Hasil untuk "Neurology. Diseases of the nervous system"

Melanie D. Sweeney, Zhen Zhao, Axel Montagne et al.

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of the central nervous system (CNS), which maintains tightly controlled chemical composition of the neuronal milieu that is required for proper neuronal functioning. In this review, we first examine molecular and cellular mechanisms underlying the establishment of the BBB. Then, we focus on BBB transport physiology, endothelial and pericyte transporters, and perivascular and paravascular transport. Next, we discuss rare human monogenic neurological disorders with the primary genetic defect in BBB-associated cells demonstrating the link between BBB breakdown and neurodegeneration. Then, we review the effects of genes underlying inheritance and/or increased susceptibility for Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and amyotrophic lateral sclerosis (ALS) on BBB in relation to other pathologies and neurological deficits. We next examine how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders such as stroke, traumatic brain injury, spinal cord injury, and epilepsy. Lastly, we discuss BBB-based therapeutic opportunities. We conclude with lessons learned and future directions, with emphasis on technological advances to investigate the BBB functions in the living human brain, and at the molecular and cellular level, and address key unanswered questions.

Sandro Da Mesquita, A. Louveau, Andrea Vaccari et al.

Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer’s disease promotes amyloid-β deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-β accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer’s disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases.Meningeal lymphatic dysfunction promotes amyloid-β deposition in the meninges and worsens brain amyloid-β pathology, acting as an aggravating factor in Alzheimer’s disease and in age-associated cognitive decline; improving meningeal lymphatic function could help to prevent or delay age-associated neurological diseases.

Clair R Martin, V. Osadchiy, A. Kalani et al.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.

K. Jomová, M. Maková, S. Alomar et al.

In total, twenty elements appear to be essential for the correct functioning of the human body, half of which are metals and half are non-metals. Among those metals that are currently considered to be essential for normal biological functioning are four main group elements, sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca), and six d-block transition metal elements, manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn) and molybdenum (Mo). Cells have developed various metallo-regulatory mechanisms for maintaining a necessary homeostasis of metal-ions for diverse cellular processes, most importantly in the central nervous system. Since redox active transition metals (for example Fe and Cu) may participate in electron transfer reactions, their homeostasis must be carefully controlled. The catalytic behaviour of redox metals which have escaped control, e.g. via the Fenton reaction, results in the formation of reactive hydroxyl radicals, which may cause damage to DNA, proteins and membranes. Transition metals are integral parts of the active centres of numerous enzymes (e.Dg. Cu,Zn-SOD, Mn-SOD, Catalase) which catalyze chemical reactions at physiologically compatible rates. Either a deficiency, or an excess of essential metals may result in various disease states arising in an organism. Some typical ailments that are characterized by a disturbed homeostasis of redox active metals include neurological disorders (Alzheimer's, Parkinson's and Huntington's disorders), mental health problems, cardiovascular diseases, cancer, and diabetes. To comprehend more deeply the mechanisms by which essential metals, acting either alone or in combination, and/or through their interaction with non-essential metals (e.g. chromium) function in biological systems will require the application of a broader, more interdisciplinary approach than has mainly been used so far. It is clear that a stronger cooperation between bioinorganic chemists and biophysicists - who have already achieved great success in understanding the structure and role of metalloenzymes in living systems - with biologists, will access new avenues of research in the systems biology of metal ions. With this in mind, the present paper reviews selected chemical and biological aspects of metal ions and their possible interactions in living systems under normal and pathological conditions.

A. Varatharaj, Ian Galea

The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. BBB changes occur in several CNS pathologies. Here, we review disruptive and non-disruptive BBB changes in systemic infections and other forms of systemic inflammation, and how these changes may affect CNS function in health and disease. We first describe the structure and function of the BBB, and outline the techniques used to study the BBB in vitro, and in animal and human settings. We then summarise the evidence from a range of models linking BBB changes with systemic inflammation, and the underlying mechanisms. The clinical relevance of these BBB changes during systemic inflammation are discussed in the context of clinically-apparent syndromes such as sickness behaviour, delirium, and septic encephalopathy, as well as neurological conditions such as Alzheimer's disease and multiple sclerosis. We review emerging evidence for two novel concepts: (1) a heightened sensitivity of the diseased, versus healthy, BBB to systemic inflammation, and (2) the contribution of BBB changes induced by systemic inflammation to progression of the primary disease process.

Yijing Chen, Jinying Xu, Yu Chen

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota–gut–brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.

L. Luo

C. Eroglu, B. Barres

A. Javed, O. Khan

Acute disseminated encephalomyelitis (ADEM) is an acute multifocal demyelinating disease of the central nervous system that typically follows an infectious illness. Its clinical course in most cases is monophasic; however, relapsing ADEM is rarely seen, which poses a diagnostic challenge for distinguishing this disease from multiple sclerosis (MS). Although typically encountered in children, it also occurs in adults with disease characteristics slightly different from the pediatric cases. Formerly, ADEM occurred particularly often in children with measles. However, the illness most often follows a non-descript viral or even bacterial infectious illness. ADEM occurs throughout the world, and may even be more common in less-developed countries, where MS is rare, than in developed ones, where MS is common. Children seldom get MS as opposed to adults, indicating that ADEM constitutes a distinct entity from MS. The prognosis of ADEM is generally good, but severe neurologic sequelae after ADEM are occasionally seen. In this chapter, the etiology, clinical/laboratory/radiologic characteristics, treatment options, and prognosis of ADEM are discussed.

F. Gage, S. Temple

Hanif Ullah, S. Arbab, Yali Tian et al.

The gut microbiota (GM) plays an important role in the physiology and pathology of the host. Microbiota communicate with different organs of the organism by synthesizing hormones and regulating body activity. The interaction of the central nervous system (CNS) and gut signaling pathways includes chemical, neural immune and endocrine routes. Alteration or dysbiosis in the gut microbiota leads to different gastrointestinal tract disorders that ultimately impact host physiology because of the abnormal microbial metabolites that stimulate and trigger different physiologic reactions in the host body. Intestinal dysbiosis leads to a change in the bidirectional relationship between the CNS and GM, which is linked to the pathogenesis of neurodevelopmental and neurological disorders. Increasing preclinical and clinical studies/evidence indicate that gut microbes are a possible susceptibility factor for the progression of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and autism spectrum disorder (ASD). In this review, we discuss the crucial connection between the gut microbiota and the central nervous system, the signaling pathways of multiple biological systems and the contribution of gut microbiota-related neurological disorders.

J. Sleigh, A. Rossor, Alexander D Fellows et al.

Benjamin E. Deverman, B. Ravina, K. Bankiewicz et al.

Neal D. Amin, S. Pașca

Disorders of the nervous system are challenging to study and treat due to the relative inaccessibility of functional human brain tissue for research. Stem cell-derived 3D human brain organoids have the potential to recapitulate features of the human brain with greater complexity than 2D models and are increasingly being applied to model diseases affecting the central nervous system. Here, we review the use of human brain organoids to investigate neurological and psychiatric (neuropsychiatric) disorders and how this technology may ultimately advance our biological understanding of these conditions.

C. Hassett, Aron Gedansky, I. Migdady et al.

Patients with COVID-19 have a fairly high risk of neurologic complications, including encephalopathy, stroke, central nervous system infection, seizures, and neuromuscular diseases. Many report losing their senses of smell and taste, and many survivors report lingering neurocognitive impairment. The diagnosis and treatment of these complications does not differ from that in other patients, although sophisticated testing may not be readily available for a patient in intensive care and respiratory isolation. Clinicians should therefore be alert to these complications. Human coronaviruses, including SARS-CoV-2, can be neurotropic.

Katarzyna Lepeta, Mychael V. Lourenco, Barbara Schweitzer et al.

Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions. Thus, optimal synaptic communication is required for proper brain physiology, and slight perturbations of synapse function can lead to brain disorders. In fact, increasing evidence has demonstrated the relevance of synapse dysfunction as a major determinant of many neurological diseases. This notion has led to the concept of synaptopathies as brain diseases with synapse defects as shared pathogenic features. In this review, which was initiated at the 13th International Society for Neurochemistry Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental disorders (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer and Parkinson disease). We finally discuss the appropriateness and potential implications of gathering synapse diseases under a single term. Understanding common causes and intrinsic differences in disease‐associated synaptic dysfunction could offer novel clues toward synapse‐based therapeutic intervention for neurological and neuropsychiatric disorders.

E. Balcom, A. Nath, C. Power

Abstract Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain–Barré syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of CSF and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischaemic injury, blood–brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development and uncovering the underlying disease mechanisms that will guide effective therapies.

Nur Fadhilah Umar, M. Fiqri Syahril, Salsabila Nasution et al.

Ego identity plays a crucial role in shaping an individual’s self-concept, career decisions, and social relationships. Accurately measuring ego identity status is essential for understanding identity formation and promoting healthy psychological development. This study examines the validity and reliability of the adapted Objective Measure of Ego Identity Status (OMEIS) using the Rasch Model, a contemporary psychometric approach that enhances measurement precision. A sample of 431 university students participated in this study, with data collected through an online questionnaire. Rasch analysis was employed to assess item fit, rating scale effectiveness, person reliability, and item difficulty levels. The results indicate that the adapted OMEIS demonstrates strong structural validity and high item reliability (0.99), although person reliability (0.63) requires improvement. The Wright Map analysis confirms the instrument’s ability to capture variations in ego identity, while item difficulty analysis highlights areas for potential refinement. Findings suggest that the Rasch Model provides a robust framework for validating psychological instruments, ensuring their applicability across diverse populations. This study contributes to the refinement of identity measurement tools and underscores the importance of advanced psychometric methodologies in psychological research

Myriam V. Thoma, Enya Redican, Nathanael Adank et al.

Background: This study assessed the prevalence rates, construct validity, predictors, and psychosocial factors linked to ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD), as assessed by the International Trauma Questionnaire (ITQ) in a German-speaking sample of Swiss older adults.Method: Participants were N = 1526 older adults aged 65+ (Mage = 72.34; SD = 6.20 years; age range = 65–95; female = 72.0%). Confirmatory factor analysis (CFA) tested alternative models of the latent structure of the ITQ. Risk factors and psychological outcomes associated with the ITQ subscales were also examined.Results: From the total sample, 86.2% had experienced at least one potentially traumatic event (PTE), with a median of three PTEs per person. Probable PTSD and CPTSD prevalence was 0.4% and 2.4%, respectively. CFA results indicated that a two-factor second-order model best captured the latent structure of the ITQ. Female gender and specific traumas, such as physical and sexual assault, were uniquely associated with PTSD. Fewer, non-specific factors were linked to disturbances in self-organization (DSO; encompassing affective dysregulation, a negative self-view, and difficulties in relationships). The PTSD and CPTSD factors were significantly associated with loneliness, anxiety, depression, and well-being.Conclusions: Results found that despite high trauma exposure among Swiss older adults, the prevalence of ICD-11 PTSD and CPTSD was low, with no significant gender differences. A two-factor second-order model provided the best fit for the ITQ. These findings indicate significant trauma exposure in Swiss older adults and the need for targeted interventions that address the trauma-specific and associated psychosocial challenges (i.e. loneliness, anxiety, depression, well-being) facing older adults.

Jae Young Lee, Hee Jung Lee, Jun Chul Byun