Guía de tratamiento de la alteración aguda del estado mental. Academia Iberoamericana de Neurología Pediátrica / Guide for the treatment of acute altered mental status. Iberoamerican Academy of Pediatric Neurology

La alteración aguda del estado mental en pediatría se refiere a un cambio repentino y significativo en la función cerebral y el nivel de conciencia de un niño. Puede manifestarse como confusión, desorientación, agitación, letargo o incluso pérdida de la conciencia. Esta condición es una emergencia médica, y requiere una evaluación y una atención inmediatas. Existen diversas causas de alteración aguda del estado mental en niños, algunas de las cuales incluyen infecciones del sistema nervioso central, como la meningitis o la encefalitis, los traumatismos craneoencefálicos, los trastornos metabólicos, las convulsiones o las intoxicaciones, entre otras. Este estudio tuvo como objetivo analizar, preparar y calificar la bibliografía actual para determinar las mejores recomendaciones sobre el tratamiento ante casos de alteración aguda del estado mental en pediatría de diferentes causas. El estudio se basó en la calificación de expertos en el campo para poder determinar la calificación de las recomendaciones, además de ser sometido a la revisión por parte del comité científico de la Academia Iberoamericana de Neurología Pediátrica. Nuestra guía representa una ayuda para el tratamiento de este síntoma inespecífico desde un enfoque básico y avanzado, aplicable por cualquier neurólogo pediatra.(AU)

In pediatric patients, an acute altered mental status refers to a sudden and significant change in a child’s brain function and level of consciousness. It may manifest as confusion, disorientation, agitation, lethargy or even a loss of consciousness. This condition is a medical emergency, and requires immediate evaluation and attention. There are several causes of acute altered mental status in children, including infections of the central nervous system such as meningitis or encephalitis, traumatic brain injury, metabolic disorders, seizures and poisoning, among others. The aim of this study was to analyse, prepare and classify the current literature in order to determine the best recommendations for the treatment of cases of acute altered mental status with various causes in pediatric patients. The study was based on opinions from experts in the field in order to classify the recommendations, and was submitted to the scientific committee of the Iberoamerican Academy of Pediatric Neurology for review. Our guide is an aid for the treatment of this non-specific symptom based on a basic and advanced approach, which can be applied by any pediatric neurologist.(AU)

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice / Tratamiento concomitante de safinamida y antidepresivos: Datos de seguridad sobre la práctica en la vida real

Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. Results: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years ± 8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75 mg ± 233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. Conclusions: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.(AU)

Objetivos: El objetivo de este estudio ha sido evaluar las posibles interacciones farmacológicas entre safinamida y antidepresivos; en particular la aparición del síndrome serotoninérgico mediante datos obtenidos en la vida real. Material y métodos: Realizamos un estudio observacional retrospectivo de pacientes con enfermedad de Parkinson (EP) de nuestra unidad de trastornos del movimiento, que estaban en tratamiento con algún fármaco antidepresivo y safinamida. Específicamente, se examinaron los síntomas sugestivos de síndrome serotoninérgico. Además, se recogieron tiempos de uso simultáneo, dosis de levodopa y otros fármacos antiparkinsonianos concomitantes. Resultados: Se revisaron las historias clínicas correspondientes al período de estudio de septiembre de 2018 a septiembre de 2019. Setenta y ocho pacientes con EP se encontraban en tratamiento con safinamida, de los cuales 25 (32,05%) se encontraban recibiendo además un fármaco antidepresivo, siendo sertralina y escitalopram los más frecuentes. La edad media fue de 80 años ± 8,43 y el estadio H&Y fue de 3 [2-4]. La dosis media de levodopa utilizada fue de 703,75 mg ± 233,15. La mediana de duración del tratamiento concomitante con safinamida y un fármaco antidepresivo fue de 6 meses (IQR: 20,5), y más de 18 meses en 5 casos. No se registró ningún caso de síndrome serotoninérgico, ni tampoco ninguno de sus síntomas de forma aislada. Conclusión: Nuestro estudio de práctica clínica real sugiere que el uso concomitante de safinamida con fármacos antidepresivos en pacientes con EP parece ser seguro y bien tolerado, incluso a largo plazo. Sin embargo, es necesaria precaución, individualizando los regímenes de tratamiento, y controlando la posible aparición de efectos adversos.(AU)

Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review.

Preclinical and clinical studies have indicated that combining photobiomodulation (PBM) therapy with other therapeutic approaches may influence the treatment process in a variety of disorders. The purpose of this systematic review was to determine whether PBM-combined therapy provides additional benefits over monotherapies in neurologic and neuropsychiatric disorders. In addition, the review describes the most commonly used methods and PBM parameters in these conjunctional approaches.To accomplish this, a systematic search was conducted in Google Scholar, PubMed, and Scopus databases through January 2024. 95 potentially eligible articles on PBM-combined treatment strategies for neurological and neuropsychological disorders were identified, including 29 preclinical studies and 66 clinical trials.According to the findings, seven major categories of studies were identified based on disease type: neuropsychiatric diseases, neurodegenerative diseases, ischemia, nerve injury, pain, paresis, and neuropathy. These studies looked at the effects of laser therapy in combination with other therapies like pharmacotherapies, physical therapies, exercises, stem cells, and experimental materials on neurological disorders in both animal models and humans. The findings suggested that most combination therapies could produce synergistic effects, leading to better outcomes for treating neurologic and psychiatric disorders and relieving symptoms.These findings indicate that the combination of PBM may be a useful adjunct to conventional and experimental treatments for a variety of neurological and psychological disorders.

Exploring the mechanisms of kaempferol in neuroprotection: Implications for neurological disorders.

Kaempferol, a flavonoid compound found in various fruits, vegetables, and medicinal plants, has garnered increasing attention due to its potential neuroprotective effects in neurological diseases. This research examines the existing literature concerning the involvement of kaempferol in neurological diseases, including stroke, Parkinson's disease, Alzheimer's disease, neuroblastoma/glioblastoma, spinal cord injury, neuropathic pain, and epilepsy. Numerous in vitro and in vivo investigations have illustrated that kaempferol possesses antioxidant, anti-inflammatory, and antiapoptotic properties, contributing to its neuroprotective effects. Kaempferol has been shown to modulate key signaling pathways involved in neurodegeneration and neuroinflammation, such as the PI3K/Akt, MAPK/ERK, and NF-κB pathways. Moreover, kaempferol exhibits potential therapeutic benefits by enhancing neuronal survival, attenuating oxidative stress, enhancing mitochondrial calcium channel activity, reducing neuroinflammation, promoting neurogenesis, and improving cognitive function. The evidence suggests that kaempferol holds promise as a natural compound for the prevention and treatment of neurological diseases. Further research is warranted to elucidate the underlying mechanisms of action, optimize dosage regimens, and evaluate the safety and efficacy of this intervention in human clinical trials, thereby contributing to the advancement of scientific knowledge in this field.

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.

Ganoderic Acid A: A Potential Natural Neuroprotective Agent for Neurological Disorders: A Review.

Ganoderic acid A (GAA) is one of the major triterpenoids in Ganoderma lucidum (GL). Accumulating evidence has indicated that GAA demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Here, the effects and mechanisms of GAA in the treatment of neurological disorders were evaluated and discussed through previous research results. By summarizing previous research results, we found that GAA may play a neuroprotective role through various mechanisms: anti-inflammatory, anti-oxidative stress, anti-apoptosis, protection of nerve cells, and regulation of nerve growth factor. Therefore, GAA is a promising natural neuroprotective agent and this review would contribute to the future development of GAA as a novel clinical candidate drug for treating neurological diseases.

Efficacy of Hypnosis and Catalepsy Induction in Functional Neurological Disorders.

BACKGROUND: Patients with Functional Neurological Disorder (FND) experience complex patterns of motor and/or sensory symptoms. Treatment studies of psychological interventions are promising but limited. OBJECTIVES: The aim of the current pilot study is to investigate the effect of treatment consisting of a combination of hypnosis and catalepsy induction on FND symptom severity. METHODS: A within-subject waiting list-control design was used with 46 patients diagnosed with FND. The treatment consisted of 10 sessions. The primary outcome measure was FND symptom severity (The Psychogenic Movement Disorder Rating Scale; PMDRS). The secondary outcome measures were psychological distress and quality of life. RESULTS: The repeated measures (RM) ANOVA for the PMDRS as outcome measure revealed a significant effect for time with a large effect size (η2 = 0.679). Pairwise comparisons indicated that the effect of time in the treatment period was significant for the measure of FND symptom severity, whereas the waiting list period was not. The effect remained stable even at 8 weeks post treatment. As for the additional measurement, general psychological distress and quality of life, no statistically significant differences between individual time points were found. CONCLUSIONS: This pilot study showed that eight sessions of treatment consisting of a combination of hypnosis and catalepsy induction was effective in reducing FND symptom severity. Some explanations and limitations are provided in the paper as well as several avenues of future research.

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway.

As an important signaling pathway in multicellular eukaryotes, the Wnt signaling pathway participates in a variety of physiological processes. Recent studies have confirmed that the Wnt signaling pathway plays an important role in neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. The regulation of Wnt signaling by natural compounds in herbal medicines and nutraceuticals has emerged as a potential strategy for the development of new drugs for neurological disorders. Purpose: The aim of this review is to evaluate the latest research results on the efficacy of natural compounds derived from herbs and nutraceuticals in the prevention and treatment of neurological disorders by regulating the Wnt pathway in vivo and in vitro. A manual and electronic search was performed for English articles available from PubMed, Web of Science, and ScienceDirect from the January 2010 to February 2023. Keywords used for the search engines were "natural products,″ "plant derived products,″ "Wnt+ clinical trials,″ and "Wnt+,″ and/or paired with "natural products″/″plant derived products", and "neurological disorders." A total of 22 articles were enrolled in this review, and a variety of natural compounds from herbal medicine and nutritional foods have been shown to exert therapeutic effects on neurological disorders through the Wnt pathway, including curcumin, resveratrol, and querctrin, etc. These natural products possess antioxidant, anti-inflammatory, and angiogenic properties, confer neurovascular unit and blood-brain barrier integrity protection, and affect neural stem cell differentiation, synaptic formation, and neurogenesis, to play a therapeutic role in neurological disorders. In various in vivo and in vitro studies and clinical trials, these natural compounds have been shown to be safe and tolerable with few adverse effects. Natural compounds may serve a therapeutic role in neurological disorders by regulating the Wnt pathway. This summary of the research progress of natural compounds targeting the Wnt pathway may provide new insights for the treatment of neurological disorders and potential targets for the development of new drugs.

Functional neurologic disorder as a rare complication of dental local anaesthetics: two contrasting cases.

Adverse reactions to dental local anaesthetics are fortunately rare. However, when they occur, they can be severe and debilitating to the patient. Adverse reactions may be either prolonged anaesthesia, with or without dysaesthesia, or systemic reactions. Although these systemic reactions are commonly thought to be allergies, this is rarely the case. Much more commonly, these adverse systemic reactions are either cardiovascular or from the central nervous system. This paper describes two contrasting cases of functional neurologic disorder which illustrates the consequences and appropriate management. The responsibilities of the dentist who injected the local anaesthetic are outlined.

Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases.

Neurological disorders incidences are increasing drastically due to complex pathophysiology, and the nonavailability of disease-modifying agents. Several attempts have been made to identify new potential chemicals to combat these neurological abnormalities. At present, complete abolishment of neurological diseases is not attainable except for symptomatic relief. However, dietary recommendations to help brain development or improvement have increased over the years. In recent times, cruciferous vegetables and their phytochemicals have been identified from preclinical and clinical investigations as potential neuroprotective agents. The present review highlights the beneficial effects and molecular mechanisms of phytochemicals such as indole-3-carbinol, diindolylmethane, sulforaphane, kaempferol, selenium, lutein, zeaxanthin, and vitamins of cruciferous vegetables against neurological diseases including Parkinson's disease, Alzheimer's disease, stroke, Huntington's disease, autism spectra disorders, anxiety, depression, and pain. Most of these cruciferous phytochemicals protect the brain by eliciting antioxidant, anti-inflammatory, and antiapoptotic properties. Regular dietary intake of cruciferous vegetables may benefit the prevention and treatment of neurological diseases. The present review suggests that there is a lacuna in identifying the clinical efficacy of these phytochemicals. Therefore, high-quality future studies should firmly establish the efficacy of the above-mentioned cruciferous phytochemicals in clinical settings.

Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease.

BACKGROUND: With the development of modern medicine, the Traditional Chinese Medicine (TCM) combined with western medicine began to be produced and applied. Scalp acupuncture (SA) as a Chinese medicine based on neurological theory, has a great advantage compared with TCM in the treatment of nervous system diseases. METHOD: In this paper, we analyze the physiological and pathological manifestations of sexual dimorphism (SD) to illustrate the necessity of SD treatment. In addition, we review the factors that can affect SD and analyze in physiological structure, function, and pathological neurons. Diseases (pathological basis, pathological manifestations, and incidence) and factors leading to gender differences, which to analyze the possibility of gender differences in SA. RESULT: Furthermore, we creatively a new insight of SD-SA and provide the complete SD treatment cases on the basis of the existing SA in different kinds of diseases including stroke, migraine, attention deficit hyperactivity disorder (ADHD), and depression. CONCLUSION: In summary, we believe that it is feasible to improve the clinical effectiveness of SA, which is able to promote the development of SA, and then provides an actionable evidence for the promotion of precision medicine in the future.

Hypnosis and suggestion as interventions for functional neurological disorder: A systematic review.

OBJECTIVE: Functional neurological disorder (FND) involves the presence of neurological symptoms that cannot be explained by neurological disease. FND has long been linked to hypnosis and suggestion, both of which have been used as treatments. Given ongoing interest, this review examined evidence for the efficacy of hypnosis and suggestion as treatment interventions for FND. METHOD: A systematic search of bibliographic databases was conducted to identify group studies published over the last hundred years. No restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, extracted data, and rated study quality. RESULTS: The search identified 35 studies, including 5 randomised controlled trials, 2 non-randomised trials, and 28 pre-post studies. Of 1584 patients receiving either intervention, 1379 (87%) showed significant improvements, including many who demonstrated resolution of their symptoms in the short-term. Given the heterogeneity of interventions and limitations in study quality overall, more formal quantitative synthesis was not possible. CONCLUSIONS: The findings highlight longstanding and ongoing interest in using hypnosis and suggestion as interventions for FND. While the findings appear promising, limitations in the evidence base, reflecting limitations in FND research more broadly, prevent definitive recommendations. Further research seems warranted given these supportive findings.

New Insights into Prospective Health Potential of ω-3 PUFAs.

PURPOSE OF REVIEW: Docosahexaenoic acid and eicosapentaenoic acid are the two essential long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs) promoting human health which are obtained from diet or supplementation. The eicosanoids derived from ω-6 and ω-3 PUFAs have opposite characteristics of pro- and anti-inflammatory activities. The proinflammatory effects of ω-6 PUFAs are behind the pathology of the adverse health conditions of PUFA metabolism like cardiovascular diseases, neurological disorders, and inflammatory diseases. A balanced ω-6 to ω-3 ratio of 1-4:1 is critical to prevent the associated disorders. But due to modern agricultural practices, there is a disastrous shift in this ratio to 10-20:1. This review primarily aims to discuss the myriad health potentials of ω-3 PUFAs uncovered through recent research. It further manifests the importance of maintaining a balanced ω-6 to ω-3 PUFA ratio. RECENT FINDINGS: ω-3 PUFAs exhibit protective effects against diabetes mellitus-associated complications including diabetic retinopathy, diabetic nephropathy, and proteinuria. COVID-19 is also not an exception to the health benefits of ω-3 PUFAs. Supplementation of ω-3 PUFAs improved the respiratory and clinical symptoms in COVID-19 patients. ω-3 PUFAs exhibit a variety of health benefits including anti-inflammatory property and antimicrobial property and are effective in protecting against various health conditions like atherosclerosis, cardiovascular diseases, diabetes mellitus, COVID-19, and neurological disorders. In the present review, various health potentials of ω-3 PUFAs are extensively reviewed and summarized. Further, the importance of a balanced ω-6 to ω-3 PUFA ratio has been emphasized besides stating the diverse sources of ω-3 PUFA.

Environmental neurology: Concepts and short history of an interdisciplinary approach to etiology, treatment and prevention.

Environmental Neurology (EN), a sub-discipline of Neurology and Neurological Sciences, favors an interdisciplinary collaboration allowing a holistic approach to understanding the impact of environmental factors on the nervous system and their relationship with neurological diseases. Several examples of diseases and conditions show the large scope of subjects addressed by EN. The EN sub-discipline focuses on both individual and population issues thus joining patient care and public health, respectively. Neuropathogenesis is addressed by several major questions: How do the environment and nervous system interact? Which exogenous factors can trigger neurological disease? When, where and how do they act? What are the therapeutic implications, and how can these disorders be controlled or prevented. To answer such questions, we address the incentive for, philosophy of and methods developed by EN, which seeks to safeguard Brain Health and, thus, the quality of life.

Network pharmacology and molecular docking approaches predict the mechanisms of Corididius chinensis in treating manganese-induced nervous system diseases: A review.

Neurotoxicity could be induced by long exposure to manganese (Mn). The traditional Chinese medicine, Corididius chinensis (Cc) has been proven to have a certain curative effect on Mn poisoning. Therefore, network pharmacology was performed to explore potential therapeutic targets and pharmacological mechanisms of Cc. We found ingredients by building our own database through literature, (which is the first to screen traditional Chinese medicine without traditional Chinese medicine systems pharmacology database and analysis platform databases and it is applicable whenever a Chinese medicine is not found in the traditional Chinese medicine systems pharmacology database and analysis platform database) and potential targets of Mn-induced nervous system diseases from the OMIM, GeneCards, and DrugBank database were identified. A protein-protein interaction network was constructed using Cytoscape. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed for the treatment of Mn-induced nervous system disease, and molecular docking was carried out to verify the results of network pharmacology analysis. After screening disease-related genes, 12 intersecting genes overlapped between 284 target proteins of the active compound and 195 potential disease targets. The pathways of neurodegeneration_multiple diseases and Alzheimer disease pathway may be the most potential pathway of Cc treating Mn-induced nervous system diseases. CASP9 and PTGS2 in neurodegeneration_multiple diseases, NOS1, NOS2 in Alzheimer disease pathway were identified as core targets. Especially, molecule docking analysis unveil that aspongpyrazine A docking NOS2 is the most potential therapeutic drug and target, which primarily involved in the processes of oxidative stress and inflammation.

Effects of miglustat therapy on neurological disorder and survival in early-infantile Niemann-Pick disease type C: a national French retrospective study.

BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurodegeneration and premature death. While miglustat can stabilize neurological manifestations in later onset forms of NP-C, its efficacy in the early-infantile neurological form has not been demonstrated. In this observational retrospective study, we compared long-term neurodevelopmental outcome and survival between an untreated and a treated group of early infantile NP-C patients. METHODS: Data available on all NP-C patients with early infantile neurological onset diagnosed in France between 1990 and 2013 were compiled. Patients with incomplete data or who had died from a systemic perinatal, rapidly fatal form were excluded. RESULTS: Ten patients were included in the treated group (year of birth: 2006-2012), and 16 patients in the untreated group [born 1987-2005 (n = 15), 2012 (n = 1)]. The median age at neurological onset was 9 months (5-18) in the treated group, and 12 months (3-18) in the untreated group (p = 0.22). Miglustat therapy was started at a median age of 24.5 months (9-29) and median duration was 30 months (11-56). Gastrointestinal adverse events were reported in 7/10 patients on miglustat. All patients developed loss of psychomotor acquisitions or additional neurological symptoms despite miglustat therapy. The ages of developmental milestones and neurological involvement did not significantly differ between the two groups. Four patients in the untreated group were lost to follow up. The 22 remaining patients had died by the end of the study and no patient survived beyond the age of 7.4 years. The median survival age was 4.42 years in the untreated group and 5.56 years in the treated group; the Kaplan-Meier survival curves were not significantly different (log-rank test: p = 0.11). CONCLUSIONS: Miglustat allowed no significant long-term neurodevelopmental improvement nor significant increase of survival in patients with early infantile NP-C.

The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review.

Neurological diseases place a substantial burden on public health and have a serious impact on the quality of life of patients. Despite the multifaceted pathological process involved in the occurrence and development of these neurological diseases, each disease has its own unique pathological characteristics and underlying molecular mechanisms which trigger their onset. Thus, it is unlikely to achieve effective treatment of neurological diseases by means of a single approach. To this end, we reason that it is pivotal to seek an efficient strategy that implements multitherapeutic targeting and addresses the multifaceted pathological process to overcome the complex issues related to neural dysfunction. In recent years, natural medicinal plant-derived monomers have received extensive attention as new neuroprotective agents for treatment of neurological disorders. Fisetin, a flavonoid, has emerged as a novel potential molecule that enhances neural protection and reverses cognitive abnormalities. The neuroprotective effects of fisetin are attributed to its multifaceted biological activity and multiple therapeutic mechanisms associated with different neurological disorders. In this review article, we summarize recent research progression regarding the pharmacological effects of fisetin in treating several neurological diseases and the potential mechanisms.

An Overview of Chemistry, Kinetics, Toxicity and Therapeutic Potential of Boldine in Neurological Disorders.

Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties. There is a dearth of information regarding its pharmacokinetics and toxicity in addition to its potential pharmacological activity. Boldine belongs to the aporphine alkaloid class and possesses lipophilic properties which enable its efficient absorption and distribution throughout the body, including the central nervous system. It exhibits potent free radical scavenging activity, thereby reducing oxidative stress and preventing neuronal damage. Through a variety of neuroprotective mechanisms, including suppression of AChE and BuChE activity, blocking of connexin-43 hemichannels, pannexin 1 channel, reduction of NF-κß mediated interleukin release, and glutamate excitotoxicity which successfully reduces neuronal damage. These results point to its probable application in reducing neuroinflammation and oxidative stress in epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Moreover, its effects on serotonergic, dopaminergic, opioid, and cholinergic receptors were further investigated in order to determine its applicability for neurobehavioral dysfunctions. The article investigates the pharmacokinetics of boldine and reveals that it has a low oral bioavailability and a short half-life, requiring regular dosage to maintain therapeutic levels. The review studies boldine's potential therapeutic uses and mode of action while summarizing its neuroprotective benefits.  Given the favorable results for boldine as a potential neurotherapeutic drug in laboratory animals, more research is required. However, in order to optimise its therapeutic potential, it must be more bioavailable with fewer detrimental side effects.

Perturbations in Microbiota Composition as a Novel Mediator in Neuropsychiatric, Neurological and Mental Disorders: Preventive and Therapeutic Complementary Therapies to Balance the Change.

Although microbiology and neurology are separate disciplines, they are linked to some infectious and neurological diseases. Today, microbiome is considered as one of the biomarkers of health by many researchers. This has led to the association of microbiome changes with many neurological diseases. The natural microbiota has many beneficial properties. If disrupted and altered, it can lead to irreversible complications and many neurological diseases. Therefore, according to previous studies, some preventive and therapeutic complementary therapies can prevent or restore microbiome dysbiosis and inflammation in the nervous system. With our current perception of the microbiological basis for different neurological disorders, both aspects of drug treatment and control of perturbations of the microbiome should be considered, and targeting them simultaneously will likely help to attain favorable results.