Nervous System Impairment Research Articles

Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms.

Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.

Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.

Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

Cardiac remodeling, amyloidosis, neurotrophic signaling and innervation impairment in the Tg2576 model of Alzheimer’s disease

AbstractBackgroundIn Alzheimer’s disease (AD), the characteristic cerebral amyloid β (Aβ) accumulation and tau pathology, are accompanied by a gradual loss of the two main neuromodulators, NGF and BDNF. This AD‐mediated derangement of the brain’s neuro‐signaling pathways may extend to the periphery and, along with potential peripheral amyloid deposition, induce peripheral nervous system impairment, thus affecting other organs, including the heart. However, whether and how AD pathology affects cardiac physiology, neurotrophins, innervation, and heart amyloidosis is still undefined.MethodHere, we describe for the first‐time that cardiac remodeling and neuro‐signaling dysregulation are present in the hearts of Tg2576 mice, a widely used model of AD and cerebral amyloidosis.ResultsEchocardiographic analysis showed significant deterioration of left ventricle function, as demonstrated by a decline of both ejection fraction and fraction shortening in 12‐month‐old Tg2576 mice compared to age‐matched WT littermates. The transgenic mice hearts presented an increase in interstitial fibrosis, with an accumulation of amyloid aggregates, including Aβ, associated with severe cardiac nervous system dysfunction. Tg2576 mice exhibited a depletion in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase‐ TH) and regenerating nerve terminals (labeled with GAP‐43) compared to the WT mice. This myocardial denervation was accompanied by a decline in NGF and BDNF protein expression as well as GAP‐43 expression in both the brain and heart of Tg2576 mice. Likewise, both human neuroblastoma cells (SH‐SY5Y) and human cardiomyocytes (AC16) challenged with human Aβ‐40 or Aβ‐42 oligomers showed significant downregulation of both BDNF and GAP‐43 activity.ConclusionOverall, this study highlights the deleterious impact of cerebral amyloidosis on the cardiac nervous system and heart physiology, providing potential therapeutic targets, such as neurotrophic factors, to prevent or limit the AD‐mediated degenerative mechanisms on the cardiovascular system.

Molecular underpinnings underlying behaviors changes in the brain of juvenile common carp (Cyrinus carpio) in response to warming

IntroductionGlobal warming is increasing interest in how aquatic animals can adjust their physiological performance and cope with temperature changes. Therefore, understanding the behavioral changes and molecular underpinnings in fish under warming is crucial for both the individual and groups survival. This could provide experimental evidence and resource for evaluating the impact of global warming. ObjectiveThree genetic families of common carp (Cyprinus carpio) were generated. These juveniles were constructed short-term (4 days) and long-term (30 days) warming groups to investigate the effects of warming on behavioral responses and to elucidate the potential underlying mechanisms of warming-driven behavior. MethodsBehavioral tests were used to explore the effects of short- and long-term exposure to warming on the swimming behavior of C. carpio. Brain transcriptome combined with measurement of nervous system activity was used to further investigated the comprehensive neuromolecular mechanisms under warming. ResultsLong-term warming groups had a more significant impact on the decline of swimming behavior in juvenile C. carpio. Furthermore, brain comparative transcriptomic analysis combined with measurement of nervous system activity revealed that genes involved in cytoskeletal organization, mitochondrial regulation, and energy metabolism are major regulators of behavior in the juvenile under warming. Importantly, especially in the long-term warming groups, enrichment analysis of associated gene expression suggested functional alterations of synaptic transmission and signal transduction leading to swimming function impairment in the central nervous system, as revealed by behavioral tests. ConclusionsOur study provides evidence of the neurogenomic mechanism underlying the decreased swimming activity in juvenile C. carpio under warming. These findings have important implications for understanding the impacts of climate change on aquatic ecosystems and the organisms that inhabit them.

Biological Pathways Associated with Vitamins in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by early-appearing social communication deficits, with genetic and environmental factors potentially playing a role in its etiology, which remains largely unknown. During pregnancy, certain deficiencies in critical nutrients are mainly associated with central nervous system impairment. The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation. In addition, supplementation with folic acid (FA) is recommended by the World Health Organization (WHO) in the first three gestational months to prevent neural tube defects. Vitamin B12 is related to folate regeneration, converting it into an active form. Deficiencies in this vitamin have a negative impact on cognitive function and brain development since it is involved in myelin synthesis. Vitamin D is intimately associated with Ca2+ levels, acting in bone development and calcium-dependent signaling. This vitamin is associated with ASD at several levels since it has a relation with ASD genes and oxidative stress environment. This review carries the recent literature about the role of folate, vitamin B12, and vitamin D in ASD. In addition, we discuss the possible impact of nutrient deficiency or hypersupplementation during fetal development. On the other hand, we explore the biases of vitamin supplementation studies such as the loss of participants in retrospective studies, as well as multiple variants that are not considered in the conclusion, like dietary intake or auto-medication during pregnancy. In this regard, we aim to contribute to the discussion about the role of vitamins in ASD currency, but also in pregnancy and fetal development as well. Furthermore, stress during pregnancy can be an ASD predisposition, with cortisol as a regulator. In this view, we propose that cortisol is the bridge of susceptibility between vitamin disorders and ASD prevalence.

Two non-familial cases of Galloway-Mowat syndrome carrying the homozygous mutations of WDR73 and TP53RK

Galloway–Mowat syndrome (GAMOS) is a rare hereditary disease manifested as a combination of nephrotic syndrome and central nervous system impairment. To date, many GAMOS cases attributed to various gene mutations have been reported such as WHAMM, NUP107, WDR73, OSGEP, and TP53RK. We detected two novel homozygous mutations of WDR73 ‘’NM_032856:c.G287A:p.R96K‘’ and TP53RK ‘’NM_033550:c.A193O:p.K65Q‘’ in two female kids of the consanguineous parents from different families using whole exome sequencing. Both patients almost manifested similar neurodegenerative phenotypes, including developmental delay, microcephaly, hypotonia, and brain atrophy on magnetic resonance imaging during infancy. WDR73-positive GAMOS case manifested a late-onset minimal nephrotic syndrome at the age 4 years while TP53RK-positive case presented nephrotic syndrome at the age 1 which progressed to steroid-resistant nephrotic syndrome due to lack of remission after 4-6 weeks of initial treatment with prednisone. Despite the brain abnormalities and the onset time difference of renal abnormalities, both patients are still alive. Given the heterogeneity of the renal phenotype among GAMOS types, accurate recognition of expanding spectrum of phenotype findings and regular renal function screening are necessary for an early diagnosis and timely treatment.

Antibody Deficiency in Patients with Biallelic KARS1 Mutations.

Biallelic KARS1 mutations cause KARS-related diseases, a rare syndromic condition encompassing central and peripheral nervous system impairment, heart and liver disease, and deafness. KARS1 encodes the t-RNA synthase of lysine, an aminoacyl-tRNA synthetase, involved in different physiological mechanisms (such as angiogenesis, post-translational modifications, translation initiation, autophagy and mitochondrial function). Although patients with immune-hematological abnormalities have been individually described, results have not been collectively discussed and functional studies investigating how KARS1 mutations affect B cells have not been performed.Here, we describe one patient with severe developmental delay, sensoneurinal deafness, acute disseminated encephalomyelitis, hypogammaglobulinemia and recurrent infections. Pathogenic biallelic KARS1 variants (Phe291Val/ Pro499Leu) were associated with impaired B cell metabolism (decreased mitochondrial numbers and activity). All published cases of KARS-related diseases were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Seventeen patients with KARS-related diseases were identified. Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) were frequently reported. Immunoglobulin replacement therapy was given in five patients. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment.

Magnetic resonance spectroscopy findings of brain olfactory areas in patients with COVID‐19‐related anosmia: A preliminary comparative study

AbstractObjectives2019 novel coronavirus disease (COVID‐19) infection is commonly associated with olfactory dysfunctions, but the basic pathogenesis of these complications remains controversial. This study seeks to evaluate the value of magnetic resonance spectroscopy (MRS) in determining the molecular neurometabolite alterations within the main brain olfactory areas in patients with COVID‐19‐related anosmia.MethodsIn a cross‐sectional study, seven patients with persistent COVID‐19‐related anosmia (mean age: 29.57 years) and seven healthy volunteers (mean age: 27.28 years) underwent MRS in which N‐acetyl‐aspartate (NAA), choline (Cho), creatine (Cr), and their ratios were measured in the anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex (OFC), insular cortex, and ventromedial prefrontal cortex. Data were analyzed using TARQUIN software (version 4.3.10), and the results were compared with an independent sample t‐test and nonparametric Mann–Whitney test based on the normality of the MRS data distribution.ResultsThe mean duration of anosmia before imaging was 8.5 months in COVID‐19‐related anosmia group. MRS analysis elucidated a significant association between MRS findings within OFC and COVID‐19‐related anosmia (Pdisease < 0.01), and NAA was among the most important neurometabolites (Pinteraction = 0.006). Reduced levels of NAA (P < 0.001), Cr (P < 0.001) and NAA/Cho ratio (P = 0.007) within OFC characterize COVID‐19‐related anosmia.ConclusionsThis study emphasizes that MRS can be illuminating in COVID‐19‐related anosmia and indicates a possible association between central nervous system impairment and persistent COVID‐19‐related anosmia.

Aluminum exposure induces central nervous system impairment via activating NLRP3-medicated pyroptosis pathway

PurposeAluminum is an environmental toxicant whose long-term exposure is closely associated with nervous system impairment. This study mainly investigated neurological impairment induced by subchronic aluminum exposure via activating NLRP3-medicated pyroptosis pathway. MethodsIn vivo, Kunming mice were exposed to AlCl3 (30.3 mg/kg, 101 mg/kg and 303 mg/kg) via drinking water for 3 months, and administered with Rsv (100 mg/kg) by gavage for 1 month. Cognitive impairment was assessed by Morris water maze test, and pathological injury was detected via H&E staining. BBB integrity, pyroptosis and neuroinflammation were evaluated through western blotting and immunofluorescence methods. In vitro, BV2 microglia was treated with AlCl3 (0.5 mM, 1 mM and 2 mM) to sensitize pyroptosis pathway. The protein interaction was verified by co-immunoprecipitation, and neuronal damage was estimated via a conditioned medium co-culture system with BV2 and TH22 cells. ResultsOur results showed that AlCl3 induced mice memory disorder, BBB destruction, and pathological injury. Besides, aluminum caused glial activation, sensitized DDX3X-NLRP3 pyroptosis pathway, released cytokines IL-1β and IL-18, initiating neuroinflammation. BV2 microglia treated with AlCl3 emerged hyperactivation and pyroptotic death, and Ddx3x knockdown inhibited pyroptosis signaling pathway. DDX3X acted as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome and G3BP1 stress granules. Furthermore, aluminum-activated microglia had an adverse effect on co-cultured neurons and destroyed nervous system homeostasis. ConclusionAluminum exposure could induce pyroptosis and neurotoxicity. DDX3X determined live or die via selectively regulating pro-survival stress granules or pro-death NLRP3 inflammasome. Excessive activation of microglia might damage neurons and aggravate nerve injury.

Relationship between Cognitive Impairment and Depressive Symptoms with Somatosensory Functions in Diabetic and Non-Diabetic Older Adults and Its Impact on Quality of Life.

Aging is an inevitable process that impacts the peripheral and central nervous systems and is considered one of the strongest risk factors for neurodegenerative diseases. In addition, when it also presents with diabetes mellitus, the risk of neurological damage may be further increased. This current study aimed to explore the relationships between peripheral sensory system decline and cognitive functions, the symptoms of depression, and quality of life (QoL) as metrics of central nervous system impairment in institutionalized older adults. A total of 95 individuals participated in this case-control study, which included diabetics and non-diabetics. The superficial sensory pathway was assessed in terms of thermal sensation, nociception, and non-discriminative touch, and the deep sensory pathway was evaluated by assessing vibration and light touch-pressure sensations. To assess function at the intellectual level, the Mini-Mental State Examination (MMSE) and Trail Making Test (TMT) cognitive functional tests were used, while the symptoms of depression and QoL were explored by employing the Yesavage Geriatric Depression Scale and EuroQol 5D questionnaire (EQ-5D), respectively. In the overall population analyses, altered thermal sensation was significantly associated with cognitive impairment (CI; p < 0.05). In turn, bivariate analyses and a binary logistic regression showed that the symptoms of depression and QoL were significantly related to altered vibratory sensation when assessed using a medical tuning fork (p < 0.05). In the group of diabetic patients, those with CI also had significantly lower thermal sensation (p < 0.05) and non-discriminative touch sensation, although this was only a trend (p = 0.055). Diabetics with depression had a significantly worse non-discriminative touch (p < 0.05) and vibratory sensation when tested with a tuning fork (p < 0.05). In addition, poorer QoL was associated with reduced sensitivity to heat (p < 0.05), light touch pressure (p < 0.05), and vibrations when assessed either with a tuning fork (p < 0.05) or a biothesiometer (p < 0.05). In contrast, no relationships were found between sensory functions and cognitive assessments in non-diabetic patients. These findings indicate that superficial sensitivity damage was related to CI, while deep sensation alterations were related to depression and poor QoL, with diabetes apparently further strengthening these relationships.

Alcohol—dose question and the weakest link in a chemical interplay

The deleterious consequences of alcohol consumption are extensively documented across various dimensions of human health, encompassing somatic disorders such as nervous system impairments, digestive system abnormalities, and circulatory dysfunctions, in addition to socio-psychological aspects. Within the domain of cardiology, a substantial portion of the ongoing scientific discourse centers on elucidating the toxic dose of alcohol. Presented herewith are the findings from a comprehensive review of the latest publications pertinent to this crucial issue.

Abstract P2013: Cardiac Remodeling, Amyloidosis, Neurotrophic Signaling, And Innervation Impairment In The Tg2576 Model Of Alzheimer's Disease

Background: In Alzheimer's disease (AD), the characteristic cerebral amyloid β (Aβ) deposition and tau pathology are accompanied by a progressive loss of the two main neuromodulators, NGF and BDNF. This AD-mediated derangement of the brain's neuro-signaling pathway may extend to the periphery and, along with potential peripheral amyloid deposition, induce peripheral nervous system impairment, thus affecting other organs, including the heart. However, whether and how AD pathology affects cardiac physiology, neurotrophins, innervation, and heart amyloidosis is still unclear. Method: Here, we describe for the first time that cardiac remodeling and neuro-signaling dysregulation are present in the hearts of Tg2576 mice, a widely used model of AD and cerebral amyloidosis. Results: Echocardiographic analysis showed significant deterioration of left ventricle function, as demonstrated by a decline of both ejection fraction and fraction shortening in 12-month-old Tg2576 mice compared to age-matched WT littermates. The transgenic mice hearts displayed an increase in interstitial fibrosis, with an accumulation of amyloid aggregates, including Aβ, associated with severe cardiac nervous system dysfunction. Tg2576 mice exhibited a depletion in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase- TH) and regenerating nerve terminals (labeled with GAP-43), compared to the WT mice. This myocardial denervation was accompanied by a decline in NGF and BDNF protein expression as well as GAP-43 expression in both the brain and heart of Tg2576 mice. Likewise, human neuroblastoma cells (SH-SY5Y) and human cardiomyocytes (AC16) challenged with human Aβ-40 or, Aβ-42 oligomers showed significant downregulation of both BDNF and GAP-43 activity. Conclusion: Overall, this study highlights the harmful impact of cerebral amyloidosis on the cardiac nervous system and heart physiology, providing potential therapeutic targets, such as neurotrophic factors, to prevent or limit AD-mediated degenerative mechanisms in the cardiovascular system.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

Severe anaphylactic reactions to home doses may occur during food allergy oral immunotherapy (OIT). To study the rate and risk factors for such reactions. We studied all patients aged greater than 3.5 years who completed OIT in a single center between April 2010 and January 2020. All home epinephrine-treated reactions (HETRs) were identified. High-grade HETRs (HG-HETRs) were defined as HETRs involving respiratory (SpO2 of 94% or less), cardiovascular (low blood pressure), or central nervous system impairment (loss of consciousness). We investigated the rate and risk factors for HG-HETRs. A total of 1,637 OIT treatments were studied: milk (880), peanut (346), tree nuts (221), sesame (115), and egg (75). Of 390 identified HETRs, 30 HG-HETRs occurred during 27 treatments (1.65% of all treatments). Nearly all (26 of 30) were during milk OIT in patients with house dust mite (HDM) sensitization and asthma (26 of 30 each). Of the 30 patients with HG-HETRs, 21 recovered with one or two epinephrine treatments, but nine (0.55% of all treatments) did not respond to a second dose of epinephrine and were deemed to have refractory anaphylaxis. Three patients required intensive care unit admission and three received epinephrine drip, but none required ventilatory support. Risk factors for HG-HETRs included milk OIT (P= .031), asthma (P= .02) and HDM sensitization (P= .02). No specific triggers for HG-HETR were identified. Of patients with HG-HETRs, 25.9% were fully desensitized, including the four non-milk treated patients; 22.2% were partially desensitized; and 51.9% failed. High-grade HETRs are uncommon, particularly refractory anaphylactic reactions to home OIT doses. Although milk OIT, asthma, and HDM sensitization are the main risk factors for such reactions, identification of patients who are at risk is challenging.

The GABA system, a new target for medications against cognitive impairment-Associated with neuroactive steroids.

The prevalence of cognitive dysfunction, dementia, and neurodegenerative disorders such as Alzheimer's disease (AD) is increasing in parallel with an aging population. Distinct types of chronic stress are thought to be instrumental in the development of cognitive impairment in central nervous system (CNS) disorders where cognitive impairment is a major unmet medical need. Increased GABAergic tone is a mediator of stress effects but is also a result of other factors in CNS disorders. Positive GABA-A receptor modulating stress and sex steroids (steroid-PAMs) such as allopregnanolone (ALLO) and medroxyprogesterone acetate can provoke impaired cognition. As such, ALLO impairs memory and learning in both animals and humans. In transgenic AD animal studies, continuous exposure to ALLO at physiological levels impairs cognition and increases degenerative AD pathology, whereas intermittent ALLO injections enhance cognition, indicating pleiotropic functions of ALLO. We have shown that GABA-A receptor modulating steroid antagonists (GAMSAs) can block the acute negative cognitive impairment of ALLO on memory in animal studies and in patients with cognitive impairment due to hepatic encephalopathy. Here we describe disorders affected by steroid-PAMs and opportunities to treat these adverse effects of steroid-PAMs with novel GAMSAs.

Ageing reduces persistent inward current contribution to motor neurone firing: Potential mechanisms and the role of exercise.

Nervous system deterioration is a primary driver of age-related motor impairment. The motor neurones, which act as the interface between the central nervous system and the muscles, play a crucial role in amplifying excitatory synaptic input to produce the desired motor neuronal firing output. For this, they utilise their ability to generate persistent (long-lasting) depolarising currents that increase cell excitability, and both amplify and prolong the output activity of motor neurones for a given synaptic input. Modulation of these persistent inward currents (PICs) contributes to the motor neurones' capacities to attain the required firing frequencies and rapidly modulate them to competently complete most tasks. Thus, PICs are crucial for adequate movement generation. Impairments in intrinsic motor neurone properties can impact motor unit firing capacity, with convincing evidence indicating that the PIC contribution to motor neurone firing is reduced in older adults. Indeed, this could be an important mechanism underpinning the age-related reductions in strength and physical function. Furthermore, resistance training has emerged as a promising intervention to counteract age-associated PIC impairments, with changes in PICs being correlated with improvements in muscular strength and physical function after training. In this review, we present the current knowledge of the PIC magnitude decline during ageing and discuss whether reduced serotonergic and noradrenergic input onto the motor neurones, voltage-gated calcium channel dysfunction or inhibitory input impairments are candidates that: (i) explain age-related reductions in the PIC contribution to motor neurone firing and (ii) underpin the enhanced PIC contribution to motor neurone firing following resistance training in older adults.

Umbilical mesenchymal stem cell-derived exosomes promote spinal cord functional recovery through the miR-146b/TLR4 -mediated NF-κB p65 signaling pathway in rats

Spinal cord injury (SCI) is an incurable central nervous system impairment that lack of efficient treatment. Exosomes derived from mesenchymal stem cells (MSCs) are widely applied in disease treatment. This work aimed to determine the promising therapeutic effects of MSC-derived exosomal miRNA146b on SCI. A rat spinal cord injury (SCI) model and lipopolysaccharide (LPS)-induced PC12 cell model were established. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs). The identification of exosomes was performed by using transmission electronic microscope (TEM) and nanoparticle tracking analysis (NTA). Hematoxylin and eosin (HE) staining and TUNEL assay were performed to assess tissue damage and apoptosis, respectively. ELISA was performed to detect levels of inflammatory cytokines. Cell viability was checked by cell counting kit 8 (CCK-8). Gene expression and protein levels were detected by qPCR and western blotting assay. The interaction between miR-146 b and Toll-like receptor 4 (TLR4) was assessed by luciferase reporter gene assay. The hUCMSC-derived exosomes could notably alleviate the spinal cord injury and cell apoptosis. The exosomal miR-146 b treatment suppressed the release of IL-1 β, IL-6, and TNFα. The miR-146 b suppressed the expression of TLR4, directly interact with the 3′-untranslated region (3′UTR) of TLR4, and inactivated the nuclear factor κB (NF-κB) signaling. The hUCMSCs-derived exosomal miR-146 b protects neurons from spinal cord injury through targeting the TLR4 and inactivating the NF-κB signaling. Our findings supported the application of hUCMSCs-derived exosomal miR-146 b for the protection of SCI.

The Protective Effects of Melatonin against Brain Disorders Induced by the Western Diet in Male Rats

Globally, the effects of consuming a diet rich in fat have gained great concerted attention. The current study was conducted to evaluate the protective effects of melatonin on neurological disorders induced by the western diet in rats. A total of 30 adult male white local Iraqi rats were randomly assigned to three equal groups, including control (CC), high-fat diet (HFD), and melatonin group (HFD+M, a high-fat diet along with intraperitoneal injections of 10 mg/kg body weight melatonin) for 8 weeks. The rats were analyzed in terms of brain tissue concentration of dopamine, tumor necrosis factor (TNF), and nervous system impairment using Barns maze task and elevated plus maze. The findings revealed a significant decline in the dopamine concentration of the HFD group after 8 weeks of treatment, compared to CC and HFD+M groups. Moreover, there was a significant increase in brain TNF-α concentration in the group fed HFD, compared with CC and HFD+M. Finally, the melatonin treatment significantly reduced spatial memory impairments and anxiety induced by HFD in rats. After 8 weeks, the histological examination revealed that brain section rats on an HFD indicated significant congestion in the blood vessels with marked cerebral edema, where there was a dilation of Virchow-Robin space, severe congestion, and infiltration of inflammatory cells in the meninges. The HFD+M groups showed normal meninges without any inflammatory exudate except for a few congestions in the blood vessels and no or mild vacuolations in the cerebral tissue, gliosis, and astrocytosis. In contrast, male rats fed an HFD showed vacuolation and aerophagia in brain tissue and a marked aggregation of the proliferation of astrocytes and a proliferation of microglial cells in the cerebral. In conclusion, HFD impairs brain neurotransmitters, induces pro-inflammatory changes, and affects learning ability and memory by changing the structure of neural tissue. Melatonin can ameliorate HFD-caused effects.

Neurological Considerations for "Nerve-Sparing" Cosmetic Genital Surgeries Performed on Children with XX Chromosomes Diagnosed with 21-Hydroxylase Congenital Adrenal Hyperplasia and Clitoromegaly.

Congenital adrenal hyperplasia (CAH) is most often caused by adrenal deficiency of 21-hydroxylase (21-OH). The resulting increase in androgens can cause clitoromegaly in fetuses with XX chromosomes. 21-OH CAH is the most common reason for cosmetic clitoroplasty in childhood. "Nerve-sparing" (NS) clitoral reduction surgeries are described as offering optimal cosmesis, while sparing sensation and nerve function. The methods used to demonstrate NS surgery efficacy, however, such as electromyography and optical coherence tomography, do not evaluate the small-fiber axons that comprise the majority of axons in the clitoris and that transduce sexual pleasure. Although some data show sparing of a portion of the main dorsal nerve trunk of the clitoris, the overall neurobiological consequences of elective clitoral reductions have received little attention. NS surgeries remove dorsal nerve branches that transduce sexual sensation, as well as the corpora cavernosa and cavernous nerve, which provide clitoral autonomic function. While most outcome studies focus on surgeons' perceptions of cosmetic results, studies that assess small-fiber function indicate significant nervous system and sexual impairment. Studies assessing children's clitoral function after surgery with vibrational testing have been ethically condemned. Decades of advocacy against medically unnecessary childhood genital surgeries have highlighted the subsequent physical and psychological harm. Recent studies with CAH patients indicate gender diversity and a lower prevalence of female gender identification than is often cited to justify feminizing surgery. The most effective and ethical NS technique for CAH may be acceptance of gender, sexual, and genital diversity as the infant develops into childhood, adolescence, and adulthood.

Evaluating 3D human face reconstruction from a frontal 2D image, focusing on facial regions associated with foetal alcohol syndrome

Foetal alcohol syndrome (FAS) is a preventable condition caused by maternal alcohol consumption during pregnancy. The FAS facial phenotype is an important factor for diagnosis, alongside central nervous system impairments and growth abnormalities. Current methods for analysing the FAS facial phenotype rely on 3D facial image data, obtained from costly and complex surface scanning devices. An alternative is to use 2D images, which are easy to acquire with a digital camera or smart phone. However, 2D images lack the geometric accuracy required for accurate facial shape analysis. Our research offers a solution through the reconstruction of 3D human faces from single or multiple 2D images. We have developed a framework for evaluating 3D human face reconstruction from a single-input 2D image using a 3D face model for potential use in FAS assessment. We first built a generative morphable model of the face from a database of registered 3D face scans with diverse skin tones. Then we applied this model to reconstruct 3D face surfaces from single frontal images using a model-driven sampling algorithm. The accuracy of the predicted 3D face shapes was evaluated in terms of surface reconstruction error and the accuracy of FAS-relevant landmark locations and distances. Results show an average root mean square error of 2.62 mm. Our framework has the potential to estimate 3D landmark positions for parts of the face associated with the FAS facial phenotype. Future work aims to improve on the accuracy and adapt the approach for use in clinical settings. Significance: Our study presents a framework for constructing and evaluating a 3D face model from 2D face scans and evaluating the accuracy of 3D face shape predictions from single images. The results indicate low generalisation error and comparability to other studies. The reconstructions also provide insight into specific regions of the face relevant to FAS diagnosis. The proposed approach presents a potential cost-effective and easily accessible imaging tool for FAS screening, yet its clinical application needs further research.

Two Cases of Acute Focal Bacterial Nephritis With Central Nervous System Manifestations in Children and Literature Review.

Acute focal bacterial nephritis (AFBN) is a kidney disease characterized by a localized bacterial infection that manifests as an inflammatory mass. Most children with AFBN have nonspecific symptoms including fever, vomiting, and abdominal discomfort, and some develop neurological symptoms such as meningeal irritation, unconsciousness, and seizures as their condition worsens. This was 2 cases of AFBN with central nervous system manifestations in children, and we analyzed its possible mechanisms of the clinical and radiographic features. We experience 2 very unusual cases of AFBN which were linked to central nervous system abnormalities. A 6-year-old boy with AFBN and clinically moderate ncephalitis/encephalopathy with a reversible splenial lesion (MERS) presented with neurological symptoms, including unconsciousness and convulsions. The second case involved an 8-year-old child with AFBN-associated acute encephalopathy who exhibited neurological symptoms, including unconsciousness. According to previous research, AFBN is linked to central nervous system impairment. As a result, when a clinician meets a patient with an inexplicable fever caused by a neurological condition, he should pay attention to this diagnosis of AFBN and follow it in the abdominal graph.