures. While much work has focused on brain-first therapeutics, it is becoming evident that physiological changes outside of the brain are the best target for early interventions. Specifically, myeloid cells, including peripheral macrophages and microglia, are a sensitive population of cells whose activity can directly impact neuronal health. Myeloid cell activity includes cytokine production, migration, debris clearance, and phagocytosis. Environmental measures that can modulate these activities range from toxin exposure to diet. However, one of the most influential mediators of myeloid fitness is the gut microenvironment. Here, we review the current data about the role of myeloid cells in gastrointestinal disorders, Parkinson's disease, dementia, and multiple sclerosis. We then delve into the gut microbiota modulating therapies available and clinical evidence for their use in neurodegeneration. Modulating lifestyle and environmental mediators of inflammation are one of the most promising interventions for neurodegeneration and a systematic and concerted effort to examine these factors in healthy aging is the next frontier.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "A real-time neurophysiologic stress test for the aging brain: Novel perioperative and ICU applications of EEG in older surgical patients" Neurotherapeutics 20 (4) (2023) 975-1000. 老化大脑的实时神经生理学压力测试：神经治疗学 20 (4) (2023) 975-1000。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-30 DOI: 10.1016/j.neurot.2024.e00473

Miles Berger, David Ryu, Melody Reese, Steven McGuigan, Lisbeth A Evered, Catherine C Price, David A Scott, M Brandon Westover, Roderic Eckenhoff, Laura Bonanni, Aoife Sweeney, Claudio Babiloni

引用次数: 0

Risk of angioedema and thrombolytic therapy among stroke patients: An analysis of data from the FDA Adverse Event Reporting System database. 中风患者血管性水肿与溶栓治疗的风险：美国食品和药物管理局不良事件报告系统数据库数据分析。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-30 DOI: 10.1016/j.neurot.2024.e00474

Hunong Xiang, Yu Ma, Xiaochao Luo, Jian Guo, Minghong Yao, Yanmei Liu, Ke Deng, Xin Sun, Ling Li

{"title":"Risk of angioedema and thrombolytic therapy among stroke patients: An analysis of data from the FDA Adverse Event Reporting System database.","authors":"Hunong Xiang, Yu Ma, Xiaochao Luo, Jian Guo, Minghong Yao, Yanmei Liu, Ke Deng, Xin Sun, Ling Li","doi":"10.1016/j.neurot.2024.e00474","DOIUrl":"https://doi.org/10.1016/j.neurot.2024.e00474","url":null,"abstract":"The angioedema risk may vary among stroke patients receiving different thrombolytic agents. This study aimed to investigate the angioedema risk associated with different thrombolytic agents and to identify associated risk factors. We conducted a large-scale retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database. Stroke patients receiving thrombolytic therapy (i.e., alteplase or tenecteplase) were identified, and the associations with angioedema were explored using disproportionality analysis and time-to-onset analysis. Additionally, we used adapted Bradford Hill criteria to confirm these associations. Risk factors for angioedema were explored using stepwise logistic regression. A total of 17,776 stroke patients were included, with 2973 receiving alteplase and 278 receiving tenecteplase. Disproportionality analysis revealed that angioedema might be associated with alteplase (adjusted ROR [aROR] 5.13 [95 % CI, 4.55-5.79]) or tenecteplase (aROR 2.72 [95 % CI, 1.98-3.67]). The adapted Bradford Hill criteria suggested a probable causal relationship between alteplase and angioedema, whereas there was insufficient evidence of a probable causal relationship with tenecteplase. Multivariate analysis revealed that ACE-inhibitors use (aROR 9.73 [95 % CI, 7.29-12.98]), female sex (aROR 1.38 [95 % CI, 1.13-1.67]) and hypertension (aROR 2.11 [95 % CI, 1.52-2.92]) were significant risk factors for angioedema among alteplase-treated stroke patients. Our study suggested that alteplase is associated with a greater risk of angioedema among stroke patients, but there is insufficient evidence to support an association between tenecteplase and angioedema. Clinicians should be vigilant for this potentially life-threatening complication, particularly in patients with identified risk factors. It is also prudent to consider tenecteplase as an alternative, if available.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut microbial metabolism in Alzheimer's disease and related dementias. 阿尔茨海默病和相关痴呆症的肠道微生物代谢。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-26 DOI: 10.1016/j.neurot.2024.e00470

Jea Woo Kang, Vaibhav Vemuganti, Jessamine F Kuehn, Tyler K Ulland, Federico E Rey, Barbara B Bendlin

{"title":"Gut microbial metabolism in Alzheimer's disease and related dementias.","authors":"Jea Woo Kang, Vaibhav Vemuganti, Jessamine F Kuehn, Tyler K Ulland, Federico E Rey, Barbara B Bendlin","doi":"10.1016/j.neurot.2024.e00470","DOIUrl":"https://doi.org/10.1016/j.neurot.2024.e00470","url":null,"abstract":"Multiple studies over the last decade have established that Alzheimer's disease and related dementias (ADRD) are associated with changes in the gut microbiome. These alterations in organismal composition result in changes in the abundances of functions encoded by the microbial community, including metabolic capabilities, which likely impact host disease mechanisms. Gut microbes access dietary components and other molecules made by the host and produce metabolites that can enter circulation and cross the blood-brain barrier (BBB). In recent years, several microbial metabolites have been associated with or have been shown to influence host pathways relevant to ADRD pathology. These include short chain fatty acids, secondary bile acids, tryptophan derivatives (such as kynurenine, serotonin, tryptamine, and indoles), and trimethylamine/trimethylamine N-oxide. Notably, some of these metabolites cross the BBB and can have various effects on the brain, including modulating the release of neurotransmitters and neuronal function, inducing oxidative stress and inflammation, and impacting synaptic function. Microbial metabolites can also impact the central nervous system through immune, enteroendocrine, and enteric nervous system pathways, these perturbations in turn impact the gut barrier function and peripheral immune responses, as well as the BBB integrity, neuronal homeostasis and neurogenesis, and glial cell maturation and activation. This review examines the evidence supporting the notion that ADRD is influenced by gut microbiota and its metabolites. The potential therapeutic advantages of microbial metabolites for preventing and treating ADRD are also discussed, highlighting their potential role in developing new treatments.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebellar deep brain stimulation as a dual-function therapeutic for restoring movement and sleep in dystonic mice. 小脑深部刺激作为一种双重功能疗法，可恢复肌张力障碍小鼠的运动和睡眠。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-23 DOI: 10.1016/j.neurot.2024.e00467

Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

{"title":"Cerebellar deep brain stimulation as a dual-function therapeutic for restoring movement and sleep in dystonic mice.","authors":"Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe","doi":"10.1016/j.neurot.2024.e00467","DOIUrl":"10.1016/j.neurot.2024.e00467","url":null,"abstract":"Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect of cerebellar DBS in two genetic mouse models with dystonia that exhibit sleep defects-Ptf1aCre;Vglut2fx/fx and Pdx1Cre;Vglut2fx/fx-which have overlapping cerebellar circuit miswiring defects but differing severity in motor phenotypes. By targeting DBS to the fiber tracts located between the cerebellar fastigial and the interposed nuclei (FN + INT-DBS), we modulated sleep dysfunction by enhancing sleep quality and timing. This DBS paradigm improved wakefulness and rapid eye movement sleep in both mutants. Additionally, the latency to reach REM sleep, a deficit observed in human dystonia patients, was reduced in both models. Cerebellar DBS also induced alterations in the electrocorticogram (ECoG) patterns that define sleep states. As expected, DBS reduced the severe dystonic twisting motor symptoms that are observed in the Ptf1aCre;Vglut2fx/fx mice. These findings highlight the potential for using cerebellar DBS to simultaneously improve sleep and reduce motor dysfunction in dystonia and uncover its potential as a dual-effect in vivo therapeutic strategy.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroplasticity in the transition from acute to chronic pain. 从急性疼痛到慢性疼痛转变过程中的神经可塑性。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-21 DOI: 10.1016/j.neurot.2024.e00464

Qingbiao Song, Sihan E, Zhiyu Zhang, Yingxia Liang

引用次数: 0

Post-injury treatment with 7,8-dihydroxyflavone attenuates white matter pathology in aged mice following focal traumatic brain injury. 损伤后使用 7,8- 二羟基黄酮可减轻老年小鼠局灶性脑外伤后的白质病变。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-19 DOI: 10.1016/j.neurot.2024.e00472

Georgios Michalettos, Fredrik Clausen, Elham Rostami, Niklas Marklund

{"title":"Post-injury treatment with 7,8-dihydroxyflavone attenuates white matter pathology in aged mice following focal traumatic brain injury.","authors":"Georgios Michalettos, Fredrik Clausen, Elham Rostami, Niklas Marklund","doi":"10.1016/j.neurot.2024.e00472","DOIUrl":"https://doi.org/10.1016/j.neurot.2024.e00472","url":null,"abstract":"Traumatic brain injury (TBI) is a major cause of morbidity and mortality, not least in the elderly. The incidence of aged TBI patients has increased dramatically during the last decades. High age is a highly negative prognostic factor in TBI, and pharmacological treatment options are lacking. We used the controlled cortical impact (CCI) TBI model in 23-month-old male and female mice and analyzed the effect of post-injury treatment with 7,8 dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor (BDNF)-mimetic compound, on white matter pathology. Following CCI or sham injury, mice received subcutaneous 7,8-DHF injections (5 mg/kg) 30 min post-injury and were sacrificed on 2, 7 or 14 days post-injury (dpi) for histological and immunofluorescence analyses. Histological assessment with Luxol Fast Blue (LFB)/Cresyl Violet stain showed that administration of 7,8-DHF resulted in preserved white matter tissue at 2 and 7 dpi with no difference in cortical tissue loss at all investigated time points. Treatment with 7,8-DHF led to reduced axonal swellings at 2 and 7 dpi, as visualized by SMI-31 (Neurofilament Heavy Chain) immunofluorescence, and reduced number of TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling)/CC1-positive mature oligodendrocytes at 2 dpi in the perilesional white matter. Post-injury proliferation of Platelet-derived Growth Factor Receptor (PDGFRα)-positive oligodendodrocyte progenitor cells was not altered by 7,8-DHF. Our results suggest that 7,8-DHF can attenuate white matter pathology by mitigating axonal injury and oligodendrocyte death in the aged mouse brain following TBI. These data argue that further exploration of 7,8-DHF towards clinical use is warranted.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0