Management Of Neurological Disorders Research Articles

Digirseophene A promotes recovery in injured developing cerebellum via AMPK/AKT/GSK3β pathway-mediated neural stem cell proliferation

Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3β inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3β pathway.

Exploring Therapeutic Frontiers: Unveiling the Potential of Natural Diterpenoid Derivatives in Addressing Neurological Disorders.

Neurological disorders present a formidable challenge in healthcare, necessitating the continuous exploration of innovative therapeutic avenues. This review delves into the burgeoning field of natural diterpenoid derivatives and their promising role in addressing neurological disorders. Derived from natural sources, these compounds exhibit a diverse range of pharmacological properties, positioning them as potential agents for treating conditions such as Alzheimer's and Parkinson's disease. The review highlights recent advancements, shedding light on the multifaceted mechanisms through which diterpenoid derivatives exert their effects, from antiinflammatory to neuroprotective actions. As the scientific community navigates the translational journey from bench to bedside, integrating these natural compounds into neurotherapeutics emerges as a compelling prospect. This exploration of the therapeutic frontiers of natural diterpenoid derivatives signifies a significant step towards innovative and effective strategies in the management of neurological disorders. It highlights the potential of natural compounds to revolutionize neurotherapeutics.

Artificial Intelligence in Neurology: Current Applications and Future Prospects

Artificial intelligence (AI) is reshaping the field of neurology, enhancing diagnosis, treatment, and management of neurological disorders. This article explores AI's role in neurology, highlighting its ability to process vast amounts of data to improve diagnostic accuracy and personalize treatments. AI applications, from neuroimaging to clinical decision support, have shown promising results in enhancing patient care. However, challenges such as data security, ethical concerns, and the need for stringent regulatory frameworks remain significant. The potential of AI in neurology continues to grow, promising revolutionary changes in patient outcomes and healthcare practices, provided these challenges are effectively managed.

Flexible Peripheral Nerve Interfacing Electrode for Joint Position Control in Closed-Loop Neuromuscular Stimulation.

Addressing peripheral nerve disorders with electronic medicine poses significant challenges, especially in replicating the dynamic mechanical properties of nerves and understanding their functionality. In the field of electronic medicine, it is crucial to design a system that thoroughly understands the functions of the nervous system and ensures a stable interface with nervous tissue, facilitating autonomous neural adaptation. Herein, we present a novel neural interface platform that modulates the peripheral nervous system using flexible nerve electrodes and advanced neuromodulation techniques. Specifically, we have developed a surface-based inverse recruitment model for effective joint position control via direct electrical nerve stimulation. Utilizing barycentric coordinates, this model constructs a three-dimensional framework that accurately interpolates inverse isometric recruitment values across various joint positions, thereby enhancing control stability during stimulation. Experimental results from rabbit ankle joint control trials demonstrate our model's effectiveness. In combination with a proportional-integral-derivative (PID) controller, it shows superior performance by achieving reduced settling time (less than 1.63 s), faster rising time (less than 0.39 s), and smaller steady-state error (less than 3 degrees) compared to the legacy model. Moreover, the model's compatibility with recent advances in flexible interfacing technologies and its integration into a closed-loop controlled functional neuromuscular stimulation (FNS) system highlight its potential for precise neuroprosthetic applications in joint position control. This approach marks a significant advancement in the management of neurological disorders with advanced neuroprosthetic solutions.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

Europinidin Mitigates 3-NPA-Induced Huntington's Disease Symptoms in Rats: A Comprehensive Analysis of Oxidative Stress, Mitochondrial Enzyme Complex Activity, Pro-Inflammatory Markers and Neurotransmitter Alterations.

Huntington's disease (HD) is a neurodegenerative disease that causes progressive motor and cognitive dysfunction. There is no cure for HD, and current therapeutics can only manage the signs and symptoms as well as slowing disease progression. This investigation examines the possible therapeutic advantages of europinidin in 3-nitropropionic acid (3-NPA) injected HD in rats. Wistar rats were randomly assigned to five groups (n = 6): normal control, 3-NPA (10 mg/kg, i.p.), 3-NPA + europinidin-10 (10 mg/kg, p.o.), 3-NPA + europinidin-20 (20 mg/kg, p.o.), and europinidin alone (20 mg/kg, p.o.) for 15-day. Various behavioral and biochemical parameters including antioxidant levels, oxidative stress, pro-inflammatory markers, mitochondrial enzyme complex, and neurotransmitters were assessed. Europinidin restored biochemical, mitochondrial dysfunction, oxidative stress, neurotransmitter, and pro-inflammatory parameters disrupted by 3-NPA. Here we show that europinidin attenuates 3-NPA-induced neurodegeneration in rat models of HD. Europinidin modulates oxidative stress, enhances antioxidants, restores mitochondrial enzyme complex activity, reduces neuroinflammation, and modulates neurotransmitter levels. Our findings reveal the potential of europinidin as a novel therapeutic agent for the treatment of HD. This study also provides new insights into the molecular mechanisms of europinidin-mediated neuroprotection and may have a beneficial role in the management of neurological diseases.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

Therapeutic potential of vasopressin in the treatment of neurological disorders

Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.

Polarity directed solvent extracts from Bukiniczia Cabulica (Boiss.) Lincz. ameliorate scopolamine induced amnesia: HPLC-DAD polyphenolics analysis, cholinesterase, COX2, BACE1 inhibitory, anti-amyloid, antioxidant, molecular docking and behavioral correlates

Medicinal plants and polyphenolics of the family Plumbaginaceae have ethnomedicinal relevance in the management of neurological disorders. The current study was aimed to assess protective potentials of Bukiniczia cabulica (Boiss.) Lincz. against scopolamine induced amnesia. Quantitative polyphenolics assessment of the crude extract (Bc.Cme) was performed using HPLC-DAD analysis. In vitro cholinesterase (AChE/BChE), cyclooxygenase-2 (COX2) inhibitory and antioxidant (DPPH/ABTS) studies were performed following standard protocols. Spatial memory and neurocognitive benefits of the samples were tested in amnesic animals using Shallow Water Maze (SWM), Elevated Plus Maze (EPM), Y-Maze paradigms. The BACE1 inhibitory and anti-amyloid (Aβ) studies were performed using western blotting technique in amnesic animals. Binding affinity of the identified compounds against the target enzymes were evaluated via MOE software. A total of thirteen bioactive polyphenols including syringic acid (129.9 ± 0.9 mg/g), 4-Caffeoylquinic Acid (67.6 ± 0.3 mg/g), qurecetin-3-O-rutinoside (33.6 ± 0.5 mg/g), quercetin-3-feruloyl sophoroside (16.9 ± 0.3 mg/g), quercetin pentosyl hexoside (14.0 ± 0.3 mg/g), isorhamnetin-3-caffeoyl-7-glucoside (15.6 ± 0.5 mg/g), quercetin-3-(p-coumaroyl diglucoside)-7-glucoside (11.8 ± 0.3 mg/g), procyanidin trimer (10 ± 0.2 mg/g), were quantified. The Bc.Cme was found highly active against both AChE/BChE with IC50 values of 23.1 and 42.62 ug/ml respectively. In a DPPH and ABTS radical scavenging assay Bc.Cme considerable radicals scavenging activity. Further, Bc.Cme effectively inhibited COX-2 enzyme with IC50 value of 74.3 ug/ml. The Bc.Cme offered protection against scopolamine induced amnesia in various behavioral models. The BACE1 enzyme was inhibited significantly as compared to amnesia group animals and a considerable decline in Aβ load was observed in Bc.Cme treated animals. Affinity was observed for the identified compounds against target enzymes.

Active Compounds of Panax ginseng in the Improvement of Alzheimer's Disease and Application of Spatial Metabolomics.

Panax ginseng C.A. Meyer (P. ginseng) is one of the more common traditional Chinese medicines (TCMs). It contains numerous chemical components and exhibits a range of pharmacological effects. An enormous burden is placed on people's health and life by Alzheimer's disease (AD), a neurodegenerative condition. Recent research has shown that P. ginseng's chemical constituents, particularly ginsenosides, have a significant beneficial impact on the prevention and management of neurological disorders. To understand the current status of research on P. ginseng to improve AD, this paper discusses the composition of P. ginseng, its mechanism of action, and its clinical application. The pathogenesis of AD includes amyloid beta protein (Aβ) generation and aggregation, tau protein hyperphosphorylation, oxidant stress, neuroinflammation, mitochondrial damage, and neurotransmitter and gut microbiota disorders. This review presents the key molecular mechanisms and signaling pathways of the active ingredients in P. ginseng involved in improving AD from the perspective of AD pathogenesis. A P. ginseng-related signaling pathway network was constructed to provide effective targets for the treatment of AD. In addition, the application of spatial metabolomics techniques in studying P. ginseng and AD is discussed. In summary, this paper discusses research perspectives for the study of P. ginseng in the treatment of AD, including a systematic and in-depth review of the mechanisms of action of the active substances in P. ginseng, and evaluates the feasibility of applying spatial metabolomics in the study of AD pathogenesis and pharmacological treatment.

Current non-invasive strategies for brain drug delivery: overcoming blood-brain barrier transport.

The blood-brain barrier (BBB) is a complex and dynamic structure that serves as a gatekeeper, restricting the migrations of most compounds and molecules from blood into the central nervous system (CNS). The BBB plays a crucial role in maintaining CNS physiological function and brain homeostasis. It can protect the CNS from the entrance of toxic and infectious agents, however, it also restricts the drug permeation into brain to play a therapeutic role. The BBB has been the biggest limiting hurdle to medications entering the brain excluding from the brain about 100% of large-molecule and more than 98% of all small-molecule neurotherapeutics. As a result, it is of inability for drug molecule to reach requisite concentrations within the brain. With the aim of enhancing drug permeability and efficacy, a variety of strategies have been developed: invasive approaches, such as intraarterial delivery, intrathecal delivery, or administrating directly the drug intraventricularly and intracerebrally; non-invasive approaches that take advantage of innate BBB functions, using prodrugs, focused ultrasound, intranasal administration or nanotechnology. Here we mainly review recent developments and challenges related to non-invasive BBB-crossing techniques, whose benefits include higher efficacy, easier application, less treatment burden, better patient acceptability, and adherence. Additionally, we also analyze the potential of non-invasive methods in the treatment of CNS disorders and render them as a most suitable platform for the management of neurological diseases.

Revolutionizing Imaging and Diagnostics: Harnessing Metallic Nanoparticles and Nanocarriers for Cutting-Edge Theranostics

The field of medical diagnostics and therapeutics is currently undergoing a transformative revolution, driven by the rapid advancements in nanotechnology. This paper explores the promising potential of metallic nanoparticles and nanocarriers in the realm of theranostics, a fusion of therapy and diagnostics, offering unprecedented opportunities for precision medicine and patient care. The integration of metallic nanoparticles and nanocarriers into medical applications has opened new frontiers for non-invasive imaging and targeted therapy. This review provides an in-depth analysis of metallic nanoparticles, including gold, silver, and magnetic nanoparticles, highlighting their unique physicochemical properties that make them ideal candidates for imaging and therapeutic purposes. Additionally, we discuss the evolution of nanocarriers, such as liposomes, micelles, and dendrimers, and their role in enhancing drug delivery, bioavailability, and treatment specificity. The versatility of metallic nanoparticles and nanocarriers in both imaging and therapeutic applications is showcased through their utilization in areas such as cancer diagnosis, drug delivery, and the management of neurological disorders. Furthermore, their potential to enable real-time monitoring of treatment responses and disease progression is explored, empowering clinicians with essential tools for personalized medicine. Challenges and considerations related to toxicity, biocompatibility, and regulatory hurdles are also discussed, shedding light on the need for further research and collaboration between scientists, clinicians, and regulatory bodies. As metallic nanoparticles and nanocarriers continue to evolve, they promise to revolutionize the landscape of medical diagnostics and therapy, ultimately improving patient outcomes and enhancing the effectiveness of healthcare practices. This paper serves as a comprehensive overview of the current state and future prospects of these groundbreaking technologies, contributing to the advancement of theranostics and its wide-reaching implications for the healthcare industry.

Prediction of incidence of neurological disorders in HIV-infected persons in Taiwan: a nested case–control study

BackgroundNeurological disorders are still prevalent in HIV-infected people. We aimed to determine the prevalence of neurological disorders and identify their risk factors in HIV-infected persons in Taiwan.MethodsWe identified 30,101 HIV-infected people between 2002 and 2016 from the National Health Insurance Research Database in Taiwan, and analyzed the incidence of neurological disorders. We applied a retrospective, nested case–control study design. The individuals with (case group) and without (control group) a neurological disorder were then matched by age, sex and time. Factors associated with neurological disorders were analyzed using a conditional logistic regression model, and a nomogram was generated to estimate the risk of developing a neurological disorder.ResultsThe incidence of neurological disorders was 13.67 per 1000 person-years. The incidence remained stable during the observation period despite the use of early treatment and more tolerable modern anti-retroviral therapy. The conditional logistic regression model identified nine clinical factors and comorbidities that were associated with neurological disorders, namely age, substance use, traumatic brain injury, psychiatric illness, HIV-associated opportunistic infections, frequency of emergency department visits, cART adherence, urbanization, and monthly income. These factors were used to establish the nomogram.ConclusionNeurological disorders are still prevalent in HIV-infected people in Taiwan. To efficiently identify those at risk, we established a nomogram with nine risk factors. This nomogram could prompt clinicians to initiate further evaluations and management of neurological disorders in this population.

An Updated Review on Electrochemical Nanobiosensors for Neurotransmitter Detection.

Neurotransmitters are chemical compounds released by nerve cells, including neurons, astrocytes, and oligodendrocytes, that play an essential role in the transmission of signals in living organisms, particularly in the central nervous system, and they also perform roles in realizing the function and maintaining the state of each organ in the body. The dysregulation of neurotransmitters can cause neurological disorders. This highlights the significance of precise neurotransmitter monitoring to allow early diagnosis and treatment. This review provides a complete multidisciplinary examination of electrochemical biosensors integrating nanomaterials and nanotechnologies in order to achieve the accurate detection and monitoring of neurotransmitters. We introduce extensively researched neurotransmitters and their respective functions in biological beings. Subsequently, electrochemical biosensors are classified based on methodologies employed for direct detection, encompassing the recently documented cell-based electrochemical monitoring systems. These methods involve the detection of neurotransmitters in neuronal cells in vitro, the identification of neurotransmitters emitted by stem cells, and the in vivo monitoring of neurotransmitters. The incorporation of nanomaterials and nanotechnologies into electrochemical biosensors has the potential to assist in the timely detection and management of neurological disorders. This study provides significant insights for researchers and clinicians regarding precise neurotransmitter monitoring and its implications regarding numerous biological applications.

Drug utilization evaluation of medications used in the management of neurological disorders

Background and objectThe burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition, with irrational drug use, which is also a global concern. Thus, drug utilization evaluation is designed to ensure appropriate medicine use within the healthcare settings. The aim of the study was to assess the rate and pattern of drug utilization in the management of neurological disorders. Materials and methodsA hospital-based cross-sectional drug utilization evaluation study on neurological drugs was carried out at the Department of Neurology over a span of six months. All legible prescriptions consisting neurological medications irrespective of patient's gender, aged ≥ 18 years were included for the study. The World Health Organization (WHO) core drug use indicators were used to assess the drug prescribing and utilization patterns. ResultsA total of 310 prescriptions were reviewed, where male predominance was found to be 56.45%. Out of 310 prescriptions, drugs belonging to 26 neurological classes were prescribed for the management of various neurological disorders. The majority of patients were diagnosed with epilepsy and the most prescribed drugs per patient were phenytoin (14.8%) and valproic acid (6.45%). By following the WHO core drug prescribing indicators, 65.47% of drugs prescribed from the India National List of Essential Medicines, 2022, followed by 29.83% of drugs prescribed in generic name and 10.86% of prescriptions including injections. ConclusionThe study findings showed that the prescribing pattern in the Department of Neurology was in accordance with the WHO core prescribing indicators. But, the extent of polypharmacy prescriptions was very high. Therefore, interventions are very necessary to promote rational drug prescribing patterns and thus clinical pharmacists can contribute to assess and review the drug utilization pattern to optimize the drug therapy and improvement in patient safety.

Quantitative-HPLC-DAD polyphenols analysis, anxiolytic and cognition enhancing potentials of Sorbaria tomentosa Lindl. Rehder

Ethnopharmacological relevanceMedicinal plants of the family Rosaceae have a long history of traditional uses in the management of neurological disorders. Sorbaria tomentosa Lindl. Rehder is composed of antioxidant and neuroprotective polyphenolics. Aims of the studyThe current study was designed to explore phenolics profile via high performance liquid chromatography-photodiode array detector (HPLC-DAD) and validated the neuroprotective and anxiolytic potentials of S. tomentosa by applying in vitro and in vivo approaches. Materials and methodsThe plant crude methanolic extract (St.Crm) and fractions were subjected to HPLC-DAD analysis for qualitative and quantitative assessment of phytochemicals. Samples were screened for in vitro free radicals scavenging assays by using 2,2-diphenylpicrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) along with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibition assays. For cognitive and anxiolytic studies, mice were subjected to open field, elevated plus maze (EPM), light-dark model, Y-maze, shallow water maze (SWM), and novel object recognition (NOR) tests. ResultsHPLC-DAD analysis revealed the presence of high concentrations of phenolic compounds. For instance, in St.Cr, 21 phenolics were quantified, among which apigenin-7-glucoside (291.6 mg/g), quercetin (122.1 mg/g), quercetin-3-feruloylsophoroside-7-glucoside (52.6 mg/g), quercetin-7-glucoside (51.8 mg/g), ellagic acid (42.7 mg/g), luteolin (45.0 mg/g), kaempferol (40.5 mg/g), 5-feruloylquinic acid (43.7 mg/g) were present in higher concentrations. Likewise, in ethyl acetate fraction (St.Et.Ac), 21 phenolics were identified as 3,5-di-caffeoylquinic acid (177.4 mg/g) and 5-hydroxybenzoylquinic acid (46.9 mg/g) were most abundant phytochemicals. Highly valuable phenolics were also identified in other fractions including butanol (St.Bt), chloroform (St.Chf), and n-hexane (St.Hex). The various fractions exhibited concentration dependent inhibition of free radicals in DPPH and ABTS assays. Potent AChE inhibitory potentials were revealed by the test samples with St.Chf, St.Bt and St.EtAc being the most active having an IC50 of 298.1, 580.1, and 606.47 μg mL−1, respectively. Similarly, St.Chf, St.Bt, St.EtAc and St.Cr exhibited potent BChE inhibitory activity and was observed as 59.14, 54.73, 51.35 and 49.44%, respectively. A significant improvement in the exploratory behavior was observed in open field test and stress/anxiety was relieved effectively at 50-100 mg/kg. Likewise, EPM, light-dark and NOR tests revealed an anxiolytic and memory enhancing behaviors. These effects were further corroborated from the Y-maze and SWM transgenic studies that showed considerable improvement in cognition retention. ConclusionsThese findings concluded that S. tomentosa possessed potential anxiolytic and nootropic efficacies and may have therapeutic potential in neurodegenerative disorders.

Decoding Artificial Intelligence in Neuroscience: Applications Beyond Diagnosis

Background: Artificial Intelligence has witnessed exponential expansion in health care applications. The article pronounces the dynamic excellence AI is achieving in the healthcare discipline of neuroscience. Objective: The paper highlights basic concepts of AI and acmes the interdisciplinary collaboration of Computational neuroscience, Cognitive science, and AI. Also, the article draws out important findings related to AI in neuroscience amongst its diverse application in the various disciplines. An ephemeral overview of applications of AI-based constructs in neurological disorders namely Neuroinflammation, Schizophrenia, Parkinson’s disease, Epilepsy, Autism spectrum disorder, Alzheimer’s disease, Brain tumor and Anesthesiology has been demonstrated in the present work. Methods: The method includes the collection of data from different search engines like google Scholar, PubMed, ScienceDirect, SciFinder, etc. to get coverage of relevant literature for accumulating appropriate information regarding AI, neuroscience, and their linkages. Results: These considerations are made to expand the existing literature on the progressing role of AI in the management of neurological disorders. Conclusion: The exponential expansion in the development of AI-based systems might aid in addressing the prevailing limitations in the domain of neurological disorders and neuroscience.

CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation

Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy. Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n=90) and epilepsy group (n=80), who were compared with three control groups including neurogenetic and structural (n=76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n=63), and headache (n=32). There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p<0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p=0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p≤0.0003), which was evident in most epilepsy subgroups. Here we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases. Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.

Exploring the Therapeutic Potential of the Ketogenic Diet on Neurological Disorders: A Comprehensive Review

The ketogenic diet (KD) has emerged as a promising therapeutic strategy for a variety of neurological disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. The potential benefits of the KD are attributed to its capacity to modulate neurotransmission, reduce inflammation, improve mitochondrial function, and enhance synaptic plasticity. Despite the growing body of evidence supporting the KD's therapeutic potential, there remain challenges in its implementation, such as potential side effects, nutrient deficiencies, and the need for careful monitoring by healthcare professionals. Factors affecting the success of the KD include patient adherence, individual metabolic response, and appropriate diet customization. This review summarizes the current evidence supporting the KD's role in the management of neurological disorders, discusses the underlying mechanisms of action, highlights the challenges and considerations associated with its use, and addresses the factors that can influence treatment success. Further research is needed to optimize the KD for different patient populations, elucidate the specific therapeutic mechanisms, and identify potential biomarkers to predict treatment response, ultimately enhancing the quality of life and overall well-being of individuals affected by neurological disorders.

The Interplay Between the Gut Microbiome and Neurological Disorders: Exploring the Gut-Brain Axis

The gut-brain axis is a complex communication system between the gut and the brain that has a significant impact on overall health and well-being. Recent evidence suggests that the gut microbiome plays a critical role in this communication system, and that imbalances in the gut microbiome can contribute to the development and progression of neurological disorders. In this comprehensive review, we provide an overview of the gut-brain axis, including the structure and function of the gut microbiome, and the various gut-brain communication pathways. We also discuss the role of dysbiosis, or imbalances in the gut microbiome, in the development and progression of neurological disorders, and the various gut-directed therapies that have been shown to be effective in these conditions, including probiotics, prebiotics, and fecal microbiota transplantation. Finally, we discuss the future directions and challenges in gut-brain research for neurological disorders, including the need for standardized and validated methods for measuring gut microbiome composition and function, and the complex and multi-factorial nature of the gut-brain axis. This review provides a comprehensive overview of the current state of the field and highlights the importance of the gut-brain axis in the management of neurological disorders.