Role of Brain Iron Accumulation in Cognitive Dysfunction: Evidence from Animal Models and Human Studies

2013 ◽  
Vol 34 (4) ◽  
pp. 797-812 ◽  
Author(s):  
Nadja Schröder ◽  
Luciana Silva Figueiredo ◽  
Maria Noêmia Martins de Lima
Keyword(s):  
Animal Models ◽  
Cognitive Dysfunction ◽  
Human Studies ◽  
Iron Accumulation ◽  
Brain Iron

scholarly journals Postnatal Role of the Cytoskeleton in Adult Epileptogenesis

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Cezar Gavrilovici ◽  
Yulan Jiang ◽  
Ivana Kiroski ◽  
G Campbell Teskey ◽  
Jong M Rho ◽  
...  
Keyword(s):  
Animal Models ◽  
Neuronal Activity ◽  
Causative Factor ◽  
Cytoskeletal Proteins ◽  
Human Studies ◽  
Pathogenic Mechanism ◽  
Neuronal Connectivity ◽  
Cytoskeletal Disruption

Abstract Mutations in cytoskeletal proteins can cause early infantile and childhood epilepsies by misplacing newly born neurons and altering neuronal connectivity. In the adult epileptic brain, cytoskeletal disruption is often viewed as being secondary to aberrant neuronal activity and/or death, and hence simply represents an epiphenomenon. Here, we review the emerging evidence collected in animal models and human studies implicating the cytoskeleton as a potential causative factor in adult epileptogenesis. Based on the emerging evidence, we propose that cytoskeletal disruption may be an important pathogenic mechanism in the mature epileptic brain.

scholarly journals Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit

2021 ◽  
Vol 15 ◽  
Author(s):  
Ashley D. Turner ◽  
Travis Sullivan ◽  
Kurt Drury ◽  
Trevor A. Hall ◽  
Cydni N. Williams ◽  
...  
Keyword(s):  
Intensive Care ◽  
Critical Illness ◽  
Animal Models ◽  
Critically Ill ◽  
Cognitive Dysfunction ◽  
Functional Outcomes ◽  
Pediatric Intensive Care ◽  
Critically Ill Children ◽  
Post Discharge

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately “reverse translate” critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care.

Role of 18F-FDG PET imaging in paediatric primary dystonia and dystonia arising from neurodegeneration with brain iron accumulation

2015 ◽  
Vol 36 (5) ◽  
pp. 469-476 ◽  
Author(s):  
Teresa A. Szyszko ◽  
Joel T. Dunn ◽  
Michael J. O’Doherty ◽  
Laurence Reed ◽  
Jean-Pierre Lin
Keyword(s):  
Pet Imaging ◽  
Fdg Pet ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Primary Dystonia ◽  
18F Fdg

scholarly journals Iron and Neurodegeneration in Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Michael Khalil ◽  
Charlotte Teunissen ◽  
Christian Langkammer
Keyword(s):  
Multiple Sclerosis ◽  
Iron Homeostasis ◽  
Venous Insufficiency ◽  
Quantitative Mri ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Etiologic Role ◽  
Quantitative Manner ◽  
Related Proteins

Increased iron deposition might be implicated in multiple sclerosis (MS). Recent development of MRI enabled to determine brain iron levels in a quantitative manner, which has put more interest on studying the role of iron in MS. Evidence for abnormal iron homeostasis in MS comes also from analyses of iron and iron-related proteins in CSF and blood and postmortem MS brain sections. However, it is not yet clear if iron accumulation is implicated in MS pathology or merely reflects an epiphenomenon. Further interest has been generated by the idea of chronic cerebrospinal venous insufficiency that might be associated with brain iron accumulation due to a reduction in venous outflow, but its existence and etiologic role in MS are currently controversially debated. In future studies, combined approaches applying quantitative MRI together with CSF and serum analyses of iron and iron-related proteins in a clinical followup setting might help to elucidate the implication of iron accumulation in MS.

Role of dendritic cells in the lung:in vitromodels, animal models and human studies

2008 ◽  
Vol 2 (2) ◽  
pp. 215-233 ◽  
Author(s):  
Fabian Blank ◽  
Christophe von Garnier ◽  
Carolina Obregon ◽  
Barbara Rothen-Rutishauser ◽  
Peter Gehr ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Animal Models ◽  
Human Studies

scholarly journals Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Vassilena Iankova ◽  
Ivan Karin ◽  
Thomas Klopstock ◽  
Susanne A. Schneider
Keyword(s):  
Animal Models ◽  
Wide Spectrum ◽  
Controlled Trial ◽  
Speech Disorders ◽  
New Drugs ◽  
Iron Accumulation ◽  
Neuroaxonal Dystrophy ◽  
Brain Iron ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogeneous group of progressive neurodegenerative diseases characterized by iron deposition in the globus pallidus and the substantia nigra. As of today, 15 distinct monogenetic disease entities have been identified. The four most common forms are pantothenate kinase-associated neurodegeneration (PKAN), phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN), beta-propeller protein-associated neurodegeneration (BPAN) and mitochondrial membrane protein-associated neurodegeneration (MPAN). Neurodegeneration with Brain Iron Accumulation disorders present with a wide spectrum of clinical symptoms such as movement disorder signs (dystonia, parkinsonism, chorea), pyramidal involvement (e.g., spasticity), speech disorders, cognitive decline, psychomotor retardation, and ocular abnormalities. Treatment remains largely symptomatic but new drugs are in the pipeline. In this review, we discuss the rationale of new compounds, summarize results from clinical trials, provide an overview of important results in cell lines and animal models and discuss the future development of disease-modifying therapies for NBIA disorders. A general mechanistic approach for treatment of NBIA disorders is with iron chelators which bind and remove iron. Few studies investigated the effect of deferiprone in PKAN, including a recent placebo-controlled double-blind multicenter trial, demonstrating radiological improvement with reduction of iron load in the basal ganglia and a trend to slowing of disease progression. Disease-modifying strategies address the specific metabolic pathways of the affected enzyme. Such tailor-made approaches include provision of an alternative substrate (e.g., fosmetpantotenate or 4′-phosphopantetheine for PKAN) in order to bypass the defective enzyme. A recent randomized controlled trial of fosmetpantotenate, however, did not show any significant benefit of the drug as compared to placebo, leading to early termination of the trials' extension phase. 4′-phosphopantetheine showed promising results in animal models and a clinical study in patients is currently underway. Another approach is the activation of other enzyme isoforms using small molecules (e.g., PZ-2891 in PKAN). There are also compounds which counteract downstream cellular effects. For example, deuterated polyunsaturated fatty acids (D-PUFA) may reduce mitochondrial lipid peroxidation in PLAN. In infantile neuroaxonal dystrophy (a subtype of PLAN), desipramine may be repurposed as it blocks ceramide accumulation. Gene replacement therapy is still in a preclinical stage.

Neurodegeneration with brain iron accumulation type 4 by mutation in the C19orf12 gene: first time found in adolescent of Russian origin

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
E Giagkou ◽  
S Lutz ◽  
U Schara ◽  
K Becker ◽  
C Möller-Hartmann
Keyword(s):  
Iron Accumulation ◽  
Brain Iron ◽  
First Time

Psychotic Disorder in Neurodegeneration with Brain Iron Accumulation

2016 ◽  
Vol 10 (3) ◽  
pp. 178-180
Author(s):  
Menekse Sila Yazar ◽  
Nurhan Fistikci ◽  
Ozlem Devrim Balaban ◽  
Nezih Eradamlar ◽  
Latif Alpkan
Keyword(s):  
Psychotic Disorder ◽  
Iron Accumulation ◽  
Brain Iron
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