Treatment Of Neurological Disorders Research Articles

Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases

Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson’s disease, Charcot–Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.

Innovative applications of nanotechnology in neuroscience and brain-computer interfaces

The innovative application of nanotechnology in neuroscience and brain-computer interfaces is running a revolutionary revolution. By precisely controlling ministerial size, shape and surface properties, scientists have designed highly compatible nanomaterials with neural cells and show great potential in accurately recording and stimulating neural signals and the regeneration and repair of neural tissue. These innovative applications not only improve our cognition and understanding of the nervous system but also offer new strategies and tools for the treatment of neurological diseases. The application of nanotechnology in neuroscience and brain-computer interfaces also faces challenges in biocompatibility, safety, long-term effects, and cost. In the future, with the continuous progress of technology and the deepening of interdisciplinary research, we have reason to believe that nanotechnology will play a more important role in the interface of neuroscience and brain-computer, and make a greater contribution to the cause of human health. This paper reviews the latest research achievements and technological progress in this field, prospects for its future trends and identifies the challenges and research directions to follow.

Alkaloid-rich fraction from Luffa cylindrica Linn fruit enhances memory and mitigates oxidative stress in hippocampus of ozone-exposed sprague Dawley rat via LCMS and network pharmacology approach.

Luffa cylindrica (L.), is a medicinal plant aimed to investigate the efficacy of the alkaloid-rich fraction (ARF) extracted from L. cylindrica. The study employed behavioural analysis of rat using Morris water maze (MWM), biochemical analysis of apoptotic proteins, Immunohistochemistry of caspase 3 protein and network pharmacology approach. The ozone-induced group exhibited complex behavioral changes. Western blot analysis revealed altered expression of SOD2, Caspase 3, and Cytochrome C which play integral roles in oxidative stress, apoptosis, and mitochondrial function. Histopathological analysis of the hippocampus further supported the neuroprotective potential of L. cylindrica, demonstrating a reduction in neuropathological lesions and improved memory processes. Network Pharmacology showed the implication of GSK3β in neuronal damage. ARF showed promise in preventing further neuronal damage. In summary, this comprehensive study sheds light on its potential in neuroprotective applications by in vivo behavioral and molecular analyses. It provides a holistic understanding of the medicinal properties of ARF, encouraging further exploration for potential therapeutic interventions in neurological diseases.

Understanding the intricacies of cellular mechanisms in remyelination: The role of circadian rhythm.

The term "circadian rhythm" refers to the 24-h oscillations found in various physiological processes in organisms, responsible for maintaining bodily homeostasis. Many neurological diseases mainly involve the process of demyelination, and remyelination is crucial for the treatment of neurological diseases. Current research mainly focuses on the key role of circadian clocks in the pathophysiological mechanisms of multiple sclerosis. Various studies have shown that the circadian rhythm regulates various cellular molecular mechanisms and signaling pathways involved in remyelination. The process of remyelination is primarily mediated by oligodendrocyte precursor cells (OPCs), oligodendrocytes, microglia, and astrocytes. OPCs are activated, proliferate, migrate, and ultimately differentiate into oligodendrocytes after demyelination, involving many key signaling pathway and regulatory factors. Activated microglia secretes important cytokines and chemokines, promoting OPC proliferation and differentiation, and phagocytoses myelin debris that inhibits remyelination. Astrocytes play a crucial role in supporting remyelination by secreting signals that promote remyelination or facilitate the phagocytosis of myelin debris by microglia. Additionally, cell-to-cell communication via gap junctions allows for intimate contact between astrocytes and oligodendrocytes, providing metabolic support for oligodendrocytes. Therefore, gaining a deeper understanding of the mechanisms and molecular pathways of the circadian rhythm at various stages of remyelination can help elucidate the fundamental characteristics of remyelination and provide insights into treating demyelinating disorders.

Natural Products in the Treatment of Neurological Diseases (Part 2): Host-Guest Complexes

Permeation through the blood-brain barrier is one issue that should be supplanted to develop novel drugs to treat brain disorders. Host-guest complexes involving cyclodextrins, cucurbiturils, and calixarenes are promissory structures to tackle this problem. This paper shows the desired properties of the inclusion complexes involving natural products and how they can be used to develop new treatments for brain disease.

Enhanced neurological anomaly detection in MRI images using deep convolutional neural networks.

Neurodegenerative diseases, including Parkinson's, Alzheimer's, and epilepsy, pose significant diagnostic and treatment challenges due to their complexity and the gradual degeneration of central nervous system structures. This study introduces a deep learning framework designed to automate neuro-diagnostics, addressing the limitations of current manual interpretation methods, which are often time-consuming and prone to variability. We propose a specialized deep convolutional neural network (DCNN) framework aimed at detecting and classifying neurological anomalies in MRI data. Our approach incorporates key preprocessing techniques, such as reducing noise and normalizing image intensity in MRI scans, alongside an optimized model architecture. The model employs Rectified Linear Unit (ReLU) activation functions, the Adam optimizer, and a random search strategy to fine-tune hyper-parameters like learning rate, batch size, and the number of neurons in fully connected layers. To ensure reliability and broad applicability, cross-fold validation was used. Our DCNN achieved a remarkable classification accuracy of 98.44%, surpassing well-known models such as ResNet-50 and AlexNet when evaluated on a comprehensive MRI dataset. Moreover, performance metrics such as precision, recall, and F1-score were calculated separately, confirming the robustness and efficiency of our model across various evaluation criteria. Statistical analyses, including ANOVA and t-tests, further validated the significance of the performance improvements observed with our proposed method. This model represents an important step toward creating a fully automated system for diagnosing and planning treatment for neurological diseases. The high accuracy of our framework highlights its potential to improve diagnostic workflows by enabling precise detection, tracking disease progression, and supporting personalized treatment strategies. While the results are promising, further research is necessary to assess how the model performs across different clinical scenarios. Future studies could focus on integrating additional data types, such as longitudinal imaging and multimodal techniques, to further enhance diagnostic accuracy and clinical utility. These findings mark a significant advancement in applying deep learning to neuro-diagnostics, with promising implications for improving patient outcomes and clinical practices.

CLINICAL CASE OF CONNECTIVE TISSUE AND NEURODEGENERATIVE DISEASE

We present a patient with 5 years Systemic lupus erythematodes (SLE), antiphospholipid syndrome (APS), dementia the type of Alzheimer and clininical symptoms of neurodegenerative disease (Parcinson's). The history of patient proceeds with progression and overlap of clinical characteristics of systemic and neurodegenerative disease. Combined treatment for systhemic and neurological disease is important for clinical improvement of these patients.

Drug Delivery Across the Blood-Brain Barrier: A New Strategy for the Treatment of Neurological Diseases.

The blood-brain barrier (BBB) serves as a highly selective barrier between the blood and the central nervous system (CNS), and its main function is to protect the brain from foreign substances. This physiological property plays a crucial role in maintaining CNS homeostasis, but at the same time greatly limits the delivery of drug molecules to the CNS, thus posing a major challenge for the treatment of neurological diseases. Given that the high incidence and low cure rate of neurological diseases have become a global public health problem, the development of effective BBB penetration technologies is important for enhancing the efficiency of CNS drug delivery, reducing systemic toxicity, and improving the therapeutic outcomes of neurological diseases. This review describes the physiological and pathological properties of the BBB, as well as the current challenges of trans-BBB drug delivery, detailing the structural basis of the BBB and its role in CNS protection. Secondly, this paper reviews the drug delivery strategies for the BBB in recent years, including physical, biological and chemical approaches, as well as nanoparticle-based delivery technologies, and provides a comprehensive assessment of the effectiveness, advantages and limitations of these delivery strategies. It is hoped that the review in this paper will provide valuable references and inspiration for future researchers in therapeutic studies of neurological diseases.

Brain-Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs.

Bidirectional communication between the central nervous system (CNS) and peripheral organs and tissue has been widely documented in physiological and pathological conditions. This communication relies on the bilateral transmission of signaling molecules and substances that circulate throughout the body and reach their target site(s) via the blood and other biological fluids (e.g., the cerebrospinal fluid, the lymph). One of the mechanisms by which these molecular messengers are exchanged is through the secretion of extracellular vesicles (EVs). EVs are known to mediate cell-to-cell communication by delivering biological molecules, including nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood-brain barrier (BBB), enabling direct communication between the periphery and the brain. In particular, the delivery of microRNAs (miRNAs) can modulate the expression profiles of recipient cells, thereby influencing their functions. This review synthesizes current findings about the brain-periphery cross-talk mediated by EVs-delivered miRNAs. Although this mechanism has been definitively shown in a few cases, much evidence indirectly indicates that it could mediate brain-peripherical organs/tissue communication, especially in pathological conditions. Therefore, understanding this process could provide valuable insights for the treatment and management of neurological and systemic diseases.

Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities.

Glial cell polarization plays a pivotal role in various neurological disorders. In response to distinct stimuli, glial cells undergo polarization to either mitigate neurotoxicity or facilitate neural repair following injury, underscoring the importance of glial phenotypic polarization in modulating central nervous system function. This review presents an overview of glial cell polarization, focusing on astrocytes and microglia. It explores the involvement of glial polarization in neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis and meningoencephalitis. Specifically, it emphasizes the role of glial cell polarization in disease pathogenesis through mechanisms including neuroinflammation, neurodegeneration, calcium signaling dysregulation, synaptic dysfunction and immune response. Additionally, it summarizes various therapeutic strategies including pharmacological treatments, dietary supplements and cell-based therapies, aimed at modulating glial cell polarization to ameliorate brain dysfunction. Future research focused on the spatio-temporal manipulation of glial polarization holds promise for advancing precision diagnosis and treatment of neurological diseases.

Gold Nanoparticles Decorated CoAl LDH Monolayer: A Peroxidase-Like Nanozyme for Sensitive Colorimetric Detection of Acetylcholinesterase and Inhibitors.

Monitoring acetylcholinesterase (AChE) activity and its inhibitor is crucial yet challenging for the early diagnosis and treatment of neurological diseases. In this study, we present Au nanoparticle decorated CoAl layered double hydroxide monolayer (Au@CoAl-LDH-m) as a peroxidase-like (POD) nanozyme for the sensitive colorimetric detection of AChE and its inhibitor, thiamine pyrophosphate (TPP). Remarkably, the Au@CoAl-LDH-m nanozyme can catalyze the oxidation of chromogenic substrates through its POD-like activity, which is effectively inhibited by thiocholine (TCh, a catalytic product of AChE), thereby enabling detection of AChE and TPP through a visible colorimetric readout. The approach provides a highly sensitive and specificity assay with a broader linear response range (1-100 mU mL-1 for AChE and 1-1000 ng mL-1 for TPP) and a low detection limit (0.092 mU mL-1 for AChE and 0.201 ng mL-1 for TPP), respectively. These results highlight the significant potential of Au@CoAl-LDH-m for advancing colorimetric sensors in detecting small molecules across various biological applications.

Tensor dictionary-based heterogeneous transfer learning to study emotion-related gender differences in brain

In practice, collecting auxiliary labeled data with same feature space from multiple domains is difficult. Thus, we focus on the heterogeneous transfer learning to address the problem of insufficient sample sizes in neuroimaging. Viewing subjects, time, and features as dimensions, brain activation and dynamic functional connectivity data can be treated as high-order heterogeneous data with heterogeneity arising from distinct feature space. To use the heterogeneous priori knowledge from the low-dimensional brain activation data to improve the classification performance of high-dimensional dynamic functional connectivity data, we propose a tensor dictionary-based heterogeneous transfer learning framework. It combines supervised tensor dictionary learning with heterogeneous transfer learning for enhance high-order heterogeneous knowledge sharing. The former can encode the underlying discriminative features in high-order data into dictionaries, while the latter can transfer heterogeneous knowledge encoded in dictionaries through feature transformation derived from mathematical relationship between domains. The primary focus of this paper is gender classification using fMRI data to identify emotion-related brain gender differences during adolescence. Additionally, experiments on simulated data and EEG data are included to demonstrate the generalizability of the proposed method. Experimental results indicate that incorporating prior knowledge significantly enhances classification performance. Further analysis of brain gender differences suggests that temporal variability in brain activity explains differences in emotion regulation strategies between genders. By adopting the heterogeneous knowledge sharing strategy, the proposed framework can capture the multifaceted characteristics of the brain, improve the generalization of the model, and reduce training costs. Understanding the gender specific neural mechanisms of emotional cognition helps to develop the gender-specific treatments for neurological diseases.

Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats

Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.

Naringenin Nanoformulations for Neurodegenerative Diseases.

Glioblastoma (GBM) is a grade-IV astrocytoma, which is the most common and aggressive type of brain tumor, spreads rapidly and has a life-threatening catastrophic effect. GBM mostly occurs in adults with an average survival time of 15 to 18 months, and the overall mortality rate is 5%. Significant invasion and drug resistance activity cause the poor diagnosis of GBM. Naringenin (NRG) is a plant secondary metabolite byproduct of the flavanone subgroup. NRG can cross the blood-brain barrier and deliver drugs into the central nervous system when conjugated with appropriate nanocarriers to overcome the challenges associated with gliomas through naringenin-loaded nanoformulations. Here, we discuss several nanocarriers employed that are as delivery systems, such as polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions. These naringenin-loaded nanoformulations have been tested in various in vitro and in vivo models as a potential treatment for brain disorders. This review nanoformulations of NRG can a possible therapeutic alternative for the treatment of neurological diseases are discussed.

Isolation and Culturing of Primary Neurons from Newborn Mouse Cortex Tissue

Objective: This study aimed to establish a reliable protocol for obtaining healthy and long-lived cortical neurons from newborn mice, providing a valuable model for studying neuronal function. Materials and Methods: Cortical regions of P0 mice were isolated and healthy neurons were obtained by enzymatic and mechanical dissociation. On the seventh day of incubation, the presence of neurons was detected by staining with neuron-specific antibodies. Transgenic mice expressing fluorescent proteins specific to neurons, glia and oligodendrocytes were also used for culture. Results: Almost all the neurons had adhered to the petri dish bottom by the second hour of incubation. Most of the neurons were healthy and started to grow extension quickly. Conclusion: Neuron cultures are an important tool in research and are invaluable for studying the behaviour of cells. Nanoparticles facilitate genetic manipulation of these cultures for various biotechnological applications. In particular, they have great potential in areas such as the delivery of genetic material into cells, drug delivery and targeted treatment methods. Such techniques have the potential to open up new avenues for the study and treatment of neurological diseases.

Ultrasound-Triggered NO Release to Promote Axonal Regeneration for Noise-Induced Hearing Loss Therapy.

Intense noise poses a threat to spiral ganglion neurons (SGNs) in the inner ear, often resulting in limited axonal regeneration during noise injury and leading to noise-induced hearing loss (NIHL). Here, we propose an ultrasound-triggered nitric oxide (NO) release to enhance the sprouting and regeneration of injured axons in SGNs. We developed hollow silicon nanoparticles to load nitrosylated N-acetylcysteine, producing HMSN-SNO, which effectively protects NO from external interferences. Utilizing low-intensity ultrasound stimulation with bone penetration, we achieve the controlled release of NO from HMSN-SNO within the cochlea. In mice with NIHL, a rapid and extensive loss of synaptic connections between hair cells and SGNs is observed within 24 h after exposure to excessive noise. However, this loss could be reversed with the combined treatment, resulting in a hearing functional recovery from 83.57 to 65.00 dB SPL. This positive outcome is attributed to the multifunctional effects of HMSN-SNO, wherein they scavenge reactive oxygen species (ROS) to reverse the pathological microenvironment and simultaneously upregulate the CREB/BDNF/EGR1 signaling pathway, thereby enhancing neuroplasticity and promoting the regeneration of neuronal axons. These findings underscore the potential of nanomedicine for neuroplasticity modulation, which holds promise for advancing both basic research and the further treatment of neurological diseases.

Murine model of minimally invasive nasal depot (MIND) technique for central nervous system delivery of blood-brain barrier-impermeant therapeutics.

The blood-brain barrier (BBB) poses a substantial obstacle to the successful delivery of therapeutics to the central nervous system (CNS). The transnasal route has been extensively explored, but success rates have been modest due to challenges related to the precise anatomical placement of drugs, the small volumes that the olfactory cleft can accommodate and short drug residence times due to mucociliary clearance. Here, to address these issues, we have developed a surgical technique known as the minimally invasive nasal depot (MIND), which allows the accurate placement of depot drugs into the submucosal space of the olfactory epithelium of rats. This technique exploits the unique anatomy of the olfactory apparatus to enable transnasal delivery of drugs into the CNS, bypassing the BBB. In our rat model, a bony window is created in the animal snout to expose the submucosal space. Using the MIND technique, we have successfully delivered oligonucleotides to the CNS in Sprague-Dawley and Long-Evans rats, leading to an upregulation of brain-derived neurotrophic factor in the substantia nigra and hippocampus. In this Protocol, we describe the procedural steps for MIND. This procedure takes about 45 min and can be performed by researchers with basic surgical skills. We additionally describe modifications to perform MIND in mice, which are anatomically smaller. The MIND procedure represents a unique platform that can be used to overcome the limitations posed by the BBB. This technique can potentially expand the therapeutic toolkit in the treatment of neurological diseases.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases.

The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

Frontal Horn of Lateral Ventricle of Brain and Its Relation with Age, Gender and Side: Morphometric Study by Computed Tomography among Bangladeshi Population

Background: Knowledge of the baseline reference value of frontal horn size is necessary for the initial and precise analysis of ventriculomegaly. The purpose of this study was to determine the size of frontal horn of lateral ventricle and its relation with age, gender and side among adult Bangladeshi population of Chattogram district. Materials and methods: This cross-sectional analytical study was conducted during the period from July 2022 to June 2023 in the Department of Anatomy, Chittagong Medical College, Chattogram, upon 150 respondents of 20-60 years who had normal Computed Tomography (CT) scans as reported by an expert radiologist. For statistical analysis, Mann-Whitney U test, Wilcoxon signed rank test and ANOVA test were done. p-value was considered significant if it was <0.05 at 95% level of confidence. Results: The mean right and left frontal horn length was 25.50 (±3.95) mm and 25.28 (±4.04) mm respectively. The length of the frontal horn of both right and left sided lateral ventricle were significantly higher in male than that of female (p<0.01). Spearman's correlation coefficient indicated positive linear correlation of length of frontal horn (Right and left side) with age, insignificant in right side (p=0.061) but significant in left side (p=0.046). Conclusion: Morphometric analysis of the frontal horn of the lateral ventricles among the Bangladeshi population produced a number of significant results that may help with the early diagnosis and treatment of neurological diseases that are particular to gender and age. These findings can be validated and expanded upon in future research using bigger sample sizes and cutting-edge imaging methods. IAHS Medical Journal Vol 7(1), June 2024; 54-59

Navigating the nano-bio immune interface: advancements and challenges in CNS nanotherapeutics.

In recent years, significant advancements have been made in utilizing nanoparticles (NPs) to modulate immune responses within the central nervous system (CNS), offering new opportunities for nanotherapeutic interventions in neurological disorders. NPs can serve as carriers for immunomodulatory agents or platforms for delivering nucleic acid-based therapeutics to regulate gene expression and modulate immune responses. Several studies have demonstrated the efficacy of NP-mediated immune modulation in preclinical models of neurological diseases, including multiple sclerosis, stroke, Alzheimer's disease, and Parkinson's disease. While challenges remain, advancements in NPs engineering and design have led to the development of NPs using diverse strategies to overcome these challenges. The nano-bio interface with the immune system is key in the conceptualization of NPs to efficiently act as nanotherapeutics in the CNS. The biomolecular corona plays a pivotal role in dictating NPs behavior and immune recognition within the CNS, giving researchers the opportunity to optimize NPs design and surface modifications to minimize immunogenicity and enhance biocompatibility. Here, we review how NPs interact with the CNS immune system, focusing on immunosurveillance of NPs, NP-induced immune reprogramming and the impact of the biomolecular corona on NPs behavior in CNS immune responses. The integration of NPs into CNS nanotherapeutics offers promising opportunities for addressing the complex challenges of acute and chronic neurological conditions and pathologies, also in the context of preventive and rehabilitative medicine. By harnessing the nano-bio immune interface and understanding the significance of the biomolecular corona, researchers can develop targeted, safe, and effective nanotherapeutic interventions for a wide range of CNS disorders to improve treatment and rehabilitation. These advancements have the potential to revolutionize the treatment landscape of neurological diseases, offering promising solutions for improved patient care and quality of life in the future.