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Neurol. Int., Volume 15, Issue 3 (September 2023) – 27 articles

Cover Story (view full-size image): Long-COVID has been a major consequence of the COVID-19 pandemic and continues to be a worldwide health concern. In particular, neurologic symptoms that linger beyond the acute phase of the disease can cause drastic negative effects on a patient’s ability to function and quality of life. Among the major central nervous system clinical manifestations of long-COVID are brain fog, headache, sleep disturbances, fatigue and depression. Sensorimotor symptoms experienced beyond 12 weeks after initial COVID-19 infection include neuropathic pain, myalgias and muscle weakness. Proposed pathological mechanisms underlying these symptoms generally focus on neuroinflammatory and systemic inflammatory processes, immune dysregulation and cerebral metabolic dysfunction. Treatment options are limited and a focus of intensive research. View this paper
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9 pages, 2897 KiB  
Case Report
Treatment of Acute Ischaemic Stroke and Concomitant Multiple Arterial Splanchnic Thromboses in a Patient with Immune Thrombocytopenia on Thrombopoietin Agonist: A Case Report
Neurol. Int. 2023, 15(3), 1191-1199; https://doi.org/10.3390/neurolint15030074 - 18 Sep 2023
Viewed by 875
Abstract
Immune thrombocytopenia (ITP) is an autoimmune blood disorder characterised by isolated severe thrombocytopenia. Arterial thrombotic events, such as acute ischaemic stroke (AIS), are rare complications. A 56-year-old woman with chronic ITP on eltrombopag and dexamethasone therapy presented to the emergency department due to [...] Read more.
Immune thrombocytopenia (ITP) is an autoimmune blood disorder characterised by isolated severe thrombocytopenia. Arterial thrombotic events, such as acute ischaemic stroke (AIS), are rare complications. A 56-year-old woman with chronic ITP on eltrombopag and dexamethasone therapy presented to the emergency department due to AIS in the vertebrobasilar territory, and lower abdominal pain. The computed tomography (CT) scan of the head was unremarkable, whereas CT angiography revealed left vertebral artery occlusion. As the platelet count was sufficient, intravenous thrombolysis (IVT) was initiated. However, after 15 min, an anaphylactic reaction occurred, which was appropriately solved. Although the IVT was prematurely stopped, the NIHSS score improved from 7 to 2, and the follow-up head CT scan remained unremarkable. CT angiography of the thoracoabdominal aorta revealed multiple thrombi in the infrarenal aorta, inferior mesenteric artery (IMA), and left renal artery. The abdominal pain subsided after IVT, but recurred within 24 h. Repeated CT angiography showed ischaemia of the descending colon, with persistent IMA occlusion. After the hemicolectomy condition stabilised. Discrete left-sided ataxia and impaired sensation were the only neurological sequelae. We found two articles reporting only three patients with ITP who suffered AIS and were treated with IVT. A favourable outcome was observed in two cases, while one patient suffered an intracranial haemorrhage (ICH) and died. A review of AIS cases with undefined thrombocytopenia treated with IVT reported ICH in up to 6.8% of patients. Our case suggests that IVT for AIS may be effective in patients with ITP. Further data are needed to better clarify this issue. Full article
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17 pages, 2525 KiB  
Review
All Roads Lead to the Gut: The Importance of the Microbiota and Diet in Migraine
Neurol. Int. 2023, 15(3), 1174-1190; https://doi.org/10.3390/neurolint15030073 - 13 Sep 2023
Viewed by 1096
Abstract
Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of [...] Read more.
Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of the trigeminal system are crucial during migraine attacks, and specific substances have been recognized for their distinct involvement in the pathomechanism of migraine. Recently, an expanding body of data indicates that migraine attacks can be prevented and treated through dietary means. It is important to highlight that the various diets available pose risks for patients without professional guidance. This comprehensive overview explores the connection between migraine, the gut microbiome, and gastrointestinal disorders. It provides insight into migraine-triggering foods, and discusses potential diets to help reduce the frequency and severity of migraine attacks. Additionally, it delves into the benefits of using pre- and probiotics as adjunctive therapy in migraine treatment. Full article
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19 pages, 2565 KiB  
Review
Molecular Pathogenic Mechanisms of Hypomyelinating Leukodystrophies (HLDs)
Neurol. Int. 2023, 15(3), 1155-1173; https://doi.org/10.3390/neurolint15030072 - 11 Sep 2023
Viewed by 861
Abstract
Hypomyelinating leukodystrophies (HLDs) represent a group of congenital rare diseases for which the responsible genes have been identified in recent studies. In this review, we briefly describe the genetic/molecular mechanisms underlying the pathogenesis of HLD and the normal cellular functions of the related [...] Read more.
Hypomyelinating leukodystrophies (HLDs) represent a group of congenital rare diseases for which the responsible genes have been identified in recent studies. In this review, we briefly describe the genetic/molecular mechanisms underlying the pathogenesis of HLD and the normal cellular functions of the related genes and proteins. An increasing number of studies have reported genetic mutations that cause protein misfolding, protein dysfunction, and/or mislocalization associated with HLD. Insight into the mechanisms of these pathways can provide new findings for the clinical treatments of HLD. Full article
(This article belongs to the Special Issue Review Papers in Genetic Neuropathies 2023)
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15 pages, 512 KiB  
Systematic Review
Altered Cardiac Autonomic Regulation in Individuals with Myasthenia Gravis—A Systematic Review and Meta-Analysis
Neurol. Int. 2023, 15(3), 1140-1154; https://doi.org/10.3390/neurolint15030071 - 08 Sep 2023
Cited by 1 | Viewed by 1105
Abstract
The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception [...] Read more.
The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception to 7 July 2023 for studies investigating cardiovascular autonomic parameters in MG vs. HCs. A random-effects meta-analysis was performed to compute Hedges’ g ± 95% confidence intervals (CI). Out of a total of 2200 records, 8 observational studies with a sample size of 301 patients with MG and 454 HCs were included in the systematic review. Meta-analysis revealed lower values of expiration/inspiration ratio (g = −0.45, I2 = 74.7), baroreflex sensitivity (g = −0.56, 95%CI −0.80, −0.33; I2 = 0.3), percentage of adjacent NN intervals differing by more than 50 ms (g = −1.2, I2 = 82.8), square root of the mean of squared differences between successive beat intervals (g = −1.94, I2 = 95.1), mean of the standard deviations of all NN intervals (g = −0.83, 95%CI −1.37, −0.28; I2 = 55.5), and high frequency of HRV during tilt (g = −0.75, 95%CI −0.11, −0.39; I2 = 0). MG patients vs. HCs had higher systolic blood pressure (g = 0.39; I2 = 56.1), sympathovagal balance at rest/during tilt (LF/HF-RRIsupine, g = 0.44; I2 = 0; LF/HF-RRItilt, g = 0.86; I2 = 0; LF/HFtilt, g = 0.40; I2 = 0). As a group, MG patients have altered cardiac autonomic function, including decreased parasympathetic function, lower baroreflex sensitivity, and higher sympathovagal balance at rest and during orthostatic challenges. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis, Volume II)
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11 pages, 1194 KiB  
Article
A Comparative Analysis of Symmetry Indices for Spatiotemporal Gait Features in Early Parkinson’s Disease
Neurol. Int. 2023, 15(3), 1129-1139; https://doi.org/10.3390/neurolint15030070 - 07 Sep 2023
Viewed by 689
Abstract
This study compared the five most commonly used equations for calculating gait symmetry in discrete variables among Parkinson’s disease patients. Twelve patients (five women and seven men) performed ten consecutive gait trials on a 10 m walkway. Gait data were collected using eight [...] Read more.
This study compared the five most commonly used equations for calculating gait symmetry in discrete variables among Parkinson’s disease patients. Twelve patients (five women and seven men) performed ten consecutive gait trials on a 10 m walkway. Gait data were collected using eight optoelectronic cameras (100 fr/s). The analysis focused on various spatiotemporal parameters, including cadence, step time, stride time, single support, double support, walking speed, step length, stride length, step width, and foot angle. Five symmetry indices were calculated for each trial rather than averaging the ten recorded trials. The variability in and reliability of each symmetry equation were assessed using the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. Additionally, Bland–Altman plots were produced to visualize the agreement between each pair of methods for each spatiotemporal parameter. The results revealed that the symmetry ratio method exhibited lower variability and higher reliability compared with the other four indices across all spatiotemporal gait parameters. However, it was found that the reliability of a single trial was generally poor, regardless of the symmetry calculation formula used. Therefore, we recommend basing measurements of gait asymmetry in Parkinson’s disease on multiple trials. Full article
(This article belongs to the Collection Advances in Neurodegenerative Diseases)
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12 pages, 311 KiB  
Article
Genetic Variability in Vitamin D Receptor and Migraine Susceptibility: A Southeastern European Case-Control Study
Neurol. Int. 2023, 15(3), 1117-1128; https://doi.org/10.3390/neurolint15030069 - 05 Sep 2023
Viewed by 732
Abstract
Migraine is a common primary headache disorder with both environmental and genetic inputs. Cumulative evidence indicates an association between vitamin D and headache. Unravelling the precise role of vitamin D and its receptor in the pathophysiology of migraine can eventually contribute to more [...] Read more.
Migraine is a common primary headache disorder with both environmental and genetic inputs. Cumulative evidence indicates an association between vitamin D and headache. Unravelling the precise role of vitamin D and its receptor in the pathophysiology of migraine can eventually contribute to more efficient prevention and management of this headache disorder. The aim of the study was to investigate the relation of the three most studied VDR variants, i.e., FokI (rs2228570), TaqI (rs731236) and BsmI (rs1544410), with migraine susceptibility and distinct clinical phenotypes in a Southeastern European case-control population residing in Greece. DNA was extracted from 191 unrelated patients diagnosed with migraine and 265 headache-free controls and genotyped using real-time PCR (LightSNiP assays) followed by melting curve analysis. Genotype frequency distribution analysis of the TaqI and BsmI variants showed a statistically significant difference between migraine cases and controls. In addition, subgroup analyses revealed a significant association between all three studied VDR variants, particularly with a migraine without aura subtype. Therefore, the current study provides supporting evidence for a possible association of VDR variants with migraines, particularly migraine without aura susceptibility in Southeastern Europeans residing in Greece, further reinforcing the emerging role of vitamin D and its receptor in migraines. Full article
11 pages, 341 KiB  
Protocol
Social Cognition Impairments in Association to Clinical, Cognitive, Mood, and Fatigue Features in Multiple Sclerosis: A Study Protocol
Neurol. Int. 2023, 15(3), 1106-1116; https://doi.org/10.3390/neurolint15030068 - 01 Sep 2023
Viewed by 670
Abstract
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS), characterized by the diffuse grey and white matter damage. Cognitive impairment (CI) is a frequent clinical feature in patients with MS (PwMS) that can be prevalent even in early [...] Read more.
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS), characterized by the diffuse grey and white matter damage. Cognitive impairment (CI) is a frequent clinical feature in patients with MS (PwMS) that can be prevalent even in early disease stages, affecting the physical activity and active social participation of PwMS. Limited information is available regarding the influence of MS in social cognition (SC), which may occur independently from the overall neurocognitive dysfunction. In addition, the available information regarding the factors that influence SC in PwMS is limited, e.g., factors such as a patient’s physical disability, different cognitive phenotypes, mood status, fatigue. Considering that SC is an important domain of CI in MS and may contribute to subjects’ social participation and quality of life, we herein conceptualize and present the methodological design of a cross-sectional study in 100 PwMS of different disease subtypes. The study aims (a) to characterize SC impairment in PwMS in the Greek population and (b) to unveil the relationship between clinical symptoms, phenotypes of CI, mood status and fatigue in PwMS and the potential underlying impairment on tasks of SC. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis, Volume II)
54 pages, 3017 KiB  
Review
Migraine: Advances in the Pathogenesis and Treatment
Neurol. Int. 2023, 15(3), 1052-1105; https://doi.org/10.3390/neurolint15030067 - 31 Aug 2023
Viewed by 4542
Abstract
This article presents a comprehensive review on migraine, a prevalent neurological disorder characterized by chronic headaches, by focusing on their pathogenesis and treatment advances. By examining molecular markers and leveraging imaging techniques, the research identifies key mechanisms and triggers in migraine pathology, thereby [...] Read more.
This article presents a comprehensive review on migraine, a prevalent neurological disorder characterized by chronic headaches, by focusing on their pathogenesis and treatment advances. By examining molecular markers and leveraging imaging techniques, the research identifies key mechanisms and triggers in migraine pathology, thereby improving our understanding of its pathophysiology. Special emphasis is given to the role of calcitonin gene-related peptide (CGRP) in migraine development. CGRP not only contributes to symptoms but also represents a promising therapeutic target, with inhibitors showing effectiveness in migraine management. The article further explores traditional medical treatments, scrutinizing the mechanisms, benefits, and limitations of commonly prescribed medications. This provides a segue into an analysis of emerging therapeutic strategies and their potential to enhance migraine management. Finally, the paper delves into neuromodulation as an innovative treatment modality. Clinical studies indicating its effectiveness in migraine management are reviewed, and the advantages and limitations of this technique are discussed. In summary, the article aims to enhance the understanding of migraine pathogenesis and present novel therapeutic possibilities that could revolutionize patient care. Full article
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8 pages, 2704 KiB  
Brief Report
Serum GDF-15 Levels in Patients with Parkinson’s Disease, Progressive Supranuclear Palsy, and Multiple System Atrophy
Neurol. Int. 2023, 15(3), 1044-1051; https://doi.org/10.3390/neurolint15030066 - 30 Aug 2023
Viewed by 684
Abstract
Serum growth differentiation factor 15 (GDF-15) levels are elevated in patients with Parkinson’s disease (PD) and may help differentiate these patients from healthy individuals. We aimed to clarify whether serum GDF-15 levels can help differentiate PD from atypical parkinsonian syndromes and determine the [...] Read more.
Serum growth differentiation factor 15 (GDF-15) levels are elevated in patients with Parkinson’s disease (PD) and may help differentiate these patients from healthy individuals. We aimed to clarify whether serum GDF-15 levels can help differentiate PD from atypical parkinsonian syndromes and determine the association between serum GDF-15 levels and clinical parameters. We prospectively enrolled 46, 15, and 12 patients with PD, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA), respectively. The serum GDF-15 level in patients with PD (1394.67 ± 558.46 pg/mL) did not differ significantly from that in patients with PSP (1491.27 ± 620.78 pg/mL; p = 0.573) but was significantly higher than that in patients with MSA (978.42 ± 334.66 pg/mL; p = 0.017). Serum GDF-15 levels were positively correlated with age in patients with PD (r = 0.458; p = 0.001); PSP (r = 0.565; p = 0.028); and MSA (r = 0.708; p = 0.010). After accounting for age differences, serum GDF-15 levels did not differ significantly between patients with PD and MSA (p = 0.114). Thus, age has a strong influence on serum GDF-15 levels, which may not differ significantly between patients with PD and atypical parkinsonian syndromes such as PSP and MSA. Full article
(This article belongs to the Collection Advances in Neurodegenerative Diseases)
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30 pages, 4026 KiB  
Article
Atrial Fibrillation and Reperfusion Therapy in Acute Ischaemic Stroke Patients: Prevalence and Outcomes—A Comprehensive Systematic Review and Meta-Analysis
Neurol. Int. 2023, 15(3), 1014-1043; https://doi.org/10.3390/neurolint15030065 - 25 Aug 2023
Cited by 1 | Viewed by 789
Abstract
Atrial fibrillation (AF) significantly contributes to acute ischaemic stroke (AIS), yet its precise influence on clinical outcomes post-intravenous thrombolysis (IVT) and post-endovascular thrombectomy (EVT) has remained elusive. Furthermore, the overall prevalence of AF in AIS patients undergoing reperfusion therapy has not been clearly [...] Read more.
Atrial fibrillation (AF) significantly contributes to acute ischaemic stroke (AIS), yet its precise influence on clinical outcomes post-intravenous thrombolysis (IVT) and post-endovascular thrombectomy (EVT) has remained elusive. Furthermore, the overall prevalence of AF in AIS patients undergoing reperfusion therapy has not been clearly determined. Employing random-effects meta-analyses, this research aimed to estimate the pooled prevalence of AF among AIS patients undergoing reperfusion therapy, while also examining the association between AF and clinical outcomes such as functional outcomes, symptomatic intracerebral haemorrhage (sICH) and mortality. Studies comparing AF and non-AF patient groups undergoing reperfusion therapy were identified and included following an extensive database search. Forty-nine studies (n = 66,887) were included. Among IVT patients, the prevalence of AF was 31% (Effect Size [ES] 0.31 [95%CI 0.28–0.35], p < 0.01), while in EVT patients, it reached 42% (ES 0.42 [95%CI 0.38–0.46], p < 0.01), and in bridging therapy (BT) patients, it stood at 36% (ES 0.36 [95%CI 0.28–0.43], p < 0.01). AF was associated with significantly lower odds of favourable 90-day functional outcomes post IVT (Odds Ratio [OR] 0.512 [95%CI 0.376–0.696], p < 0.001), but not post EVT (OR 0.826 [95%CI 0.651–1.049], p = 0.117). Our comprehensive meta-analysis highlights the varying prevalence of AF among different reperfusion therapies and its differential impact on patient outcomes. The highest pooled prevalence of AF was observed in EVT patients, followed by BT and IVT patients. Interestingly, our analysis revealed that AF was significantly associated with poorer clinical outcomes following IVT. Such an association was not observed following EVT. Full article
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20 pages, 650 KiB  
Systematic Review
Leukoaraiosis as a Promising Biomarker of Stroke Recurrence among Stroke Survivors: A Systematic Review
Neurol. Int. 2023, 15(3), 994-1013; https://doi.org/10.3390/neurolint15030064 - 21 Aug 2023
Viewed by 721
Abstract
Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients’ quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely [...] Read more.
Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients’ quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely and reliable prognosis of stroke recurrence. Leukoaraiosis (LA) is a common neuroimaging feature of cerebral small-vessel disease. By researching the literature of two different databases (MEDLINE and Scopus), the present study aims to review all relevant studies from the last decade, dealing with the clinical utility of pre-existing LA as a prognostic factor for stroke recurrence in stroke survivors. Nineteen full-text articles published in English were identified and included in the present review, with data collected from a total of 34,546 stroke patients. A higher rate of extended LA was strongly associated with stroke recurrence in all stroke subtypes, even after adjustment for clinical risk factors. In particular, patients with ischemic stroke or transient ischemic attack with advanced LA had a significantly higher risk of future ischemic stroke, whereas patients with previous intracerebral hemorrhage and severe LA had a more than 2.5-fold increased risk of recurrent ischemic stroke and a more than 30-fold increased risk of hemorrhagic stroke. Finally, in patients receiving anticoagulant treatment for AF, the presence of LA was associated with an increased risk of recurrent ischemic stroke and intracranial hemorrhage. Because of this valuable predictive information, evaluating LA could significantly expand our knowledge of stroke patients and thereby improve overall stroke care. Full article
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14 pages, 3981 KiB  
Article
FTD/ALS Type 7-Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator
Neurol. Int. 2023, 15(3), 980-993; https://doi.org/10.3390/neurolint15030063 - 11 Aug 2023
Viewed by 1076
Abstract
Frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTD/ALS7) is an autosomal dominant neurodegenerative disorder characterized by the onset of FTD and/or ALS, mainly in adulthood. Patients with some types of mutations, including the Thr104Asn (T104N) mutation of charged multivesicular body protein 2B [...] Read more.
Frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTD/ALS7) is an autosomal dominant neurodegenerative disorder characterized by the onset of FTD and/or ALS, mainly in adulthood. Patients with some types of mutations, including the Thr104Asn (T104N) mutation of charged multivesicular body protein 2B (CHMP2B), have predominantly ALS phenotypes, whereas patients with other mutations have predominantly FTD phenotypes. A few mutations result in patients having both phenotypes approximately equally; however, the reason why phenotypes differ depending on the position of the mutation is unknown. CHMP2B comprises one part of the endosomal sorting complexes required for transport (ESCRT), specifically ESCRT-III, in the cytoplasm. We describe here, for the first time, that CHMP2B with the T104N mutation inhibits neuronal process elongation in the N1E-115 cell line, a model line undergoing neuronal differentiation. This inhibitory phenotype was accompanied by changes in marker protein expression. Of note, CHMP2B with the T104N mutation, but not the wild-type form, was preferentially accumulated in the Golgi body. Of the four major Golgi stress signaling pathways currently known, the pathway through Arf4, the small GTPase, was specifically upregulated in cells expressing CHMP2B with the T104N mutation. Conversely, knockdown of Arf4 with the cognate small interfering (si)RNA recovered the neuronal process elongation inhibited by the T104N mutation. These results suggest that the T104N mutation of CHMP2B inhibits morphological differentiation by triggering Golgi stress signaling, revealing a possible therapeutic molecular target for recovering potential molecular and cellular phenotypes underlying FTD/ALS7. Full article
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13 pages, 870 KiB  
Review
In Search of a Function for the N6-Methyladenosine in Epitranscriptome, Autophagy and Neurodegenerative Diseases
Neurol. Int. 2023, 15(3), 967-979; https://doi.org/10.3390/neurolint15030062 - 10 Aug 2023
Viewed by 1387
Abstract
Changes in epitranscriptome with N6-methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. [...] Read more.
Changes in epitranscriptome with N6-methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. Importantly, the m6A methylation may be associated with various neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, aging-related diseases, and/or aging itself. In addition, the m6A methylation might functionally regulate the eukaryotic transcriptome by influencing the splicing, export, subcellular localization, translation, stability, and decay of mRNAs. Neurodegenerative diseases may possess a wide variety of phenotypes, depending on the neurons that degenerate on occasion. Interestingly, an increasing amount of evidence has indicated that m6A modification could modulate the expression of autophagy-related genes and promote autophagy in neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) could stimulate the m6A RNA methylation, which may also be related to the regulation of autophagy and/or the development of neurodegenerative diseases. Both m6A modification and autophagy could also play critical roles in regulating the health condition of neurons. Therefore, a comprehensive understanding of the m6A and autophagy relationship in human diseases may benefit in developing therapeutic strategies in the future. This paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of neurodegenerative diseases and/or aging, discussing the possible therapeutic procedures related to mechanisms of m6A RNA methylation and autophagy. Full article
(This article belongs to the Collection Advances in Neurodegenerative Diseases)
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13 pages, 2841 KiB  
Article
Modified TPP-MoS2 QD Blend as a Bio-Functional Model for Normalizing Microglial Dysfunction in Alzheimer’s Disease
Neurol. Int. 2023, 15(3), 954-966; https://doi.org/10.3390/neurolint15030061 - 08 Aug 2023
Cited by 1 | Viewed by 906
Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of β-amyloid peptide (Aβ) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play [...] Read more.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of β-amyloid peptide (Aβ) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play an important role in maintaining brain homeostasis through a variety of phenotypes, including the pro-inflammatory phenotype and anti-inflammatory phenotypes. However, persistently activated microglial cells generate reactive species and neurotoxic mediators. Therefore, inhibitors of microglial activation are seen to have promise in AD control. The modified TPP/MoS2 QD blend is a mitochondrion-targeted nanomaterial that exhibits cytoprotective activities and antioxidant properties through scavenging free radicals. In the present study, the cell viability and cytotoxicity of the DSPE-PEG-TPP/MoS2 QD blend on microglial cells stimulated by Aβ were investigated. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also assessed. In addition, pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), transforming growth factor beta (TGF-β), inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-I) were measured in the presence or absence of the DSPE-PEG-TPP/MoS2 QD blend on an immortalized microglia cells activated by accumulation of Aβ. We found that the DSPE-PEG-TPP/MoS2 QD blend was biocompatible and nontoxic at specific concentrations. Furthermore, the modified TPP/MoS2 QD blend significantly reduced the release of free radicals and improved the mitochondrial function through the upregulation of MMP in a dose-dependent manner on microglial cells treated with Aβ. In addition, pre-treatment of microglia with the DSPE-PEG-TPP/MoS2 QD blend at concentrations of 25 and 50 μg/mL prior to Aβ stimulation significantly inhibited the release and expression of pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, and iNOS. Nevertheless, the anti-inflammatory cytokines TGF-β and Arg-I were activated. These findings suggest that the modified TPP/MoS2 QD blend reduced oxidative stress, inflammation and improved the mitochondrial function in the immortalized microglial cells (IMG) activated by Aβ. Overall, our research shows that the DSPE-PEG-TPP/MoS2 QD blend has therapeutic promise for managing AD and can impact microglia polarization. Full article
(This article belongs to the Collection Advances in Neurodegenerative Diseases)
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28 pages, 542 KiB  
Systematic Review
Investigating the Predictive Value of Thyroid Hormone Levels for Stroke Prognosis
Neurol. Int. 2023, 15(3), 926-953; https://doi.org/10.3390/neurolint15030060 - 02 Aug 2023
Viewed by 983
Abstract
Given the expansion of life expectancy, the aging of the population, and the anticipated rise in the number of stroke survivors in Europe with severe neurological consequences in the coming decades, stroke is becoming the most prevalent cause of functional disability. Therefore, the [...] Read more.
Given the expansion of life expectancy, the aging of the population, and the anticipated rise in the number of stroke survivors in Europe with severe neurological consequences in the coming decades, stroke is becoming the most prevalent cause of functional disability. Therefore, the prognosis for a stroke must be timely and precise. Two databases (MEDLINE and Scopus) were searched to identify all relevant studies published between 1 January 2005 and 31 December 2022 that investigated the relationship between thyroid hormone levels and acute stroke severity, mortality, and post-hospital prognosis. Only full-text English-language articles were included. This review includes Thirty articles that were traced and incorporated into the present review. Emerging data regarding the potential predictive value of thyroid hormone levels suggests there may be a correlation between low T3 syndrome, subclinical hypothyroidism, and poor stroke outcome, especially in certain age groups. These findings may prove useful for rehabilitation and therapy planning in clinical practice. Serum thyroid hormone concentration measurement is a non-invasive, relatively harmless, and secure screening test that may be useful for this purpose. Full article
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9 pages, 1390 KiB  
Case Report
Cerebellar Progressive Multifocal Leukoencephalopathy Mimicking Anti-Yo-Antibody-Associated Rapidly Progressive Cerebellar Syndrome
Neurol. Int. 2023, 15(3), 917-925; https://doi.org/10.3390/neurolint15030059 - 26 Jul 2023
Viewed by 859
Abstract
A 58-year-old woman with a history of systemic lupus erythematosus (SLE) who was taking prednisolone and mycophenolate mofetil presented with gait disturbances that progressively worsened over a period of 3 months. Her blood test and cerebrospinal fluid (CSF) examination results did not indicate [...] Read more.
A 58-year-old woman with a history of systemic lupus erythematosus (SLE) who was taking prednisolone and mycophenolate mofetil presented with gait disturbances that progressively worsened over a period of 3 months. Her blood test and cerebrospinal fluid (CSF) examination results did not indicate active SLE. Initial brain magnetic resonance imaging (MRI) revealed a small spotty lesion in the left cerebellar peduncle. The clinical course was consistent with rapidly progressive cerebellar syndrome (RPCS), which sometimes involves neuronal antibodies. The line blot assay detected anti-Yo antibodies, but no malignancy was found. Immunohistological techniques using rat brain sections yielded a negative result for anti-Yo antibodies. The second MRI revealed a focal lesion and surrounding spotty lesion in the left cerebellar peduncle, which was consistent with the punctate pattern observed in progressive multifocal leukoencephalopathy (PML). The CSF JCV-DNA test indicated the presence of cerebellar PML. Immunosuppressants were reduced, and mefloquine and mirtazapine were initiated. After approximately 2 years and 1 month, the CSF JCV-DNA results became negative. Cerebellar PML may exhibit a clinical course that is consistent with RPCS. The punctate pattern should be recognized as an early manifestation of PML. The CSF JCV-DNA copy number may serve as a useful indicator of PML stabilization. Full article
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9 pages, 2169 KiB  
Case Report
Persistent 18F-FDG Brain PET Fronto-Temporal Hypometabolism and Cognitive Symptoms Two Years after SARS-CoV-2 Infection: A Case Report
Neurol. Int. 2023, 15(3), 908-916; https://doi.org/10.3390/neurolint15030058 - 25 Jul 2023
Viewed by 1303
Abstract
At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case [...] Read more.
At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case of persistent cognitive deficits developed after SARS-CoV-2 infection in a 40-year-old woman with a family history of early-onset Alzheimer’s disease (EOAD) since her father was diagnosed with EOAD at the age of 50. We describe the clinical picture and workup, with special emphasis on the alterations of brain glucose metabolism evidenced by 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET), which could be considered a useful marker of the presence and persistence of cognitive deficits. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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12 pages, 1197 KiB  
Article
3D Imaging of Striatal Transplants in a Small Animal Model of Huntington’s Disease
Neurol. Int. 2023, 15(3), 896-907; https://doi.org/10.3390/neurolint15030057 - 24 Jul 2023
Viewed by 812
Abstract
High-resolution imaging in small animal models of neurologic disease is a technical challenge. In a pilot project, we have explored a non-destructive synchrotron imaging technique for the 3D visualization of intracerebral tissue transplants in a well-established small animal model of Huntington’s disease. Four [...] Read more.
High-resolution imaging in small animal models of neurologic disease is a technical challenge. In a pilot project, we have explored a non-destructive synchrotron imaging technique for the 3D visualization of intracerebral tissue transplants in a well-established small animal model of Huntington’s disease. Four adult female Sprague Dawley rats each received injections of 0.12 M quinolinic acid (QA) into two target positions in the left striatum, thus creating unilateral left-sided striatal lesions similar to those frequently seen in patients suffering from Huntington’s disease. One week after lesioning, the animals received transplants prepared from whole ganglionic eminences (wGEs) obtained from 13- to 14-day-old rat embryos. Of the four lesioned animals, three received transplants of GNP-loaded cells and one animal received a transplant of naïve cells, serving as control. Post-mortem synchrotron-based microCT was used to obtain images of the neurotransplants. The images obtained of GNP-loaded tissue transplants at the synchrotron corresponded in size and shape to the histological images of transplants developed from naïve cells. Thus, we conclude that non-destructive synchrotron imaging techniques such as phase-contrast imaging are suitable to obtain high-resolution images of GNP-loaded tissue transplants. Full article
(This article belongs to the Topic Animal Model in Biomedical Research, 2nd Volume)
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15 pages, 660 KiB  
Review
COVID-19 Biomarkers for Critically Ill Patients: A Compendium for the Physician
Neurol. Int. 2023, 15(3), 881-895; https://doi.org/10.3390/neurolint15030056 - 23 Jul 2023
Viewed by 902
Abstract
Background: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of [...] Read more.
Background: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of knowledge regarding known COVID-19 in critical patients. We searched PubMed® using the Boolean operators and identified all results on the PubMed® database of all studies regarding COVID-19 biomarkers. We selected studies regarding endothelium, cytokines, bacterial infection, coagulation, and cardiovascular biomarkers. Methods: We divided the results into four essential paragraphs: “Cytokine storm”, “Endothelium dysfunction and coagulation biomarkers in COVID-19”, “Biomarker of sepsis”, and Cardiovascular lung and new perspectives. Results: The assessments of the severe COVID-19 prognosis should monitor, over time, IL-6, soluble Von Willebrand factor (VWF), P-selectin, sCD40L, thrombomodulin, VCAM-1, endothelin- Troponin, D-dimer, LDH, CRP, and procalcitonin. Metabolomic alterations and ACE2 receptors represent new perspectives. Discussion and Conclusions: Early identification of critically ill patients has been crucial in the first COVID-19 pandemic wave for the sustainability of the healthcare emergency system and clinical management. Only through the early identification of the most severe patients can they be provided with the most appropriate treatments. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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13 pages, 1305 KiB  
Article
Microbiota and Mitochondrial Sex-Dependent Imbalance in Fibromyalgia: A Pilot Descriptive Study
Neurol. Int. 2023, 15(3), 868-880; https://doi.org/10.3390/neurolint15030055 - 12 Jul 2023
Viewed by 1054
Abstract
Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome, mitochondrial imbalance and oxidative stress stand out. Recently, the crosstalk between mitochondria and intestinal microbiota has caught the attention of biomedical [...] Read more.
Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome, mitochondrial imbalance and oxidative stress stand out. Recently, the crosstalk between mitochondria and intestinal microbiota has caught the attention of biomedical researchers, who have found connections between this axis and several inflammatory and pain-related conditions. Hence, this pilot descriptive study focused on characterizing the mitochondrial mass/mitophagy ratio and total antioxidant capacity in PBMCs, as well as some microbiota components in feces, from a Peruvian cohort of 19 females and 7 males with FM. Through Western blotting, electrochemical oxidation, ELISA, and real-time qPCR, we determined VDAC1 and MAP1LC3B protein levels; total antioxidant capacity; secretory immunoglobulin A (sIgA) levels; and Firmicutes/Bacteroidetes, Bacteroides/Prevotella, and Roseburia/Eubacterium ratios; as well as Ruminococcus spp., Pseudomonas spp., and Akkermansia muciniphila levels, respectively. We found statistically significant differences in Ruminococcus spp. and Pseudomonas spp. levels between females and males, as well as a marked polarization in mitochondrial mass in both groups. Taken together, our results point to a mitochondrial imbalance in FM patients, as well as a sex-dependent difference in intestinal microbiota composition. Full article
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11 pages, 20954 KiB  
Opinion
Illustrated Neuropathologic Diagnosis of Alzheimer’s Disease
Neurol. Int. 2023, 15(3), 857-867; https://doi.org/10.3390/neurolint15030054 - 12 Jul 2023
Viewed by 957
Abstract
As of 2022, the prevalence of Alzheimer’s disease (AD) among individuals aged 65 and older is estimated to be 6.2 million in the United States. This figure is predicted to grow to 13.8 million by 2060. An accurate assessment of neuropathologic changes represents [...] Read more.
As of 2022, the prevalence of Alzheimer’s disease (AD) among individuals aged 65 and older is estimated to be 6.2 million in the United States. This figure is predicted to grow to 13.8 million by 2060. An accurate assessment of neuropathologic changes represents a critical step in understanding the underlying mechanisms in AD. The current method for assessing postmortem Alzheimer’s disease neuropathologic change follows version 11 of the National Alzheimer’s Coordinating Center (NACC) coding guidebook. Ambiguity regarding steps in the ABC scoring method can lead to increased time or inaccuracy in staging AD. We present a concise overview of how this postmortem diagnosis is made and relate it to the evolving understanding of antemortem AD biomarkers. Full article
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15 pages, 1990 KiB  
Article
Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease
Neurol. Int. 2023, 15(3), 842-856; https://doi.org/10.3390/neurolint15030053 - 07 Jul 2023
Cited by 1 | Viewed by 1135
Abstract
Background: Individuals with specific TREM2 gene variants that encode for a Triggering Receptor Expressed on Myeloid cells 2 have a higher prevalence of Alzheimer’s disease (AD). By interacting with amyloid and apolipoproteins, the TREM2 receptor regulates the number of myeloid cells, phagocytosis, and [...] Read more.
Background: Individuals with specific TREM2 gene variants that encode for a Triggering Receptor Expressed on Myeloid cells 2 have a higher prevalence of Alzheimer’s disease (AD). By interacting with amyloid and apolipoproteins, the TREM2 receptor regulates the number of myeloid cells, phagocytosis, and the inflammatory response. Higher TREM2 expression has been suggested to protect against AD. However, it is extremely difficult to comprehend TREM2 signaling in the context of AD. Previous results are variable and show distinct effects on diverse pathological changes in AD, differences between soluble and membrane isoform signaling, and inconsistency between animal models and humans. In addition, the relationship between TREM2 and inflammasome activation pathways is not yet entirely understood. Objective: This study aimed to determine the relationship between soluble TREM2 (sTREM2) levels in cerebrospinal fluid (CSF) and plasma samples and other indicators of AD pathology. Methods: Using the Enzyme-Linked Immunosorbent Assay (ELISA), we analyzed 98 samples of AD plasma, 35 samples of plasma from individuals with mild cognitive impairment (MCI), and 11 samples of plasma from healthy controls (HC), as well as 155 samples of AD CSF, 90 samples of MCI CSF, and 50 samples of HC CSF. Results: CSF sTREM2 levels were significantly correlated with neurofibrillary degeneration, cognitive decline, and inflammasome activity in AD patients. In contrast to plasma sTREM2, CSF sTREM2 levels in the AD group were higher than those in the MCI and HC groups. Moreover, concentrations of sTREM2 in CSF were substantially higher in the MCI group than in the HC group, indicating that CSF sTREM2 levels could be used not only to distinguish between HC and AD patients but also as a biomarker to detect earlier changes in the MCI stage. Conclusions: The results indicate CSF sTREM2 levels reliably predict neurofibrillary degeneration, cognitive decline, and inflammasome activation, and also have a high diagnostic potential for distinguishing diseased from healthy individuals. To add sTREM2 to the list of required AD biomarkers, future studies will need to include a larger number of patients and utilize a standardized methodology. Full article
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21 pages, 1052 KiB  
Review
Long COVID, the Brain, Nerves, and Cognitive Function
Neurol. Int. 2023, 15(3), 821-841; https://doi.org/10.3390/neurolint15030052 - 06 Jul 2023
Cited by 3 | Viewed by 3389
Abstract
SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may [...] Read more.
SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored. Full article
(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics)
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17 pages, 701 KiB  
Review
The Effects of Physical Activity in Children and Adolescents with Developmental Coordination Disorder
Neurol. Int. 2023, 15(3), 804-820; https://doi.org/10.3390/neurolint15030051 - 29 Jun 2023
Viewed by 2096
Abstract
The purpose of this literature review was to detect and study the effectiveness of therapeutic intervention programs, such as physical activities and sports, on children and adolescents with Developmental Motor Coordination Disorder (DCD) to improve their motor skills. The sample for this study [...] Read more.
The purpose of this literature review was to detect and study the effectiveness of therapeutic intervention programs, such as physical activities and sports, on children and adolescents with Developmental Motor Coordination Disorder (DCD) to improve their motor skills. The sample for this study consisted of 48 (100%) papers, specifically, 40 (83.5%) articles, 3 (6.2%) doctoral theses, 2 (4.1%) master’s theses and 3 (6.2%) papers from conference proceedings from the year 2014 to 2022. To search the sample, the following terms were used: DCD or dyspraxia, physical activity programs, intervention, physical intervention, physical education, etc. The results for the existence of statistically significant results and internal validity of intervention programs using physical activities and sports in children and adolescents with DCD showed that a large number of intervention programs improved the children’s motor skills as well as their daily functionality. In contrast, other interventions failed to improve dynamic and static balance. The negative result could be due either to the short duration of the interventions or to the improper suboptimal design—organization of the methodology of these programs—such as the heterogeneous intervention samples and the use of inappropriate and reliable assessment tools. Full article
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12 pages, 1774 KiB  
Article
Motor Capabilities in Children with ADHD Are Improved after Brief Visuopostural Training
Neurol. Int. 2023, 15(3), 792-803; https://doi.org/10.3390/neurolint15030050 - 28 Jun 2023
Viewed by 768
Abstract
Children with ADHD show poor motor control. The aim of the present study was to test whether children with ADHD improved their motor performances (oculomotor as well as posture) after a short visuopostural training period. Two groups (G1 trained and G2 non-trained), each [...] Read more.
Children with ADHD show poor motor control. The aim of the present study was to test whether children with ADHD improved their motor performances (oculomotor as well as posture) after a short visuopostural training period. Two groups (G1 trained and G2 non-trained), each comprising 15 children with ADHD matched in IQ (intelligence quotient), sex, and age, participated in the study. Eye movements and postural sway were measured before (T1) and after (T2) 10 min of visuopostural training for the trained group and after 10 min of resting for the non-trained group. Training consisted of a visual search task performed while the child was standing on an unstable platform. At T1, oculomotor and postural abilities were statistically similar for both groups of children with ADHD (trained and non-trained). At T2, significant improvements in both oculomotor and postural capabilities were observed for the trained group but not for the non-trained group. These findings suggest that a short visuopostural training period could help children with ADHD to learn how to focus their visual attention in order to improve motor performance. Visuopostural training could allow a better integration of sensory inputs via central mechanisms, leading to improvement in both oculomotor and postural control. Further studies on a larger number of children with ADHD will be needed to confirm these findings and explore the eventual possible persistence of the training effect. Full article
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14 pages, 2710 KiB  
Article
Contribution of Chronic Sleep Deprivation to Age-Related Neurodegeneration in a Mouse Model of Familial Alzheimer’s Disease (5xFAD)
Neurol. Int. 2023, 15(3), 778-791; https://doi.org/10.3390/neurolint15030049 - 27 Jun 2023
Viewed by 926
Abstract
Sleep–wake cycle disorders most often accompany the elderly and are frequently associated with the development of neurodegenerative processes, primarily Alzheimer’s disease. Sleep disturbances can be diagnosed in patients with AD even before the onset of memory and cognitive impairment, and become more pronounced [...] Read more.
Sleep–wake cycle disorders most often accompany the elderly and are frequently associated with the development of neurodegenerative processes, primarily Alzheimer’s disease. Sleep disturbances can be diagnosed in patients with AD even before the onset of memory and cognitive impairment, and become more pronounced as the disease progresses. Therefore, the expansion of our knowledge of how sleep relates to AD pathogenesis needs to be addressed as soon as possible. Here, we investigated the influence of chronic sleep deprivation on the motor and orienting–exploratory activity of 5xFAD mice, as well as their spatial learning ability and long-term memory retention. The studies carried out revealed that chronic sleep deprivation negatively affects the processes of spatial memory reconsolidation in 5xFAD mice. This leads to the development of stress-related behavioral responses, including aggressive behavior. In addition, the morphological changes in the cerebral cortex, including changes in the nuclear–cytoplasmic ratio and degradation of neuronal processes are observed. Moreover, we found an increase in the level of total DNA methylation in the blood of the sleep-deprived mice, which may be one of the mechanisms of the two-way relationship between sleep and neurodegeneration. Full article
(This article belongs to the Topic Translational Advances in Neurodegenerative Dementias)
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14 pages, 526 KiB  
Review
Long Sleep Duration and Stroke—Highly Linked, Poorly Understood
Neurol. Int. 2023, 15(3), 764-777; https://doi.org/10.3390/neurolint15030048 - 25 Jun 2023
Cited by 2 | Viewed by 1029
Abstract
Stroke is one of the leading causes of disability and mortality. Both short and long sleep durations are associated with adverse health outcomes. Cross-sectional studies have shown an increased prevalence of stroke in long sleepers. Long sleep duration increases stroke incidence and mortality [...] Read more.
Stroke is one of the leading causes of disability and mortality. Both short and long sleep durations are associated with adverse health outcomes. Cross-sectional studies have shown an increased prevalence of stroke in long sleepers. Long sleep duration increases stroke incidence and mortality in prospective epidemiological studies. Accumulating evidence suggests that the magnitude of the association between sleep and stroke appears to be stronger for longer sleep than shorter sleep, yielding a J-shaped curve. Potential links between long sleep duration and stroke include increased incidence of diabetes and atrial fibrillation, elevated levels of inflammation, arterial stiffness, and blood pressure variability. Long sleep duration is a strong marker and a plausible risk factor for stroke and should be considered in future scoring for risk stratification and stroke prevention. Full article
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