Journal of experimental neurology最新文献

N-Acetylcysteine Ameliorates Loss of the Electroretinogram b-wave in a Bardet-Biedl Syndrome Type 10 Mouse Model. n -乙酰半胱氨酸改善Bardet-Biedl综合征10型小鼠视网膜电图b波丢失

Journal of experimental neurology Pub Date : 2025-01-01 DOI: 10.33696/Neurol.6.108

Tyler J Rankin, Sara Mayer, Joseph G Laird, Brianna Lobeck, Emily Kalmanek, Arlene V Drack

{"title":"N-Acetylcysteine Ameliorates Loss of the Electroretinogram b-wave in a Bardet-Biedl Syndrome Type 10 Mouse Model.","authors":"Tyler J Rankin, Sara Mayer, Joseph G Laird, Brianna Lobeck, Emily Kalmanek, Arlene V Drack","doi":"10.33696/Neurol.6.108","DOIUrl":"10.33696/Neurol.6.108","url":null,"abstract":"Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder characterized by retinal degeneration leading to blindness. This study investigates the therapeutic efficacy of N-Acetylcysteine (NAC), an oxygen free radical scavenger, in ameliorating retinal degeneration associated with BBS using a murine model of BBS10. BBS is caused by mutations in BBS genes, the protein products of which are involved in ciliary function; mutant or absent BBS10 protein disrupts the assembly of the BBSome protein complex, disturbing ciliary trafficking and leading to photoreceptor cell dysfunction and death. Photoreceptor function can be assessed using the electroretinogram (ERG), and anatomy can be assessed using optical coherence tomography (OCT) and histology to demonstrate progressive degeneration over time. This study utilizes Bbs10 -/- mice to assess the effect of NAC supplementation on retinal degeneration. Results reveal that NAC supplementation ameliorates the progressive degeneration of the retinal outer nuclear layer (ONL) on OCT and mitigates the loss-of-b-wave ERG phenotype observed in Bbs10 -/- mice. The ERG b-wave is generated by retinal bipolar cells after synapsing with photoreceptors which have been hyperpolarized by light exposure. Reducing the loss-of-b-wave phenotype may indicate improved synaptic function. Synaptic staining demonstrates a correlation between the absence of an electropositive b-wave and mislocalized presynaptic terminals, highlighting the significance of synaptic integrity for retinal function. These findings suggest NAC as a promising therapeutic intervention for managing BBS10-related retinal degeneration.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"6 1","pages":"49-63"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Cascades That Build and Connect Auditory Neurons from Hair Cells to the Auditory Cortex. 从毛细胞到听觉皮层建立和连接听觉神经元的分子级联。

Journal of experimental neurology Pub Date : 2025-01-01

Ebenezer N Yamoah, Gabriela Pavlinkova, Bernd Fritzsch

{"title":"Molecular Cascades That Build and Connect Auditory Neurons from Hair Cells to the Auditory Cortex.","authors":"Ebenezer N Yamoah, Gabriela Pavlinkova, Bernd Fritzsch","doi":"","DOIUrl":"","url":null,"abstract":"Understanding the development of the auditory system is crucial for uncovering the molecular origins of hearing and its related disorders. During this development, spiral ganglion neurons extend peripheral fibers to cochlear hair cells and central projections to the cochlear nuclei, setting up a tonotopic map that connects the ear to the brainstem, enabling frequency-specific sound perception. This sensory information is then integrated bilaterally through a relay involving the superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and the auditory cortex. While anatomical connectivity has been well-documented, recent advancements have revealed gene regulatory networks that coordinate the specification, differentiation, and connectivity of auditory neurons. In this review, we examine the molecular cascades guiding auditory system development, emphasizing transcriptional hierarchies and lineage determinants. Insights into these mechanisms enhance our understanding of auditory circuit formation and provide a critical foundation for therapeutic strategies aimed at addressing congenital and acquired hearing loss.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"6 3","pages":"111-120"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanical Thrombectomy for All LVO – Is It Feasible? – Recent Evidence to Expand the Current Stroke Guidelines 机械血栓切除术治疗所有 LVO - 可行吗？- 扩展现行卒中指南的最新证据

Journal of experimental neurology Pub Date : 2024-01-30 DOI: 10.33696/neurol.5.084

Jindong Xu, Cortney de la Torre, Devon Shafer, Margely Carrion-Carrero, Pramod Sethi

引用次数: 0

Could Neonatal Electroclinical Syndromes Orchestrate Diagnosis and Treatment? 新生儿临床电综合征能否协调诊断和治疗？

Journal of experimental neurology Pub Date : 2024-01-30 DOI: 10.33696/neurol.5.083

Rene Andrade Machado

{"title":"Could Neonatal Electroclinical Syndromes Orchestrate Diagnosis and Treatment?","authors":"Rene Andrade Machado","doi":"10.33696/neurol.5.083","DOIUrl":"https://doi.org/10.33696/neurol.5.083","url":null,"abstract":"Introduction: Neonatal seizures are associated with neurodevelopmental impairments. Implementing long-term video-EEG monitoring in the neonatal intensive care unit became the gold standard for seizure diagnosis. During the neonatal period, seizures can be associated with an acute brain insult called acute symptomatic seizures (ASS) or being part of neonatal epilepsy that may have a structural, metabolic, or genetic cause. This distinction impacts patient workup and management. Objectives: To facilitate a guide to differentiate ASS from neonatal epilepsy, and to correlate different electroclinical seizure patterns with a specific etiology. Methods: A narrative review was performed. MEDLINE, Embase, and PubMed were used to gather data for this narrative review. The following keywords were applied to focus on original research and case reports: epileptic encephalopathy, developmental Epileptic encephalopathy and neonatal seizures, neonatal genetic encephalopathies, Otahara syndrome, neonatal channelopathies, and neonatal seizure classification. Conclusions: Strict electroclinical semiology is the backbone for diagnosing neonatal seizures. The EEG and ictal semiology help with the diagnosis and the treatment. The neonatal seizure classification should be expanded to include the EEG pattern. Lumping them in a better classificatory system will prevent unnecessary and hazardous medication.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"66 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140481193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Definition and Characteristics of Multiple Sclerosis with Predominant Cognitive Presentation 以认知为主要表现的多发性硬化症的定义和特征

Journal of experimental neurology Pub Date : 2024-01-30 DOI: 10.33696/neurol.5.086

Amanda Fiori Cavassani, Álix Djone Berté, Andressa Ribeiro Pinto, Marcus Vinicius Magno Gonçalves, Gabriel de Deus Vieira

引用次数: 0

Diagnosis and Treatment of Normal Pressure Hydrocephalus and Repeated Subdural Hematoma and Effusion after Ventriculoperitoneal Shunt in the Elderly: A Case Report 老年人脑室腹腔分流术后正常压力脑积水和反复硬膜下血肿及渗出的诊断与治疗：病例报告

Journal of experimental neurology Pub Date : 2024-01-30 DOI: 10.33696/neurol.5.085

Qing-Yong Wang, Qingjun Li

{"title":"Diagnosis and Treatment of Normal Pressure Hydrocephalus and Repeated Subdural Hematoma and Effusion after Ventriculoperitoneal Shunt in the Elderly: A Case Report","authors":"Qing-Yong Wang, Qingjun Li","doi":"10.33696/neurol.5.085","DOIUrl":"https://doi.org/10.33696/neurol.5.085","url":null,"abstract":"Idiopathic normal pressure hydrocephalus (iNPH) is a special type of hydrocephalus that is characterized by cognitive decline, gait disturbance, and urinary incontinence. It can lead to dementia and bedridden within 1-3 years. Without surgical treatment in time, the prognosis was bleak. We report an iNPH case misdiagnosed with Alzheimer’s disease, with a disease course of 3 years. The main manifestations of the patient were walking impairment, memory loss, urinary incontinence, repeated falls, and hallucinations, bedridden in the late stage, with a modified Rankin Scale (mRS):5. After undergoing the ventriculoperitoneal shunt, due to the low shunt pressure, the patient developed severe headache, repeated and severe subdural hemorrhage and effusion. After adjusting the shunt pressure in time, the patient recovered well with an mRS: 3, which was inconsistent with the previous belief that the operation was ineffective for patients with a disease course of more than 3 years. This case suggests that elderly patients with iNPH can still benefit from timely surgery even if the disease course of more than 3 years. Special attention should be paid after the operation, and the CSF shunt pressure should avoid setting too low, which may induce serious complications such as subdural hemorrhage or effusion.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140484582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Case Report of Rheumatoid Meningitis – A Rare Condition Presenting with Neurological Deficits 类风湿性脑膜炎病例报告--一种表现为神经功能缺损的罕见疾病

Journal of experimental neurology Pub Date : 2024-01-10 DOI: 10.33696/neurol.4.081

Arun Swaminathan, Arvind Ramesh

引用次数: 0

CCR3 Expression in Relation to Delayed Microbleeds in a Rat Model of Large Vessel Occlusion. 大血管闭塞大鼠模型中 CCR3 表达与延迟性微出血的关系

Journal of experimental neurology Pub Date : 2024-01-01 DOI: 10.33696/neurol.5.082

Sydney M Claypoole, Jacqueline A Frank, Sarah J Messmer, Keith R Pennypacker

{"title":"CCR3 Expression in Relation to Delayed Microbleeds in a Rat Model of Large Vessel Occlusion.","authors":"Sydney M Claypoole, Jacqueline A Frank, Sarah J Messmer, Keith R Pennypacker","doi":"10.33696/neurol.5.082","DOIUrl":"10.33696/neurol.5.082","url":null,"abstract":"Thirty percent of ischemic stroke patients develop vascular cognitive impairment and dementia (VCID) within 1 year of stroke onset. The expression of C-C motif chemokine receptor 3 (CCR3) is associated with endothelial dysfunction and memory impairment. CCR3 has been reported to increase after experimental stroke and in human stroke patients. Using an in vivo model of stroke, our study aims to link CCR3 expression with endothelial dysfunction in this rodent stroke model.Methods: 5-hour transient Middle Cerebral Artery Occlusion (5t-MCAO) or sham surgery was performed on rats and tissue collected at 3- and 30-days post-stroke. We measured the change in expression of CCR3 and its ligands in the venous blood before and after occlusion in the rat model.Immunohistochemistry was performed on consecutive coronal brain sections using Prussian blue to visualize microbleeds and DAB to visualize CCR3. Images were quantified using HALO.Results: Using linear regression, we found that increased expression of CCR3 and its ligands after stroke were positively correlated with infarct volume. CCR3 expression was significantly increased in the ipsilateral hemisphere at 30 days post 5t-MCAO. Prussian blue staining was significantly increased in ipsilateral sections at 30 days post-stroke. Immunostaining for CCR3 was primarily detected in endothelium in areas of Prussian blue staining.Conclusions: Our results demonstrate that CCR3 expression is associated with the presence of microbleeds at 30 days but not 3 days post-stroke in the ipsilateral hemisphere, and further supports the link between CCR3 and the endothelial dysfunction that is associated with VCID. CCR3 and its inflammatory pathway is a potential target for reducing endothelial dysfunction after ischemic stroke that may lead to VCID.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"5 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebrovascular Dysfunction in Alzheimer's Disease and Transgenic Rodent Models. 阿尔茨海默病和转基因啮齿动物模型中的脑血管功能障碍

Journal of experimental neurology Pub Date : 2024-01-01 DOI: 10.33696/neurol.5.087

Xing Fang, Fan Fan, Jane J Border, Richard J Roman

{"title":"Cerebrovascular Dysfunction in Alzheimer's Disease and Transgenic Rodent Models.","authors":"Xing Fang, Fan Fan, Jane J Border, Richard J Roman","doi":"10.33696/neurol.5.087","DOIUrl":"10.33696/neurol.5.087","url":null,"abstract":"Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementia (ADRD) are the primary causes of dementia that has a devastating effect on the quality of life and is a tremendous economic burden on the healthcare system. The accumulation of extracellular beta-amyloid (Aβ) plaques and intracellular hyperphosphorylated tau-containing neurofibrillary tangles (NFTs) in the brain are the hallmarks of AD. They are also thought to be the underlying cause of inflammation, neurodegeneration, brain atrophy, and cognitive impairments that accompany AD. The discovery of APP, PS1, and PS2 mutations that increase Aβ production in families with early onset familial AD led to the development of numerous transgenic rodent models of AD. These models have provided new insight into the role of Aβ in AD; however, they do not fully replicate AD pathology in patients. Familial AD patients with mutations that elevate the production of Aβ represent only a small fraction of dementia patients. In contrast, those with late-onset sporadic AD constitute the majority of cases. This observation, along with the failure of previous clinical trials targeting Aβ or Tau and the modest success of recent trials using Aβ monoclonal antibodies, has led to a reappraisal of the view that Aβ accumulation is the sole factor in the pathogenesis of AD. More recent studies have established that cerebral vascular dysfunction is one of the earliest changes seen in AD, and 67% of the candidate genes linked to AD are expressed in the cerebral vasculature. Thus, there is an increasing appreciation of the vascular contribution to AD, and the National Institute on Aging (NIA) and the Alzheimer's Disease Foundation recently prioritized it as a focused research area. This review summarizes the strengths and limitations of the most commonly used transgenic AD animal models and current views about the contribution of Aβ accumulation versus cerebrovascular dysfunction in the pathogenesis of AD.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"5 2","pages":"42-64"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein Assembly Modulation: A New Approach to Amyotrophic Lateral Sclerosis (ALS) Therapeutics. 蛋白质组装调节：肌萎缩侧索硬化（ALS）治疗的新方法。

Journal of experimental neurology Pub Date : 2024-01-01 DOI: 10.33696/Neurol.5.103

Shao Feng Yu, Kumar Paulvannan, Dennis Solas, Anuradha F Lingappa, Ana Raquel Moreira, Shriya Sahu, Maya Michon, Amanda Macieik, Danielle Goldsmith, Nicholas DeYarman, Suguna Mallesh, M Dharma Prasad, Claudia Maios, Kai Ruan, Giulio S Tomassy, Elizabeth Jensen, Emma McGuirk, Verian Bader, Andreas Mueller-Schiffmann, Jonathan C Reed, Jaisri R Lingappa, Vinod Asundi, Shi Hong, Steve Jacobsen, Nicholas Brandon, Lyle Ostrow, Tom Lloyd, J Alex Parker, Kim A Staats, Justin Ichida, James C Dodge, Debendranath Dey, Carsten Korth, Suganya Selvarajah, Vishwanath R Lingappa, Jeffrey Rosenfeld

{"title":"Protein Assembly Modulation: A New Approach to Amyotrophic Lateral Sclerosis (ALS) Therapeutics.","authors":"Shao Feng Yu, Kumar Paulvannan, Dennis Solas, Anuradha F Lingappa, Ana Raquel Moreira, Shriya Sahu, Maya Michon, Amanda Macieik, Danielle Goldsmith, Nicholas DeYarman, Suguna Mallesh, M Dharma Prasad, Claudia Maios, Kai Ruan, Giulio S Tomassy, Elizabeth Jensen, Emma McGuirk, Verian Bader, Andreas Mueller-Schiffmann, Jonathan C Reed, Jaisri R Lingappa, Vinod Asundi, Shi Hong, Steve Jacobsen, Nicholas Brandon, Lyle Ostrow, Tom Lloyd, J Alex Parker, Kim A Staats, Justin Ichida, James C Dodge, Debendranath Dey, Carsten Korth, Suganya Selvarajah, Vishwanath R Lingappa, Jeffrey Rosenfeld","doi":"10.33696/Neurol.5.103","DOIUrl":"10.33696/Neurol.5.103","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS) is a devastating and progressive neurodegenerative disease with a complex, multifactorial pathophysiology, culminating in death of motor neurons. We introduce a new mechanism of ALS pathogenesis via study of a novel drug-like small molecule series that targets a subset of protein disulfide isomerase (PDI) within a previously largely unappreciated transient and energy-dependent multi-protein complex enriched for proteins of the ALS interactome. This drug, found by a novel phenotypic screen, has activity in cellular models for both familial and sporadic ALS, as well as in transgenic worms, flies, and mice bearing a diversity of human genes with ALS-associated mutations. The hit compound was initially identified as a modulator of human immunodeficiency virus (HIV) capsid assembly in cell-free protein synthesis and assembly (CFPSA) systems, with demonstrated antiviral activity against infectious HIV in cell culture. Its advancement for ALS-therapeutics, subsequent separation of activity against HIV and ALS into separate chemical subseries through structure-activity-relationship (SAR) optimization, and identification of the drug target by affinity chromatography as shown here, may provide insights into the molecular mechanisms governing pathophysiology of disordered homeostasis relevant to ALS.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"5 4","pages":"210-230"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0