Progressive Neurological Disorder Research Articles

NMR-based metabolomics identification of potential serum biomarkers of disease progression in patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic and progressive neurological disorder, characterized by neuroinflammation and demyelination within the central nervous system (CNS). The etiology and the pathogenesis of MS are still unknown. Till now, no satisfactory treatments, diagnostic and prognostic biomarkers are available for MS. Therefore, we aimed to investigate metabolic alterations in patients with MS compared to controls and across MS subtypes. Metabolic profiles of serum samples from patients with MS (n = 90) and healthy control (n = 30) were determined by Nuclear Magnetic Resonance (1H-NMR) Spectroscopy using cryogenic probe. This approach was also utilized to identify significant differences between the metabolite profiles of the MS groups (primary progressive, secondary progressive, and relapsing–remitting) and the healthy controls. Concentrations of nine serum metabolites (adenosine triphosphate (ATP), tryptophan, formate, succinate, glutathione, inosine, histidine, pantothenate, and nicotinamide adenine dinucleotide (NAD)) were significantly higher in patients with MS compared to control. SPMS serum exhibited increased pantothenate and tryptophan than in PPMS. In addition, lysine, myo-inositol, and glutamate exhibited the highest discriminatory power (0.93, 95% CI 0.869–0.981; 0.92, 95% CI 0.859–0.969; 0.91, 95% CI 0.843–0.968 respectively) between healthy control and MS. Using NMR- based metabolomics, we identified a set of metabolites capable of classifying MS patients and controls. These findings confirmed untargeted metabolomics as a useful approach for the discovery of possible novel biomarkers that could aid in the diagnosis of the disease.

Relationship of Curcumin with Aging and Alzheimer and Parkinson Disease, the Most Prevalent Age-Related Neurodegenerative Diseases: A Narrative Review.

The elderly population is increasing worldwide every day. Age is a significant factor in the progression of neurological diseases, which can also cause cognitive decline and memory disorders. Inflammation and oxidative stress are primary drivers of senescence and disorders, particularly those associated with aging and neurodegenerative diseases. Bioactive phytochemicals are considered a promising therapeutic strategy in combating aging and age-related pathological conditions. One of the phytochemicals with diverse biological properties encompassing antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, antifungal, antidepressant, anti-allergic, and anti-aging properties is curcumin. Curcumin, a polyphenolic structure with a distinct orange hue and unique chemical properties, is derived from the roots of Curcuma longa, a member of the Zingiberaceae family, commonly known as turmeric. It has been noted that the incidence of neurodegenerative diseases is low in societies that consume curcumin widely. Therefore, this review investigates the effect of curcumin on aging and Alzheimer and Parkinson disease, which are the most prevalent age-related neurodegenerative diseases.

Using Synbiotics as a Therapy to Protect Mental Health in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurological disorder that represents a major cause of dementia worldwide. Its pathogenesis involves multiple pathways, including the amyloid cascade, tau protein, oxidative stress, and metal ion dysregulation. Recent studies have suggested a critical link between changes in gut microbial diversity and the disruption of the gut-brain axis in AD. Previous studies primarily explored the potential benefits of probiotics and prebiotics in managing AD. However, studies have yet to fully describe a novel promising approach involving the use of synbiotics, which include a combination of active probiotics and new-generation prebiotics. Synbiotics show potential for mitigating the onset and progression of AD, thereby offering a holistic approach to address the multifaceted nature of AD. This review article primarily aims to gain further insights into the mechanisms of AD, specifically the intricate interaction between gut bacteria and the brain via the gut-brain axis. By understanding this relationship, we can identify potential targets for intervention and therapeutic strategies to combat AD effectively. This review also discusses substantial evidence supporting the role of synbiotics as a promising AD treatment that surpasses traditional probiotic or prebiotic interventions. We find that synbiotics may be used not only to address cognitive decline but also to reduce AD-related psychological burden, thus enhancing the overall quality of life of patients with AD.

A Computational Model of Deep Brain Stimulation for Parkinson's Disease Tremor and Bradykinesia.

Parkinson's disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents.

Impact of Ocrelizumab on Disease Progression, Memory Improvement, and Quality of Life in Patients with Relapsing-Remitting Multiple Sclerosis: A Longitudinal MRI and Clinical Criteria Analysis.

Multiple sclerosis (MS) is a chronic, progressive neurological disorder that significantly impacts quality of life and functionality. Ocrelizumab, a monoclonal antibody targeting CD20-positive B cells, has emerged as a treatment for relapsing-remitting MS (RRMS). This study aimed to assess the impact of ocrelizumab on disease progression and quality of life over a longitudinal course, utilizing clinical criteria and magnetic resonance imaging (MRI) analyses. Conducted at the Neurology Department of Pius Brinzeu Clinical Emergency Hospital in Western Romania from 2020 to 2023, this observational study enrolled 93 patients with RRMS who commenced ocrelizumab therapy. The study employed the Expanded Disability Status Scale (EDSS) and MRI to evaluate disease progression, while quality of life was assessed using the World Health Organisation Quality of Life (WHOQOL) questionnaire, Beck Depression Index (BDI), and MOCA scales. Significant improvements were observed post-treatment. EDSS scores decreased from 4.61 to 4.08 (p = 0.038), indicating reduced disability. MRI analyses showed a substantial decrease in expansive lesions (from 67.74% to 26.88%, p < 0.001) and an increase in stationary lesions (from 32.26% to 73.12%, p < 0.001). Quality of life improvements were notable in the physical (from 58.42 to 64.84, p = 0.005) and environmental domains (from 63.21 to 68.44, p = 0.033). Cognitive functions, assessed via Montreal Cognitive Assessment (MOCA), showed a significant total score increase from 20.38 to 22.30 (p < 0.001). Subgroup analysis revealed more pronounced effects in females and younger patients, with a significant reduction in depressive symptoms measured by BDI scores (from 14.35 to 11.62, p = 0.003). Ocrelizumab significantly reduced disease activity and disability in RRMS patients, as demonstrated by improvements in EDSS scores and MRI findings. Quality of life and cognitive functions also showed considerable enhancements. These findings support ocrelizumab's efficacy in not only managing MS symptoms but also improving overall patient well-being.

Multimodal deep learning for dementia classification using text and audio

Dementia is a progressive neurological disorder that affects the daily lives of older adults, impacting their verbal communication and cognitive function. Early diagnosis is important to enhance the lifespan and quality of life for affected individuals. Despite its importance, diagnosing dementia is a complex process. Automated machine learning solutions involving multiple types of data have the potential to improve the process of automated dementia screening. In this study, we build deep learning models to classify dementia cases from controls using the Pitt Cookie Theft dataset from DementiaBank, a database of short participant responses to the structured task of describing a picture of a cookie theft. We fine-tune Wav2vec and Word2vec baseline models to make binary predictions of dementia from audio recordings and text transcripts, respectively. We conduct experiments with four versions of the dataset: (1) the original data, (2) the data with short sentences removed, (3) text-based augmentation of the original data, and (4) text-based augmentation of the data with short sentences removed. Our results indicate that synonym-based text data augmentation generally enhances the performance of models that incorporate the text modality. Without data augmentation, models using the text modality achieve around 60% accuracy and 70% AUROC scores, and with data augmentation, the models achieve around 80% accuracy and 90% AUROC scores. We do not observe significant improvements in performance with the addition of audio or timestamp information into the model. We include a qualitative error analysis of the sentences that are misclassified under each study condition. This study provides preliminary insights into the effects of both text-based data augmentation and multimodal deep learning for automated dementia classification.

Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review.

Tau protein is a microtubule-associated protein that is widely distributed in the central nervous system and maintains and regulates neuronal morphology and function. Tau protein aggregates abnormally and forms neurofibrillary tangles in neurodegenerative diseases, disrupting the structure and function of neurons and leading to neuronal death, which triggers the initiation and progression of neurological disorders. The aggregation of tau protein in neurodegenerative diseases is associated with post-translational modifications, which may affect the hydrophilicity, spatial conformation, and stability of tau protein, promoting tau protein aggregation and the formation of neurofibrillary tangles. Therefore, studying the role of tau protein in neurodegenerative diseases and the mechanism of aberrant aggregation is important for understanding the mechanism of neurodegenerative diseases and finding therapeutic approaches. This review describes the possible mechanisms by which tau protein promotes neurodegenerative diseases, the post-translational modifications of tau protein and associated influencing factors, and the current status of drug discovery and development related to tau protein, which may contribute to the development of new therapeutic approaches to alleviate or treat neurodegenerative diseases.

LCADNet: a novel light CNN architecture for EEG-based Alzheimer disease detection.

Alzheimer's disease (AD) is a progressive and incurable neurologi-cal disorder with a rising mortality rate, worsened by error-prone, time-intensive, and expensive clinical diagnosis methods. Automatic AD detection methods using hand-crafted Electroencephalogram (EEG) signal features lack accuracy and reliability. A lightweight convolution neural network for AD detection (LCADNet) is investigated to extract disease-specific features while reducing the detection time. The LCADNet uses two convolutional layers for extracting complex EEG features, two fully connected layers for selecting disease-specific features, and a softmax layer for predicting AD detection probability. A max-pooling layer interlaced between convolutional layers decreases the time-domain redundancy in the EEG signal. The efficiency of the LCADNet and four pre-trained models using transfer learning is compared using a publicly available AD detection dataset. The LCADNet shows the lowest computation complexity in terms of both the number of floating point operations and inference time and the highest classification performance across six measures. The generalization of the LCADNet is assessed by cross-testing it with two other publicly available AD detection datasets. It outperforms existing EEG-based AD detection methods with an accuracy of 98.50%. The LCADNet may be a valuable aid for neurologists and its Python implemen- tation can be found at github.com/SandeepSangle12/LCADNet.git.

Tau, Glial Fibrillary Acidic Protein, and Neurofilament Light Chain as Brain Protein Biomarkers in Cerebrospinal Fluid and Blood for Diagnosis of Neurobiological Diseases.

Neurological damage is the pathological substrate of permanent disability in various neurodegenerative disorders. Early detection of this damage, including its identification and quantification, is critical to preventing the disease's progression in the brain. Tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), as brain protein biomarkers, have the potential to improve diagnostic accuracy, disease monitoring, prognostic assessment, and treatment efficacy. These biomarkers are released into the cerebrospinal fluid (CSF) and blood proportionally to the degree of neuron and astrocyte damage in different neurological disorders, including stroke, traumatic brain injury, multiple sclerosis, neurodegenerative dementia, and Parkinson's disease. Here, we review how Tau, GFAP, and NfL biomarkers are detected in CSF and blood as crucial diagnostic tools, as well as the levels of these biomarkers used for differentiating a range of neurological diseases and monitoring disease progression. We also discuss a biosensor approach that allows for the real-time detection of multiple biomarkers in various neurodegenerative diseases. This combined detection system of brain protein biomarkers holds significant promise for developing more specific and accurate clinical tools that can identify the type and stage of human neurological diseases with greater precision.

The Role of Catechol in Caffeic Acid Phenethyl Ester Derivatives for Neuroprotective Effects

AbstractNeurodegenerative disorders are chronic, progressive neurological diseases characterized by damage to neuron cells. Oxidative stress and neuroinflammation play crucial roles in inducing these disorders. Caffeic acid phenethyl ester (CAPE) and its sulfone derivatives have demonstrated antioxidant and anti‐inflammatory effects, suggesting their potential as neuroprotective agents. In this study, 8 sulfone derivatives were designed and synthesized to explore the importance of catechol and structure–activity relationship of CAPE sulfone derivatives. Hydroxyl groups in catechol were replaced by ‐NO2, ‐NH2 or ‐H, and their free radical scavenging, antioxidant, and anti‐inflammatory abilities were evaluated. It was found that the antioxidant activitiy was dominated by the catechol moiety in CAPE derivatives, while the anti‐inflammtory activity was not. Furthermore, the stabilization of catechol after affording H⋅ to eliminate free radicals possibly occurred through hydrogen bond ranther than electron transfer via p‐π conjugation. After the analysis, all the target compounds lost antioxidant properties at cellular level, and among them, the target compound (E)‐2‐amino‐4‐(2‐(phenethylsulfonyl)vinyl) phenol with p‐NH2 and m‐OH showed the best free radical scavaging acivitity and retained anti‐inflammatory activity.

Investigating SNHG3 and BCYRN1 lncRnas expression in the peripheral blood cells of multiple sclerosis patients

ABSTRACT Background MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. Methods A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. Results Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02). Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). Discussion Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis.

The Impact of Pulmonary Disorders on Neurological Health (Lung-Brain Axis).

The brain and lungs, vital organs in the body, play essential roles in maintaining overall well-being and survival. These organs interact through complex and sophisticated bi-directional pathways known as the 'lung-brain axis', facilitated by their close proximity and neural connections. Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases. This review aims to delve into how pulmonary diseases, including acute/chronic airway diseases and pulmonary conditions, can instigate neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health. Ultimately, this review paves the way for exciting avenues of future research and therapeutics in addressing respiratory and neurological diseases.

Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study.

GGC repeat expansions in the NOTCH2NLC gene are associated with a broad spectrum of progressive neurologic disorders, notably, neuronal intranuclear inclusion disease (NIID). We aimed to investigate the population-wide prevalence and clinical manifestations of NOTCH2NLC-related disorders in Koreans. We conducted a study using 2 different cohorts from the Korean population. Patients with available brain MRI scans from Seoul National University Hospital (SNUH) were thoroughly reviewed, and NIID-suspected patients presenting the zigzag edging signs underwent genetic evaluation for NOTCH2NLC repeats by Cas9-mediated nanopore sequencing. In addition, we analyzed whole-genome sequencing data from 3,887 individuals in the Korea Biobank cohort to estimate the distribution of the repeat counts in Koreans and to identify putative patients with expanded alleles and neurologic phenotypes. In the SNUH cohort, among 90 adult-onset leukoencephalopathy patients with unknown etiologies, we found 20 patients with zigzag edging signs. Except for 2 diagnosed with fragile X-associated tremor/ataxia syndrome and 2 with unavailable samples, all 16 patients (17.8%) were diagnosed with NIID (repeat range: 87-217). By analyzing the Korea Biobank cohort, we estimated the distribution of repeat counts and threshold (>64) for Koreans, identifying 6 potential patients with NIID. Furthermore, long-read sequencing enabled the elucidation of transmission and epigenetic patterns of NOTCH2NLC repeats within a family affected by pediatric-onset NIID. This study presents the population-wide distribution of NOTCH2NLC repeats and the estimated prevalence of NIID in Koreans, providing valuable insights into the association between repeat counts and disease manifestations in diverse neurologic disorders.

Parkinson Disease Detection Using CNN Algorithm

Abstract: Parkinson's disease, a progressive neurological disorder, results from the depletion of dopamine-producing neurons in the brain, leading to diminished motor function. Common symptoms include tremors, rigidity, bradykinesia, shivering, and impaired balance. This study introduces two neural network architectures: the Voice Impairment Classifier, designed for early disease detection. The research conducted a thorough assessment of convolutional neural networks (CNNs) for classifying gait signals transformed into spectrogram images, and deep dense networks for analyzing voice recordings. Results demonstrated superior performance of the proposed models, with the VGFR Spectrogram Detector achieving 88.1% accuracy and the Voice Impairment Classifier achieving 89.15% accuracy, surpassing current state-of-the-art techniques.

Effects of multidisciplinary inpatient rehabilitation on everyday life physical activity and gait in patients with multiple sclerosis

BackgroundMultiple sclerosis is a progressive neurological disease that affects the central nervous system, resulting in various symptoms. Among these, impaired mobility and fatigue stand out as the most prevalent. The progressive worsening of symptoms adversely alters quality of life, social interactions and participation in activities of daily living. The main objective of this study is to bring new insights into the impact of a multidisciplinary inpatient rehabilitation on supervised walking tests, physical activity (PA) behavior and everyday gait patterns.MethodsA total of 52 patients, diagnosed with multiple sclerosis, were evaluated before and after 3 weeks of inpatient rehabilitation. Each measurement period consisted of clinical assessments and 7 days home monitoring using foot-mounted sensors. In addition, we considered two subgroups based on the Expanded Disability Status Scale (EDSS) scores: ‘mild’ (EDSS < 5) and ‘severe’ (EDSS ≥ 5) disability levels.ResultsSignificant improvements in fatigue, quality of life and perceived mobility were reported. In addition, walking capacity, as assessed by the 10-m walking test, two-minute walk test and timed-up-and-go test, improved significantly after rehabilitation. Regarding the home assessment, mildly disabled patients significantly increased their locomotion per day and complexity of daily PA pattern after rehabilitation, while severely disabled patients did not significantly change. There were distinct and significant differences in gait metrics (i.e., gait speed, stride length, cadence) between mildly and severely disabled patients, but the statistical models did not show a significant overall rehabilitation effect on these gait metrics.ConclusionInpatient rehabilitation showed beneficial effects on self-reported mobility, self-rated health questionnaires, and walking capacity in both mildly and severely disabled patients. However, these improvements do not necessarily translate to home performance in severely disabled patients, or only marginally in mildly disabled patients. Motivational and behavioral factors should also be considered and incorporated into treatment strategies.

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer's Dementia: Clinical Trial Systematic Review.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Advances in the application of fecal microbiota transplantation for the treatment of nervous system diseases

The intestinal microbiota exhibits a strong correlation with the function of the central nervous system, exerting influence on the host brain through neural pathways, immune pathways, and microbial metabolites along the gut-brain axis. Disorders in the composition of the intestinal microbial are closely associated with the onset and progression of neurological disorders, such as depression, Alzheimer's disease, and Parkinson's disease. It has been proven that fecal microbiota transplantation can improve symptoms in animal models of neurological diseases and clinical patients. This paper provides a comprehensive review of the composition and function of the human intestinal microbiota, as well as the intricate the relationship between the human intestinal microbiota and nervous system diseases through the gut-brain axis. Additionally, it delves into the research advancements and underlying mechanism of fecal microbiota transplantation in the treatment of nervous system diseases. These findings offer novel insights and potential avenues for clinical interventions targeting nervous system diseases.

Neuropathological evidence for neurosarcoidosis is more widespread than imaging suggests.

We present a single case of a 47year old male with a relapsing progressive neurological disease characterised by an infiltrative inflammation of the brain and leptomeninges. Investigations revealed the presence of systemic sarcoidosis which was confirmed histologically following a mediastinal lymph node biopsy. The imaging appearances of the brain and spinal canal lesions were compatible with neurological involvement by the same disease. Despite treatment, the patient deteriorated and died. We present the neuropathological findings, correlate these with the imaging features, and find that neuropathological evidence for disease was in this case strikingly more widespread than predicted by imaging ante-mortem.

Evaluation of Neuroprotective effect of Cassia occidentalis L. against Colchicine Induced Memory Impairment in Wistar Rats

Background: Alzheimer’s disease (AD) is a progressive neurological disorder that develops with aging. Objective: In this research, we have examined the anti - Alzheimer’s effect of ethanolic extract from roots of Cassia occidentalis L. on colchicine-induced Alzheimer’s in Wistar rats Methods: Ethanolic extract was obtained and spectroscopic, chromatography analysis was performed. Acute toxicity studies using Organization of Economic Co-operation and Development (OECD) Guidelines 423 were performed to examine and make sure that there were no signs of toxic effects. The induction of AD was done using colchicine which leads to symptoms like neurotoxicity, neuroinflammation, and neurodegeneration. In this experiment, a thorough analysis of body weight, behavioral parameters, locomotor activity, and biochemical evaluation was performed to estimate the medicinal properties of Cassia occidentalis L in treating Alzheimer’s disease. Results: Pharmacognostic analysis showed the presence of vascular bundles, starch grains, fibers, calcium oxalate crystals, elongated parenchyma, and collenchyma mucilage as shown in the supplementary files. Locomotor activity, Escape latency time, Conditioned avoidance response, and Transfer latency were improved with treatment. Interleukin- 6 (IL - 6) levels were reduced significantly in the Colchicine + 200 Cassia mg/kg group (739.2 ± 0.37 pg/ml) than in the Colchicine Group (850.6±0.40 pg/ml). Tumor necrosis factor (TNF-α) was decreased in the Colchicine + 200 Cassia mg/kg Group (1030.93±0.51 pg/ml) than in the Colchicine Group (1455.06±1.25 pg/ml). A significant decrease in total protein level was observed in the Colchicine Group (2.52±0.10 mg/ml), (3.33±0.90 mg/ml) as compared to Colchicine + 200 Cassia mg/kg Group (5.27±0.09 mg/ml, (5.01±0.10 mg/ml) respectively, in the Hippocampus and Entorhinal cortex. The levels of antioxidant enzymes such as Catalase (CAT), Serum superoxide dismutase (SOD), Reduced glutathione (GSH) and Malondialdehyde (MDA) were measured. When compared to the Colchicine Group (7.33±0.16 nM/ mg, the MDA level was lower in the Colchicine + 100 Cassia mg/kg Group (3.20±0.01 nM/ mg). The level of CAT in Colchicine + 200 Cassia mg/kg Group (7.01±0.03 μmoles of H2O2/mg of protein) was seen to be increased when compared to Colchicine Group (3.32 ± 0.17 μmoles of H2O2/mg of protein). The level of SOD in Colchicine + 200 Cassia mg/kg Group (7.43±0.02 U mg -1 of protein) was seen to be increased when compared with Colchicine Group (4.55±0.03 U mg -1 of protein). The level of GSH in Colchicine + 200 Cassia mg/kg Group (10.07±0.19 nM/mg -1 of protein) was increased when compared with the Colchicine Group (5.82±0.11nM/mg -1 of protein). Histopathology of the Hippocampus and Entorhinal cortex showed diminished amyloid plaques, and neurodegeneration in the treatment groups Conclusion: The present study showed that ethanolic extract from the roots of Cassia occidentalis L. At 100 and 200 mg/kg doses in Wistar rats improved memory damage, by reducing oxidative stress. Levels of the antioxidant enzymes as CAT, and SOD, GSH were increased and MDA was decreased. The cytokine levels in the serum of Wistar rats of IL-6 level and TNF-α level were reduced significantly. Estimation of total protein level was found to be increased. It restored neuronal degeneration in the Hippocampus, and Entorhinal cortex and reduced oxidative stress. This suggests that the ethanolic extract of Cassia occidentalis L. could be an effective therapeutic treatment for neurodegenerative diseases like AD.

Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases.