类淋巴系统与中枢神经系统疾病研究进展

类淋巴系统是中枢神经系统特有网络,该系统可清除大脑积累的代谢废物,维持中枢神经系统的内环境稳态。该系统在睡眠状态下相对活跃,生理功能受到多种因素影响。非侵入性影像技术评估类淋巴系统功能的应用推动了临床研究的开展。越来越多的研究表明,类淋巴系统功能与神经退行性疾病、脑血管病等多种中枢神经系统疾病的发病机制相关。类淋巴系统有望成为预测中枢神经系统疾病预后及临床干预疗效的新靶点。     

睡眠对大脑清除代谢产物的影响：基于类淋巴系统的思考

阿尔茨海默病、帕金森病等神经系统退行性疾病常伴随着规律睡眠结构的破坏, 其发病机制可能与中枢神经系统废物的堆积有关。类淋巴系统本质是动脉周围脑脊液流入途径和周围静脉清除途径, 在功能上依赖星形胶质细胞终足上水通道蛋白-4所支持的间质大流量耦合, 也称胶质淋巴系统。清除大脑中废物蛋白质的类淋巴系统主要在睡眠期间活跃。睡眠质量随着年龄的增长而下降, 而类淋巴系统也会随着年龄的增长而退化, 这表明睡眠障碍与神经退行性的症状进展之间密切相关, 类淋巴系统作为纽带将两者紧紧相连。睡眠、衰老、代谢废物和类淋巴系统网格式的交互联系为中枢神经系统退行性疾病的发病机制提供了新的线索, 类淋巴系统可能构成其治疗上的新靶点。本文主要就近年来睡眠、睡眠障碍对类淋巴系统循环影响的研究进展进行综述, 并且提出, 对睡眠进行干预或可延缓类淋巴系统功能的损伤甚至恢复类淋巴系统功能, 进而改善疾病的发生发展进程。     

基于类淋巴系统机制治疗阿尔茨海默病的研究进展

阿尔茨海默病(Alzheimer disease, AD)是一种起病隐匿,呈进行性发展的神经系统退行性疾病。近些年,越来越多的研究发现类淋巴系统与AD中的异常蛋白清除障碍密切相关。本文总体阐述了类淋巴系统的发现及其与AD的关系,重点对其对脑内β-淀粉样蛋白(amyloid-beta protein, Aβ)、tau蛋白的清除功能及影响因素,以及基于类淋巴系统机制治疗AD的最新研究成果进行综述。     

大脑淋巴系统的概览及临床意义

传统观念认为大脑是"免疫豁免"器官，对病原体和肿瘤的免疫监视有限。随着研究的逐渐深入，神经学家在中枢神经系统（CNS）中窥探到淋巴系统的踪迹。最近的几项研究证实了脑膜淋巴管的存在，并对其进行了初步描述。脑淋巴管解剖结构和功能的明确，揭开了颅内流体动力学的大致全貌，解答了临床中许多疑问。更重要的是，这些发现为神经系统相关疾病的治疗开辟了新的途径。该文通过回顾中枢淋巴网络的研究历史，总结出大脑组织液（ISF）和脑脊液（CSF）的循环过程，并简要介绍了该淋巴系统在多种疾病的病理生理过程及治疗中的意义。     

胶质淋巴系统在糖尿病相关认知功能障碍中的研究进展

近年来越来越多的研究表明, 胶质淋巴系统在糖尿病中受到损伤, 与糖尿病相关认知功能障碍关系密切。本研究围绕糖尿病对胶质淋巴系统的直接影响和间接影响, 以及胶质淋巴系统在糖尿病相关认知功能障碍发病机制中的影像学证据综述如下, 以期促进对该领域的了解。     

中枢神经系统淋巴循环与相关疾病研究进展

淋巴系统是循环系统的重要组成部分,中枢神经系统无衬有内皮细胞的淋巴管,但存在结构和功能意义上的淋巴循环。Virchow-Robin间隙是中枢淋巴循环的主要结构,具有与外周淋巴管相似的功能,对维持中枢神经系统正常生理功能具有重要作用。Virchow-Robin间隙具有淋巴引流功能,脑间质液中的大分子物质主要经此途径引流;Virchow-Robin间隙也是免疫监视的重要组成部分。中枢淋巴循环在淋巴滞留性脑病、脱髓鞘疾病、中枢神经系统肿瘤、中枢神经系统感染和蛋白质异常折叠性疾病的发生与发展过程中发挥关键作用。     

肠道微生物与常见中枢神经系统疾病相关性的研究进展

肠道微生物不仅局限作用于胃肠道,可以通过脑肠轴对大脑功能产生重要影响.肠道微生物结构与功能的改变与阿茨海默病、帕金森病、多发性硬化、脑卒中等一系列常见中枢神经系统疾病密切相关,通过改善肠道微生物的微生态疗法有望成为预防和治疗中枢神经系统疾病的有效途径.现对近年来肠道微生物与常见中枢神经系统疾病的相关研究进展进行综述.     

血脑屏障完整性与中枢神经系统疾病的发展和转归的相关性研究进展

血脑屏障(BBB)完整性的破坏存在于多种中枢神经系统疾病中,包括神经炎性疾病和神经退行性病变。氧化应激、炎症反应等病理因素均能导致血脑屏障破坏,进而造成或加重神经损伤。血脑屏障结构和功能的完整性与神经系统疾病进程密切相关,参与疾病的发生和发展,并影响治疗预后。本文将对中枢神经系统疾病中血脑屏障破坏的机制及其与疾病的发展转归关系作一综述。     

星形胶质细胞与帕金森病相关基因的研究进展

正帕金森病(Parkinson’s disease,PD)是一种患病率随年龄增长而增加的神经系统变性疾病,约影响65岁以上人群的1%。帕金森病病因在大多数患者中仍然未知,但目前普遍认为与环境、遗传和年龄等因素相关,其中遗传因素在疾病的发展进程中起重要作用。星形胶质细胞(AS)是重要的神经胶质细胞,广泛参与了中枢神经系统(CNS)的功能发     

吸入麻醉药对中枢神经系统功能的影响

现今临床常用的吸入麻醉药如氧化亚氮、恩氟烷、异氟烷、七氟烷和地氟烷等在吸入麻醉过程中,皆会对患者的中枢神经系统和/或脑功能产生一定程度的影响.不同的药物,不同的吸入浓度和持续时间,对脑电活动抑制程度不同.吸入麻醉药与不同的静脉麻醉药联合应用,其脑功能受影响的特点也有所差异.此外,正常或疾病状态下的中枢神经系统和/或脑组织、脑电活动和血管功能,对各种吸入麻醉药的反应也不相互一致.详细了解临床常用的各种吸入麻醉药对脑功能影响的特点,掌握正确的使用方法,对颅脑和中枢神经系统疾病患者手术和麻醉安全尤为重要.本文结合近期国外相关文献,针对吸入麻醉药对脑电生理活动、脑血管自动调节功能、脑组织代谢功能和颅内压影响等手术和麻醉医生关心的热点问题,进行全面阐述,对临床工作有重要指导意义.     

Klotho基因在神经变性病中的研究进展

Klotho(Kl)是一种衰老抑制基因,其对CNS有保护作用,与神经变性疾病如Alzheimer's病、帕金森病等具有明显的相关性.在Alzheimer's病中,Kl对抗β淀粉样物质对海马神经元造成的损害,细胞层面上能显著改善长时程记忆基础中的N-甲基-D-天冬氨酸受体结构功能和网络反应敏感性,分子层面上能调节硫氧还蛋...     

Does COVID-19 increase the risk of neuropsychiatric sequelae? Evidence from a mendelian randomization approach

Observational studies based on electronic health records (EHR) report an increased risk of neurological/neuropsychiatric sequelae for patients who have had coronavirus disease 2019 (COVID-19). However, these studies may suffer from biases such as unmeasured confounding, residual reverse causality, or lack of precision in EHR-based diagnoses. To rule out these biases, we tested causal links between COVID-19 and different potential neurological/neuropsychiatric sequelae through a two-sample Mendelian randomization analysis of summary statistics from large Genome-Wide Association Scans of susceptibility to COVID-19 and different neurological and neuropsychiatric disorders, including major depression, anxiety, schizophrenia, stroke, Parkinson’s and Alzheimer’s diseases. We found robust evidence suggesting that COVID-19 – notably the hospitalized and most severe forms – carries an increased risk of neuropsychiatric sequelae, particularly Alzheimer’s disease, and to a lesser extent anxiety disorder. In line with a large longitudinal EHR-based study, this evidence was stronger for more severe COVID-19 forms. These results call for a targeted screening strategy to tackle the post-COVID neuropsychiatric pandemic.     

Modulation of mind: therapeutic neuromodulation for cognitive disability

Neuromodulation using deep brain stimulation (DBS) has become an established therapy for the treatment of certain disorders such as Parkinson’s disease and tremors. Recent advances in surgical and imaging techniques further decrease the surgical risk associated with these procedures. Symptoms such as tremor, bradykinesia, rigidity and gait disturbances can be significantly controlled with DBS. This results in an opportunity to decrease anti-parkinsonism medications, and their dyskinetic side-effects. Following the success of DBS in the management of movement disorders, the role of this therapy is being extensively studied in more complex disorders that involve cognition and behavior. The inherent complexity in cognitive circuitry makes neuromodulation using DBS more difficult than in movement disorders. The goal of DBS surgery in these diseases is not only to slow the cognitive decline, but also restoration of function and ultimately improvement in the quality of life. DBS as a treatment for patients with advanced dementia holds significant promise in delaying or reversing the progressive cognitive decline by enhancing connectivity in the memory networks. In appropriately selected patients this potentially reversible surgical therapy can lead to a significant improvement in the quality of life and reduce the burden on patients, families and the healthcare system. This review focuses on the recent and future studies involving neuromodulation for cognitive disorders such as Alzheimer’s disease and Huntington’s disease.     

Brain aging: A Ianus-faced player between health and neurodegeneration

Neurodegenerative diseases are incurable debilitating disorders characterized by structural and functional neuronal loss. Approximately 30 million people are affected worldwide, and this number is predicted to reach more than 150 million by 2050. Neurodegenerative disorders include Alzheimer’s, Parkinson’s, and prion diseases among others. These disorders are characterized by the accumulation of aggregating proteins forming amyloid, responsible for the disease-associated pathological lesions. The aggregation of amyloidogenic proteins can result either in gaining of toxic functions, derived from the damage provoked by these deposits in affected tissue, or in a loss of functions, due to the sequestration and the consequent inability of the aggregating protein to ensure its physiological role. While it is widely accepted that aging represents the main risk factor for neurodegeneration, there is still no clear cut-off line between the two conditions. Indeed, many of the pathways that are commonly altered in neurodegeneration—misfolded protein accumulation, chronic inflammation, mitochondrial dysfunction, impaired iron homeostasis, epigenetic modifications—have been often correlated also with healthy aging. This overlap could be explained by the fact that the continuous accumulation of cellular damages, together with a progressive decline in metabolic efficiency during aging, makes the neurons more vulnerable to toxic injuries. When a given threshold is exceeded, all these alterations might give rise to pathological phenotypes that ultimately lead to neurodegeneration.     

Papel de la microbiota intestinal en el desarrollo de diferentes enfermedades neurológicas

IntroductionIn recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined.DevelopmentWe review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis.ConclusionsThe body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids.Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.     

Is there a role for ghrelin in central dopaminergic systems? Focus on nigrostriatal and mesocorticolimbic pathways

The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer. Ghrelin and its receptor, which is expressed throughout the brain, play an important role in motivation and reward. Ghrelin finely modulates the mesencephalic dopaminergic signaling and is thus currently studied in pathological conditions including dopamine-related disorders. Dopamine regulates motivated behaviors, modulating reward processes, emotions and motor functions to enable the survival of individuals and species. Numerous dopamine-related disorders including Parkinson’s disease or eating disorders like anorexia nervosa involve altered ghrelin levels. However, despite the growing interest for ghrelin in these pathological conditions, global integrative studies investigating its role in brain dopaminergic structures are still lacking. In this review, we discuss the role of ghrelin on dopaminergic neurons and its relevance in the search for new therapeutics for Parkinson’s disease- and anorexia nervosa-related dopamine deficits.     

Achieving brain clearance and preventing neurodegenerative diseases—A glymphatic perspective

Age-related neurodegenerative diseases are a growing burden to society, and many are sporadic, meaning that the environment, diet and lifestyle play significant roles. Cerebrospinal fluid (CSF)-mediated clearing of brain waste products via perivascular pathways, named the glymphatic system, is receiving increasing interest, as it offers unexplored perspectives on understanding neurodegenerative diseases. The glymphatic system is involved in clearance of metabolic by-products such as amyloid-β from the brain, and its function is believed to lower the risk of developing some of the most common neurodegenerative diseases. Here, we present magnetic resonance imaging (MRI) data on the heart cycle’s control of CSF flow in humans which corroborates findings from animal studies. We also review the importance of sleep, diet, vascular health for glymphatic clearance and find that these factors are also known players in brain longevity.     

Synopsis on the Linkage of Alzheimer's and Parkinson's Disease with Chronic Diseases

Neurodegeneration is the progressive loss of neuronal structure and function, which ultimately leads to neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and Huntington's disease. Even after the recent significant advances in neurobiology, the above‐mentioned disorders continue to haunt the global population. Several studies have suggested the role of specific environmental and genetic risk factors associated with these disorders. However, the exact mechanism associated with the progression of these disorders still needs to be elucidated. In the recent years, sophisticated research has revealed interesting association of prominent neurodegenerative disorders such as AD and PD with chronic diseases such as cancer, diabetes, and cardiovascular diseases. Several common molecular mechanisms such as generation of free radicals, oxidative DNA damage, aberrations in mitochondrial DNA, and dysregulation of apoptosis have been highlighted as possible points of connection. The present review summarizes the possible mechanism of coexistence of AD and PD with other chronic diseases.     

Zebrafish as a model for investigating developmental lead (Pb) neurotoxicity as a risk factor in adult neurodegenerative disease: A mini-review

Lead (Pb) exposure has long been recognized to cause neurological alterations in both adults and children. While most of the studies in adults are related to higher dose exposure, epidemiological studies indicate cognitive decline and neurobehavioral alterations in children associated with lower dose environmental Pb exposure (a blood Pb level of 10 μg/dL and below). Recent animal studies also now report that an early-life Pb exposure results in pathological hallmarks of Alzheimer's disease later in life. While previous studies evaluating higher Pb exposures in adult animal models and higher occupational Pb exposures in humans have suggested a link between higher dose Pb exposure during adulthood and neurodegenerative disease, these newer studies now indicate a link between an early-life Pb exposure and adult neurodegenerative disease. These studies are supporting the “fetal/developmental origin of adult disease” hypothesis and present a new challenge in our understanding of Pb neurotoxicity. There is a need to expand research in this area and additional model systems are needed. The zebrafish presents as a complementary vertebrate model system with numerous strengths including high genetic homology. Several zebrafish genes orthologous to human genes associated with neurodegenerative diseases including Alzheimer's and Parkinson's diseases are identified and this model is starting to be applied in neurodegenerative disease research. Moreover, the zebrafish is being used in developmental Pb neurotoxicity studies to define genetic mechanisms of toxicity and associated neurobehavioral alterations. While these studies are in their infancy, the genetic and functional conservation of genes associated with neurodegenerative diseases and application in developmental Pb neurotoxicity studies supports the potential for this in vivo model to further investigate the link between developmental Pb exposure and adult neurodegenerative disease pathogenesis. In this review, the major factors influencing the pathogenesis of neurodegenerative diseases, Pb neurotoxicity, the developmental origin of adult disease paradigm, and the zebrafish as a model system to investigate the developmental origin of low-dose Pb-induced neurodegenerative diseases is discussed.     

Choroid plexus function in neurological homeostasis and disorders: The awakening of the circadian clocks and orexins

As research regarding the role of circadian rhythms, sleep, and the orexinergic system in neurodegenerative diseases is growing, it is surprising that the choroid plexus (CP) remains underappreciated in this realm. Despite its extensive role in the regulation of circadian rhythms and orexinergic signalling, as well as acting as the primary conduit between cerebrospinal fluid (CSF) and the circulatory system, providing a mechanism by which toxic waste molecules can be removed from the brain, the CP has been largely unexplored in neurodegeneration. In this review, we explore the role of the CP in maintaining brain homeostasis and circadian rhythms, regulating CSF dynamics, and how these functions change across the lifespan, from development to senescence. In addition, we examine the relationship between the CP, orexinergic signalling, and the glymphatic system, highlighting gaps in the literature and areas that require immediate exploration. Finally, we assess current knowledge, including possible therapeutic strategies, regarding the role of the CP in neurological disorders, such as traumatic brain injury, migraine, Alzheimer’s disease, and multiple sclerosis.