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Neurochemical dysregulations resulting from N-methyl-D-aspartate hypofunction (NMDA), are exacerbated by neuroimmune and oxidative stress and are known risk factors for neuropsychiatric disorders like schizophrenia-like diseases. Here, we investigate the protective and curative effects, and mechanisms of silymarin, a polyphenolic flavonoid with neuroprotective functions in preventive-reversal model of ketamine, an NMDA antagonist in mice. Mice were grouped into 6 cohorts (n = 9). In the pre-treatment, groups 1 and 2 received saline (10 mL/kg/p.o.), groups 3 and 4 (silymarin, 50 and 100 mg/kg/p.o.), and group 5 (risperidone, 0.5 mg/kg/p.o.) consecutively for 14 days, then combined with ketamine (20 mg/kg/i.p.) injection in groups 2–5 from days 8–14. However, mice in reversal study received intraperitoneal injection of ketamine for 14 days before silymarin (50 and 100 mg/kg, p.o) and risperidone (0.5 mg/kg, p.o.) treatment between days 8–14. The consequences on schizophrenia-like behavior, neurochemistry, inflammation, and oxidative/nitrergic stress markers were evaluated in critical brain regions of the disease. Silymarin prevented and reversed ketamine-induced increase in dopamine, 5-hydroxyltryptamine, acetylcholinesterase, malondialdehyde and nitrite levels in the striatum, prefrontal-cortex and hippocampus. These were accompanied by improvement in hyperlocomotion, stereotypy, memory, and social impairments, notably devoid of cataleptogenic potential. Complementarily, silymarin reduced myeloperoxidase, tumor-necrosis factor-α, and interleukin-6 concentrations relative to the ketamine group. Moreover, ketamine-induced decreased brain-derived neurotrophic factor, glutathione, catalase, superoxide-dismutase levels were normalized by silymarin in the brain regions relative to ketamine. Overall, these findings suggest that silymarin's antipsychotic effect might be primarily associated, among other mechanisms, with the normalization of neurochemical and neurotrophic changes in the mice brains. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders involve progressive dysfunction and loss of synapses and neurons and brain atrophy, slowly declining memories and cognitive skills, throughout a long process. Alzheimer's disease (AD), the leading neurodegenerative disorder, suffers from a lack of effective therapeutic drugs. Decades of efforts targeting its pathologic hallmarks, amyloid plaques and neurofibrillary tangles, in clinical trials have produced therapeutics with marginal benefits that lack meaningful clinical improvements in cognition. Delivering meaningful clinical therapeutics to treat or prevent neurodegenerative disorders thus remains a great challenge to scientists and clinicians. Emerging evidence, however, suggests that dysfunction of various synaptogenic signaling pathways participates in the neurodegenerative progression, resulting in deterioration of operation/structure of the synaptic networks involved in cognition. These derailed endogenous signaling pathways and disease processes are potential pharmacological targets for the therapies. Therapeutics with meaningful clinical benefit in cognition may depend on the effectiveness of arresting and reversing the neurodegenerative process through these targets. In essence, promoting neuro-regeneration may represent the only option to recover degenerated synapses and neurons. These potential directions in clinical trials for AD therapeutics with meaningful clinical benefit in cognitive function are summarized and discussed. [ABSTRACT FROM AUTHOR]

Introduction: Sleep disorders are common in the general population, necessitating the search for new strategies to address this public health challenge. The study aims to describe the electrocorticographic and behavioral changes in sleep deprived Wistar rats exposed to varying doses of camphor, to assess its effects on sleep and its potential as a sleep-inducing drug. Materials and Methods: For the electrocorticographic evaluation, seventy-two rats were randomly assigned to distinct groups: a control group, a sleep-deprived group, three sleep-deprived groups receiving 10, 20, and 30 mg/kg i.p. of camphor respectively, and three groups that received these doses without sleep deprivation. For the behavioral analysis, twenty-seven rats were divided into three groups, each receiving the same doses as the previous test. Results and Discussion: Our results showed that there was a decrease in the frequency of brain oscillatory patterns when camphor was administered at 10 mg/kg i.p. whereas there was a dose-dependent increase in the spectral power and distribution following the administration of 20 and 30 mg/kg i.p., with the emergence of Delta, Theta, Alpha, and Beta waves. As for the behavioral analysis, it was demonstrated that testicular relaxation, decreased motility, and light sleep induction also occurred in a dose-dependent manner. Thus, we conclude that camphor administration intensifies occipital electrocorticographic patterns in sleep-deprived rats, and its electrocorticographic and behavioral analysis could indicate a potential as a supporting agent in the insomnia treatment. [ABSTRACT FROM AUTHOR]

α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (AMPARs) mediate rapid excitatory synaptic transmission in the mammalian brain, primarily driven by the neurotransmitter glutamate. The modulation of AMPAR activity, particularly calcium‐permeable AMPARs (CP‐AMPARs), is crucially influenced by various auxiliary subunits. These subunits are integral membrane proteins that bind to the receptor's core and modify its functional properties, including ion channel kinetics and receptor trafficking. This review comprehensively catalogs all known AMPAR auxiliary proteins, providing vital insights into the biochemical mechanisms governing synaptic modulation and the specific impact of CP‐AMPARs compared to their calcium‐impermeable AMPA receptor (CI‐AMPARs). Understanding the complex interplay between AMPARs and their auxiliary subunits in different brain regions is essential for elucidating their roles in cognitive functions such as learning and memory. Importantly, alterations in these auxiliary proteins' expression, function or interactions have been implicated in various neurological disorders. Aberrant signaling through CP‐AMPARs, in particular, is associated with severe synaptic dysfunctions across neurodevelopmental, neurodegenerative and psychiatric conditions. Targeting the distinct properties of AMPAR‐auxiliary subunit complexes, especially those involving CP‐AMPARs, could disclose new therapeutic strategies, potentially allowing for more precise interventions in treating complex neuronal disorders. [ABSTRACT FROM AUTHOR]

Behavioral neuropharmacology, a branch of neuroscience, uses behavioral analysis to demonstrate treatment effects on animal models, which is fundamental for pre-clinical evaluation. Typically, this determination is univariate, neglecting the relevant associations for understanding treatment effects in animals and humans. This study implements regression trees and Bayesian networks from a multivariate perspective by using variables obtained from behavioral tests to predict the time spent in the open arms of the elevated arm maze, a key variable to assess anxiety. Three doses of allopregnanolone were analyzed and compared to a vehicle group and a diazepam-positive control. Regression trees identified cut-off points between the anxiolytic and anxiogenic effects, with the anxiety index standing out as a robust predictor, combined with the percentage of open-arm entries and the number of entries. Bayesian networks facilitated the visualization and understanding of the interactions between multiple behavioral and biological variables, demonstrating that treatment with allopregnanolone (2 mg) emulates the effects of diazepam, validating the multivariate approach. The results highlight the relevance of integrating advanced methods, such as Bayesian networks, into preclinical research to enrich the interpretation of complex behavioral data in animal models, which can hardly be observed with univariate statistics. [ABSTRACT FROM AUTHOR]

In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILEs). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic (AE) drugs, have become increasingly evident. Data spanning a 10-year period (2010–2020) were analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. This study focused on reviewing relevant case reports detailing successful intravenous lipid emulsion (ILE) administration in patients with acute intoxications with antiepileptics, specifically examining the impact of fat emulsions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval concerning hemodynamic instability. The typical symptoms of antiepileptic toxicity include central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion application resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults. This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches. The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects [ABSTRACT FROM AUTHOR]

The aim of the article is to briefly describe our work together with Dr. Viktor Mutt. He discovered and purified many new gastrointestinal bioactive neuropeptides that have important applications as therapeutic agents in diabetes, epilepsy, migraine and weight control. Dr. Muttâs strategy was to search for C­-terminally amidated peptides. We determined neuropeptide Y equilibrium binding for its receptor. Our work also included the L­-Ala scan of pharmacophores of the neuropeptide galanin (1­28). Finally, the work led to the establishment of the coexistence of peptides with small molecule neurotransmitters, such as serotonin, acetylcholine, noradrenaline and dopamine in central and peripheral neurons.

Electrophysiological methods of research are widely used in neurobiology. To assess the bioelectrical activity of the brain in small laboratory animals, electrocorticography (ECoG) is most often used, which allows the recording of signals directly from the cerebral cortex. To date, a number of methodological approaches to the manufacture and implantation of ECoG electrodes have been proposed, the complexity of which is determined by experimental tasks and logistical capabilities. Existing methods for analyzing bioelectrical signals are used to assess the functional state of the nervous system in test animals, as well as to identify correlates of pathological changes or pharmacological effects. The review presents current areas of applications of ECoG in neuropharmacological studies in small laboratory animals. Traditionally, this method is actively used to study the antiepileptic activity of new molecules. However, the possibility of using ECoG to assess the neuroprotective activity of drugs in models of traumatic, vascular, metabolic, or neurodegenerative CNS damage remains clearly underestimated. Despite the fact that ECoG has a number of disadvantages and methodological difficulties, the recorded data can be a useful addition to traditional molecular and behavioral research methods. An analysis of the works in recent years indicates a growing interest in the method as a tool for assessing the pharmacological activity of psychoactive drugs, especially in combination with classification and prediction algorithms. [ABSTRACT FROM AUTHOR]

The nicotinic acetylcholine receptor has served, since its biochemical identification in the 1970s, as a model of an allosteric ligand-gated ion channel mediating signal transition at the synapse. In recent years, the application of X-ray crystallography and high-resolution cryo–electron microscopy, together with molecular dynamic simulations of nicotinic receptors and homologs, have opened a new era in the understanding of channel gating by the neurotransmitter. They reveal, at atomic resolution, the diversity and flexibility of the multiple ligand-binding sites, including recently discovered allosteric modulatory sites distinct from the neurotransmitter orthosteric site, and the conformational dynamics of the activation process as a molecular switch linking these multiple sites. The model emerging from these studies paves the way for a new pharmacology based, first, upon the occurrence of an original mode of indirect allosteric modulation, distinct from a steric competition for a single and rigid binding site, and second, the design of drugs that specifically interact with privileged conformations of the receptor such as agonists, antagonists, and desensitizers. Research on nicotinic receptors is still at the forefront of understanding the mode of action of drugs on the nervous system. [ABSTRACT FROM AUTHOR]

One element, potassium, can be identified as the connecting link in the research of Czech neurophysiologist Prof. František Vyskočil. It accompanied him from the first student experiments on the frog muscle (Solandt effect) via sodium-potassium pump and quantum and non-quantum release of neurotransmitters (e.g. acetylcholine) to the most appreciated work on the reversible leakage of K+ from brain neurons during the Leao´s spreading cortical depression, often preceding migraine. He used a wide range of methods at the systemic, cellular and genetic levels. The electrophysiology and biochemistry of nerve-muscle contacts and synapses in the muscles and brain led to a range of interesting findings and discoveries on normal, denervated and hibernating laboratory mammals and in tissue cultures. Among others, he co-discovered the facilitating effects of catecholamines (adrenaline in particular) by end-plate synchronization of individual evoked quanta. This helps to understand the general effectiveness of nerve-muscle performance during actual stress. After the transition of the Czech Republic to capitalism, together with Dr. Josef Zicha from our Institute, he was an avid promoter of scientometry as an objective system of estimating a scientist´s success in basic research (journal Vesmír, 69: 644-645, 1990 in Czech). [ABSTRACT FROM AUTHOR]

The exploration of heterocyclic compounds and their fused analogs, featuring key pharmacophore fragments like pyridine, thiophene, pyrimidine, and triazine rings, is pivotal in medicinal chemistry. These compounds possess a wide array of biological activities, making them an intriguing area of study. The quest for new neurotropic drugs among derivatives of these heterocycles with pharmacophore groups remains a significant research challenge. The aim of this research work was to develop a synthesis method for new heterocyclic compounds, evaluate their neurotropic and neuroprotective activities, study histological changes, and perform docking analysis. Classical organic synthesis methods were used in the creation of novel heterocyclic systems containing pharmacophore rings. To evaluate the neurotropic activity of these synthesized compounds, a range of biological assays were employed. Docking analysis was conducted using various software packages and methodologies. The neuroprotective activity of compound 13 was tested in seizures with and without pentylenetetrazole (PTZ) administration. Histopathological examinations were performed in different experimental groups in the hippocampus and the entorhinal cortex. As a result of chemical reactions, 16 new, tetra- and pentacyclic heterocyclic compounds were obtained. The biologically studied compounds exhibited protection against PTZ seizures as well as some psychotropic effects. The biological assays evidenced that 13 of the 16 studied compounds showed a high anticonvulsant activity by antagonism with PTZ. The toxicity of the compounds was low. According to the results of the study of psychotropic activity, it was found that the selected compounds have a sedative effect, except compound 13, which exhibited activating behavior and antianxiety effects (especially compound 13). The studied compounds exhibited antidepressant effects, especially compound 13, which is similar to diazepam. Histopathological examination showed that compound 13 produced moderate changes in the brain and exhibited neuroprotective effects in the entorhinal cortex against PTZ-induced damage, reducing gliosis and neuronal loss. Docking studies revealed that out of 16 compounds, 3 compounds bound to the γ-aminobutyric acid type A (GABAA) receptor. Thus, the selected compounds demonstrated anticonvulsant, sedative, and activating behavior, and at the same time exhibited antianxiety and antidepressant effects. Compound 13 bound to the GABAA receptor and exhibited antianxiety, antidepressant, and neuroprotective effects in the entorhinal cortex against PTZ-induced changes. [ABSTRACT FROM AUTHOR]

The aim of the article is to briefly describe our work together with Dr. Viktor Mutt. He discovered and purified many new gastrointestinal bioactive neuropeptides that have important applications as therapeutic agents in diabetes, epilepsy, migraine and weight control. Dr. Mutt's strategy was to search for Cterminally amidated peptides. We determined neuropeptide Y equilibrium binding for its receptor. Our work also included the LAla scan of pharmacophores of the neuropeptide galanin (128). Finally, the work led to the establishment of the coexistence of pep tides with small molecule neurotransmitters, such as serotonin, acetylcholine, noradrenaline and dopamine in central and peripheral neurons. [ABSTRACT FROM AUTHOR]

Aloe barbadensis, Capparis spinosa, and Senegalia senegal are popular in traditional medicine due to their therapeutic effects. We aimed to assess the neuropharmacological potential of their extracts, including the impact on pain-relief, anxiety, depression, muscle relaxation, and motor coordination. BALB/c mice were administered with standardized doses of A. barbadensis, C. spinosa, and S. senegal extracts, and their behavior was recorded through various neurobehavioral tests. The antioxidant potential of the extracts was also evaluated by DPPH assay. A differential response was observed among the three extracts for analgesic activity. A. barbadensis showed an increase in latency time after an increase in dose, while C. spinosa and S. senegal exhibited a biphasic response. A. barbadensis showed very good anxiolytic effects and best anti-depression effects. S. senegal exhibited the best antioxidant activity, followed by A. barbadensis and C. spinosa. This shows that these plants could counteract oxidative stress and protect neurons from potential damage caused by free radicals. The observed anxiolytic, muscle relaxant effects, and enhanced antioxidant potential of the selected plants in BALB/c mice, indicate their potential therapeutic value in neuroprotective strategies and the treatment of oxidative stress-related neurological disorders. However, further investigations into their underlying mechanisms and long-term safety profiles are suggested before considering their translation into clinical applications. [ABSTRACT FROM AUTHOR]

Soybean is scientifically known as Glycine max. It belongs to the Fabaceae family. It consists of a lot of bioactive phytochemicals like saponin, phenolic acid, flavonoid, sphingolipids and phytosterols. It also owns excellent immune‐active effects in the physiological system. Soy and its phytochemicals have been found to have pharmacological properties that include anticancer, antioxidant, anti‐hypercholesterolaemic, anti‐diabetic, oestrogenic, anti‐hyperlipidaemic, anti‐inflammatory, anti‐obesity, anti‐hypertensive, anti‐mutagenic, immunomodulatory, anti‐osteoporotic, antiviral, hepatoprotective, antimicrobial, goitrogenic anti‐skin ageing, wound healing, neuroprotective and anti‐photoageing activities. Present study has been designed to set standard pharmacognostical extraction method, complexation of compounds, qualitative evaluation through phytochemical screening, identification by TLC, physicochemical properties, solubility profile, total phenolic, flavonoid content as well as analytical evaluation or characterisation like UV and FT‐IR of methanolic extract of G. max. The final observations like physicochemical properties such as total ash value, LOD and pH were recorded. Phytochemical screenings show the presence of flavonoid, alkaloid, saponin, carbohydrate, tannins, protein, gums and mucilage, fixed oils and fats. The results were found significant. Further in silico studies proved creatinine and euparin to be potent wound healing agents. [ABSTRACT FROM AUTHOR]

Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom's benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product. [ABSTRACT FROM AUTHOR]

Neuropharmacology is a multidisciplinary field in which neuro sciences and pharmacology professions cross, supposing the function of drugs in the brainand behaviour. This essay addresses various aspects covering neuropharmacology including the neurotransmission principles, drug development rationale, pharmacological principles, and therapeutic targets. The discussion occurs with a neurotransmission exploration first, and it puts the neurotransmitter receptors for mobilisation and their significance to neuronal communication and brain functioning. In the next section, a discussion regarding the interaction between drugs and neurotransmitter systems and the mechanism of action of various discrete classes of neuropharmacological agents is carried out. The article does not ignore the pharmacology and neuropharmacology methods, which include invitro assays, animal models, and imaging techniques, which are indispensable to exploring the effects of drugs on the nervous system. In addition, the processes of drug discovery and development in neuropharmacology are discussed. The article revea ls what difficulties the authors are facing and what was achieved recently. [ABSTRACT FROM AUTHOR]

Neohesperidin (hesperetin 7-O-neohesperidoside), a well-known flavanone glycoside widely found in citrus fruits, exhibits a variety of biological activities, with potential applications ranging from food ingredients to therapeutics. The purpose of this manuscript is to provide a comprehensive overview of the chemical, biosynthesis, and pharmacokinetics profiles of neohesperidin, as well as the therapeutic effects and mechanisms of neohesperidin against potential diseases. This literature review covers a wide range of pharmacological responses elicited by Neohesperidin, including neuroprotective, anti-inflammatory, antidiabetic, antimicrobial, and anticancer activities, with a focus on the mechanisms of those pharmacological responses. Additionally, the mechanistic pathways underlying the compound's osteoporosis, antiulcer, cardioprotective, and hepatoprotective effects have been outlined. This review includes detailed illustrations of the biosynthesis, biopharmacokinetics, toxicology, and controlled release of neohesperidine. Neohesperidin demonstrated a broad range of therapeutic and biological activities in the treatment of a variety of complex disorders, including neurodegenerative, hepato-cardiac, cancer, diabetes, obesity, infectious, allergic, and inflammatory diseases. Neohesperidin is a promising therapeutic candidate for the management of various etiologically complex diseases. However, further in vivo and in vitro studies on mechanistic potential are required before clinical trials to confirm the safety, bioavailability, and toxicity profiles of neohesperidin. [ABSTRACT FROM AUTHOR]

Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress‐related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre‐clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1–10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water‐loaded. The KOP antagonist norbinaltorphimine (norBNI, 10 mg/kg) was administered 24 h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses ≥ 3 mg/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre‐administration. Water‐loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females. [ABSTRACT FROM AUTHOR]

IntroductionSleep disorders are common in the general population, necessitating the search for new strategies to address this public health challenge. The study aims to describe the electrocorticographic and behavioral changes in sleep deprived Wistar rats exposed to varying doses of camphor, to assess its effects on sleep and its potential as a sleep-inducing drug.Materials and MethodsFor the electrocorticographic evaluation, seventy-two rats were randomly assigned to distinct groups: a control group, a sleep-deprived group, three sleep-deprived groups receiving 10, 20, and 30 mg/kg i.p. of camphor respectively, and three groups that received these doses without sleep deprivation. For the behavioral analysis, twenty-seven rats were divided into three groups, each receiving the same doses as the previous test.Results and DiscussionOur results showed that there was a decrease in the frequency of brain oscillatory patterns when camphor was administered at 10 mg/kg i.p. whereas there was a dose-dependent increase in the spectral power and distribution following the administration of 20 and 30 mg/kg i.p., with the emergence of Delta, Theta, Alpha, and Beta waves. As for the behavioral analysis, it was demonstrated that testicular relaxation, decreased motility, and light sleep induction also occurred in a dose-dependent manner. Thus, we conclude that camphor administration intensifies occipital electrocorticographic patterns in sleep-deprived rats, and its electrocorticographic and behavioral analysis could indicate a potential as a supporting agent in the insomnia treatment.

The article "Acute Thrombocytopenia Likely Induced by Apomorphine: A Case Report" discusses a case of a 79-year-old patient with Parkinson's disease who developed thrombocytopenia likely induced by apomorphine treatment. The patient experienced severe thrombocytopenia, which improved after discontinuation of apomorphine and administration of corticosteroids. The article highlights the rarity of thrombocytopenia induced by apomorphine and discusses the pathophysiology and management of drug-induced thrombocytopenia. The patient's recovery was successful, with platelet count returning to normal levels after treatment. [Extracted from the article]

Abstract Background Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well‐being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. Methods We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. Results Fifty‐eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. Conclusions Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

Glioblastoma multiforme (GBM) is one of the most common and lethal forms of brain cancer, carrying a very poor prognosis (median survival of -15 months post-diagnosis). Treatment typically involves invasive surgical resection of the tumour mass, followed by radiotherapy and adjuvant chemotherapy using the alkylating agent temozolomide, but over half of patients do not respond to this drug and considerable resistance is observed. Tumour heterogeneity is the main cause of therapeutic failure, where diverse progenitor glioblastoma stem cell (GSC) lineages in the microenvironment drive tumour recurrence and therapeutic resistance. The apelin receptor is a class A GPCR that binds two endogenous peptide ligands, apelin and ELA, and plays a role in the proliferation and survival of cancer cells. Here, we used quantitative whole slide immunofluorescent imaging of human GBM samples to characterise expression of the apelin receptor and both its ligands in the distinct GSC lineages, namely neural-progenitor-like cells (NPCs), oligodendrocyte-progenitor-like cells (OPCs), and mesenchymal-like cells (MES), as well as reactive astrocytic cells. The data confirm the presence of the apelin receptor as a tractable drug target that is common across the key cell populations driving tumour growth and maintenance, offering a potential novel therapeutic approach for patients with GBM. [ABSTRACT FROM AUTHOR]

Summary: Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg−1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF‐04859989 (30 mg kg−1; s.c.); or (iv) PF‐04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non‐rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non‐rapid eye movement sleep delta power and sleep spindles. PF‐04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non‐rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics. [ABSTRACT FROM AUTHOR]

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The present research aims to explore the intricate link between SARS-CoV infection and susceptibility to Alzheimer's disease, focusing on the role of APOE4, a genetic factor associated with both conditions. Our research aims to uncover shared molecular pathways, considering APOE4's impact on lipid metabolism, immune responses, and neuroinflammation relevant to COVID-19 and AD. The Chyawanprash phytocompounds were subjected to in-silico ADMET profiling and Zeatin a neuroprotective cytokinin emerged as a promising regulator of the ACE2-SPIKE complex as it exhibits favourable pharmacological attributes, presenting as a non-substrate for Permeability glycoprotein, low Protein Binding Percentage, and distinctive toxicity endpoints. Therapeutic candidate. Zeatin's robust binding disrupts the intricate APOE4-ACE2-SPIKE interplay (AAS), offering a potential therapeutic avenue that is further corroborated by Molecular dynamic simulation as the system remained stable without any major fluctuation throughout the 100ns simulation. The AAS binding free energy, determined as -124.849 +/- 15.513 KJ/mol using MMPBSA assay, reveals significant contributions to complex stability from amino acids including, GLN41: 1.211 kcal/mol, GLU340: 1.188 kcal/mol, ALA344: 1.198 kcal/mol, while ARG38: 2.011 kcal/mol establishes pivotal strong bonds integral to the interaction between AAS and Zeatin. Rigorous cytotoxicity assessments reveal Zeatin's safety profile, highlighting its inhibitory effect on LN18 cell viability that sharply decreases to 32.47% at 200 µg/ml, underscoring its modulatory impact on cellular metabolism. These findings enhance our understanding of the convergent mechanisms linking SARS-CoV and AD, providing valuable insights for potential therapeutic interventions. Further research is warranted to elucidate the specific pathways and molecular mechanisms through which zeatin exerts its protective effects. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well‐being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. Methods: We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. Results: Fifty‐eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. Conclusions: Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research. [ABSTRACT FROM AUTHOR]

No clinically effective therapeutics for Alzheimer's disease (AD) are currently available. Recently approved monoclonal antibodies for AD are rather limited in improving cognitive functions in AD, as well as having significant safety issues. The balance between neurodegeneration and neuroregeneration in the brain is dynamic, depending on brain injury and activity and regulation of several neuronal signal pathways. Recent clinical trials demonstrated the emerging concept that shifting/switching neuronal/synaptic degeneration to regeneration is achievable, can rescue cognitive functions, and prevent dementia progression in patients with AD. The pharmacological shift from neurodegeneration to neuroregeneration represents a novel effective cognition therapeutic in patients with AD and a preventive compound in individuals with preclinical AD by building up cognitive resilience. Alzheimer's disease (AD), similar to AD-related dementias, is characterized by impaired/lost neuronal structures and functions due to a long progression of neurodegeneration. Derailed endogenous signal pathways and disease processes have critical roles in neurodegeneration and are pharmacological targets in inducing neuroregeneration. Pharmacologically switching/shifting the brain status from neurodegeneration to neuroregeneration is emerging as a new therapeutic concept, one that is not only achievable, but also essential for effective therapy for AD. The results of the pharmacological-induced shift from neurodegeneration to neuroregeneration are twofold: arresting cognitive deterioration (and directing the brain toward cognitive recovery) in established AD, and preventing neurodegeneration through building up cognitive resilience in patients with preclinical or probable AD. In this review, we discuss these new developments in AD pharmacology and relevant clinical trials. [ABSTRACT FROM AUTHOR]

Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders. [ABSTRACT FROM AUTHOR]

Background: Neurotransmitter deficits and spatial associations among neurotransmitter distribution, brain activity, and clinical features in Parkinson's disease (PD) remain unclear. Better understanding of neurotransmitter impairments in PD may provide potential therapeutic targets. Therefore, we aimed to investigate the spatial relationship between PD-related patterns and neurotransmitter deficits. Methods: We included 59 patients with PD and 41 age- and sex-matched healthy controls (HCs). The voxel-wise mean amplitude of the low-frequency fluctuation (mALFF) was calculated and compared between the two groups. The JuSpace toolbox was used to test whether spatial patterns of mALFF alterations in patients with PD were associated with specific neurotransmitter receptor/transporter densities. Results: Compared to HCs, patients with PD showed reduced mALFF in the sensorimotor- and visual-related regions. In addition, mALFF alteration patterns were significantly associated with the spatial distribution of the serotonergic, dopaminergic, noradrenergic, glutamatergic, cannabinoid, and acetylcholinergic neurotransmitter systems (p

The serotonin-gated ion channel (5-HT3R) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive antagonists widely used as antiemetics, and is involved in several neurological diseases. Cryo-electron microscopy (cryo-EM) of the 5-HT3R in complex with serotonin or setrons revealed that the protein has access to a wide conformational landscape. However, assigning known high-resolution structures to actual states contributing to the physiological response remains a challenge. In the present study, we used voltage-clamp fluorometry (VCF) to measure simultaneously, for 5-HT3R expressed at a cell membrane, conformational changes by fluorescence and channel opening by electrophysiology. Four positions identified by mutational screening report motions around and outside the serotonin-binding site through incorporation of cysteine-tethered rhodamine dyes with or without a nearby quenching tryptophan. VCF recordings show that the 5-HT3R has access to four families of conformations endowed with distinct fluorescence signatures: ‘resting-like’ without ligand, ‘inhibited-like’ with setrons, ‘pre-active-like’ with partial agonists, and ‘active-like’ (open channel) with partial and strong agonists. Data are remarkably consistent with cryo-EM structures, the fluorescence partners matching respectively apo, setron-bound, 5-HT bound-closed, and 5-HT-bound-open conformations. Data show that strong agonists promote a concerted motion of all fluorescently labeled sensors during activation, while partial agonists, especially when loss-of-function mutations are engineered, stabilize both active and pre-active conformations. In conclusion, VCF, though the monitoring of electrophysiologically silent conformational changes, illuminates allosteric mechanisms contributing to signal transduction and their differential regulation by important classes of physiological and clinical effectors.

The circadian rhythm is a critical system that governs an organism’s functions in alignment with the light-dark cycle. Melatonin release from the pineal gland plays a crucial role in regulating the internal clock of the body. Multiple neurotransmitter systems in the central nervous system are linked to the release of melatonin. In this review, the relationship between circadian rhythm, melatonin secretion and various neurotransmitter systems are mainly discussed. Serotonin regulates the circadian rhythm through projections from raphe nuclei. Agomelatine is an example of the synergistic interaction between melatonin and serotonin. Melatonergic agents and selective serotonin reuptake inhibitors also exert notable impacts on depression in concomitant use. Dopamine has an inhibitory effect on melatonin release, while melatonin also inhibits dopamine release. This should be taken into account when considering the use of melatonin in Parkinson’s disease. On the contrary, use of melatonin may offer therapeutic advantages for schizophrenia and tardive dyskinesia. The interaction between norepinephrine and melatonin exhibits diurnal variability, with norepinephrine promoting arousal and inhibiting daytime melatonin secretion. Melatonergic neurons also exert a specific protective influence on cholinergic neurons. Interaction between the histaminergic and melatonergic systems is significant, particularly in association with immunity, sleep, and circadian rhythm. Novel ligands with dual-acting properties, interacting with both the histaminergic and melatonergic systems are investigated. Currently, there is a limited number of approved melatonergic agents that primarily demonstrate positive effects in addressing insomnia and depression. However, there is considerable potential in studying new agents that target both the melatonergic and other neurotransmitter systems, which alleviate various conditions, including neurodegenerative diseases, dementia, autoimmune diseases, allergic diseases, epilepsy, and other neuropsychiatric disorders. The ongoing process of developing and evaluating new ligands selectively targeting the melatonergic system remains crucial in understanding the complex relationship between these systems.

A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life and functionality. They cause two types of damage to the brain: primary and secondary. Secondary damage is particularly critical as it involves complex processes unfolding after the initial injury. These processes can lead to cell damage and death in the brain. Understanding how these processes damage the brain is crucial for finding new treatments. This review examines a wide range of literature from 2021 to 2023, focusing on biomarkers and molecular mechanisms in TBIs to pinpoint therapeutic advancements. Baseline levels of biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) in TBI, have demonstrated prognostic value for cognitive outcomes, laying the groundwork for personalized treatment strategies. In terms of pharmacological progress, the most promising approaches currently target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce a TBI's impact and aid in neurological rehabilitation. Future research is poised to refine these therapeutic approaches, potentially revolutionizing TBI treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Standard phytochemical investigations were performed to identify the secondary metabolites in the methanol extract of Chaetocarpus castanocarpus bark (MECC) and investigate the neuropharmacological potential of MECC in Swiss albino mice. MATERIALS AND METHODS: Swiss albino mice were used in the forced swimming test (FST) and tail suspension test (TST) to evaluate the antidepressant effect of MECC. Also, the hole board test (HBT) and elevated plus maze (EPM) were conducted to examine anxiolytic activities. In contrast, the open field test (OFT) and hole cross test (HCT) were employed to evaluate sleeping disorders. RESULTS: Alkaloids, glycosides, flavonoids, terpenoids, coumarins, and tannins are only a few secondary metabolites identified in MECC by qualitative and quantitative phytochemical investigations. The oral administration of MECC considerably shortened the immobility duration during FST and TST. Encouraging dose-dependent anxiolytic effects were also observed in all relevant experiments compared to the control. Additionally, during the OFT and HCT assessment, a noteworthy decline in the locomotor activities of the experimental animals was observed. CONCLUSIONS: The results of this investigation suggest that the Chaetocarpus castanocarpus bark is a possible source of therapeutic candidates for treating neurological disorders. [ABSTRACT FROM AUTHOR]

Objective: To review and summarize the pharmacology of the antiepileptic drug (AED), levetiracetam (LEV), and to discuss its clinical utility in dogs and cats. Data Sources: Veterinary and human peer‐reviewed medical literature and the authors' clinical experience. Summary: LEV is an AED with mechanisms of action distinct from those of other AEDs. In people and small animals, LEV exhibits linear kinetics, excellent oral bioavailability, and minimal drug–drug interactions. Serious side effects are rarely reported in any species. LEV use is gaining favor for treating epilepsy in small animals and may have wider clinical applications in patients with portosystemic shunts, neuroglycopenia, and traumatic brain injury. In people, LEV may improve cognitive function in patients with dementia. Conclusion: LEV is a well‐tolerated AED with well‐documented efficacy in human patients. Although its use is becoming more common in veterinary medicine, its role as a first‐line monotherapy in small animal epileptics remains to be determined. This review of the human and animal literature regarding LEV describes its role in epileptic people and animals as well as in other disease states and provides recommendations for clinical usage. [ABSTRACT FROM AUTHOR]

G protein-coupled receptor 120 (GPR120, Ffar4) is a sensor for long-chain fatty acids including omega-3 polyunsaturated fatty acids (n-3 PUFAs) known for beneficial effects on inflammation, metabolism, and mood. GPR120 mediates the anti-inflammatory and insulin-sensitizing effects of n-3 PUFAs in peripheral tissues. The aim of this study was to determine the impact of GPR120 stimulation on microglial reactivity, neuroinflammation and sickness- and anxiety-like behaviors by acute proinflammatory insults. We found GPR120 mRNA to be enriched in both murine and human microglia, and in situ hybridization revealed GPR120 expression in microglia of the nucleus accumbens (NAc) in mice. In a manner similar to or exceeding n-3 PUFAs, GPR120 agonism (Compound A, CpdA) strongly attenuated lipopolysaccharide (LPS)-induced proinflammatory marker expression in primary mouse microglia, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibited nuclear factor-ĸB translocation to the nucleus. Central administration of CpdA to adult mice blunted LPS-induced hypolocomotion and anxiety-like behavior and reduced TNF-α, IL-1β and IBA-1 (microglia marker) mRNA in the NAc, a brain region modulating anxiety and motivation and implicated in neuroinflammation-induced mood deficits. GPR120 agonist pre-treatment attenuated NAc microglia reactivity and alleviated sickness-like behaviors elicited by central injection TNF-α and IL-1β. These findings suggest that microglial GPR120 contributes to neuroimmune regulation and behavioral changes in response to acute infection and elevated brain cytokines. GPR120 may participate in the protective action of n-3 PUFAs at the neural and behavioral level and offers potential as treatment target for neuroinflammatory conditions. Highlights: GPR120 is enriched in murine and human microglia. Central GPR120 agonism decreases microglia activation and anxiety- and sickness-like behaviors in response to LPS. GPR120 agonism attenuates nucleus accumbens microglia reactivity and behavioral responses to central cytokine administration. [ABSTRACT FROM AUTHOR]

Locomotor recovery after spinal cord injury (SCI) remains an unmet challenge. Nerve transfer (NT), the connection of a functional/expendable peripheral nerve to a paralyzed nerve root, has long been clinically applied, aiming to restore motor control. However, outcomes have been inconsistent, suggesting that NT-induced neurological reinstatement may require activation of mechanisms beyond motor axon reinnervation (our hypothesis). We previously reported that to enhance rat locomotion following T13-L1 hemisection, T12-L3 NT must be performed within timeframes optimal for sensory nerve regrowth. Here, T12-L3 NT was performed for adult female rats with subacute (7–9 days) or chronic (8 weeks) mild (SCImi: 10 g × 12.5 mm) or moderate (SCImo: 10 g × 25 mm) T13-L1 thoracolumbar contusion. For chronic injuries, T11-12 implantation of adult hMSCs (1-week before NT), post-NT intramuscular delivery of FGF2, and environmentally enriched/enlarged (EEE) housing were provided. NT, not control procedures, qualitatively improved locomotion in both SCImi groups and animals with subacute SCImo. However, delayed NT did not produce neurological scale upgrading conversion for SCImo rats. Ablation of the T12 ventral/motor or dorsal/sensory root determined that the T12-L3 sensory input played a key role in hindlimb reanimation. Pharmacological, electrophysiological, and trans-synaptic tracing assays revealed that NT strengthened integrity of the propriospinal network, serotonergic neuromodulation, and the neuromuscular junction. Besides key outcomes of thoracolumbar contusion modeling, the data provides the first evidence that mixed NT-induced locomotor efficacy may rely pivotally on sensory rerouting and pro-repair neuroplasticity to reactivate neurocircuits/central pattern generators. The finding describes a novel neurobiology mechanism underlying NT, which can be targeted for development of innovative neurotization therapies. [ABSTRACT FROM AUTHOR]

In experiments on HepG2 cells, we studied the effect of the original domestic neurotropic drugs omberacetam, fabomotizole, and ethylmethylhydroxypyridine succinate (EMHPS) (1-500 μM) on the activity and content of organic anion transporting polypeptides OATP1B1 and OATP1B3. It was shown that omberacetam (500 μM) increased the content of OATP1B1 and OATP1B3, fabomotizole did not affect the level of both transporters, and EMHPS (500 μM) increased the content of OATP1B1 compared to the control and did not affect the level of OATP1B3. The tested substances also reduced the OATP1B1/OATP1B3 ratio, as evidenced by a decrease in the penetration of atorvastatin, a substrate of the transporters, into HepG2 cells in the presence of omberacetam (100-500 μM), fabomotizole (500 μM), and EMHPS (10-500 μM). Evaluation of clinical significance of the obtained results, according to the FDA approach based on the calculation of the Cmax/IC50 ratio, showed that the effect of the tested substances on OATP1B1/OATP1B3 is clinically insignificant. [ABSTRACT FROM AUTHOR]

Methylphenidate (MPD) is a psychostimulant used to treat attention deficit hyperactivity disorder. MPD exerts its neurocognitive effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the neuronal synapse. This study recorded from adult freely behaving rats a total of 1170 neurons, 403 from the ventral tegmental area (VTA), 409 from locus coeruleus (LC), and 356 from dorsal raphe (DR) nucleus, which are the main sources of DA, NE, and 5-HT to the mesocorticolimbic circuitry, respectively. Electrophysiological and behavioral activities were recorded simultaneously following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0 mg/kg MPD. The uniqueness of this study is the evaluation of neuronal activity based on the behavioral response to chronic MPD. Animals received daily saline or MPD administration on experimental days 1–6 (ED1–6), followed by a 3-day wash-out period, and then MPD rechallenge on ED10. Each chronic MPD dose elicits behavioral sensitization in some animals, while in others, behavioral tolerance. Neuronal excitation following chronic MPD was observed in brains areas of animals exhibiting behavioral sensitization, while neuronal attenuation following chronic MPD was observed in those animals expressing behavioral tolerance. DR neuronal activity was most affected in response to acute and chronic MPD administration and responded differently compared to the neurons recorded from VTA and LC neurons at all doses. This suggests that although not directly related, DR and 5-HT are involved in the acute and chronic effects of MPD in adult rats, but exhibit a different role in response to MPD. [ABSTRACT FROM AUTHOR]

Abstract Background Ofatumumab is the first monoclonal antibody developed specifically for treating relapsed multiple sclerosis (RMS). This disease (Multiple Sclerosis) includes relapsing–remitting multiple sclerosis (RRMS), a chronic autoimmune illness that affects the central nervous system (CNS), including the brain and spinal cord. The purpose of this study is to determine whether Ofatumumab is efficacious and safe in the treatment of relapsing–remitting multiple sclerosis. Methods An analysis of studies comparing Ofatumumab with placebo in people with relapsing‐remitting multiple sclerosis was done in accordance with PRISMA guidelines. We looked up information in MEDLINE, SciSearch, BIOSIS Previews, Derwent Drug File, Embase, and International Pharmaceutical Abstracts. In patients with relapsing–remitting multiple sclerosis, randomized double‐blind and non‐randomized trials contrasting Ofatumumab with placebo were found by two independent investigators. Utilizing Review Manager 5.4.1, data were examined. The main results were total gadolinium‐enhancing (Gd+) T1 lesions, annualized relapse rate, and new or expanding total T2 lesions. Secondary outcomes concentrated on general adverse events and adverse events related to infections. Results Three studies were included involving 334 patients, and the meta‐analysis indicated that Ofatumumab showed good efficacy and safety in patients with relapsing forms of multiple sclerosis. The annual rate of relapse was significantly reduced by Ofatumumab (OR 0.51; 95% CI 0.27, 0.98; P = 0.04). Ofatumumab reduced the number of gadolinium‐enhancing (Gd+) T1 lesions per scan (Mean difference −0.59; 95% CI −0.63, −0.55; P

This document is an editorial published in Frontiers in Neuroscience titled "Pharmaceutical strategies to prevent, treat, and recover: advances and challenges in ischemic stroke and hemorrhagic stroke." The editorial discusses the urgent need for pharmaceutical therapies for both ischemic and hemorrhagic stroke, as current therapeutic strategies are time-sensitive. The document highlights the importance of exploring the complex regulation network after stroke to develop new effective treatment strategies. It also mentions various articles included in the research topic, which cover pathological mechanisms, new therapeutic entities, and other aspects of stroke. The editorial emphasizes the diverse facets of stroke prevention, treatment, and recovery and the potential of emerging areas such as new drug delivery systems. [Extracted from the article]

Electrophysiological methods of research are widely used in neurobiology. To assess the bioelectrical activity of the brain in small laboratory animals, electrocorticography (ECoG) is most often used, which allows the recording of signals directly from the cerebral cortex. To date, a number of methodological approaches to the manufacture and implantation of ECoG electrodes have been proposed, the complexity of which is determined by experimental tasks and logistical capabilities. Existing methods for analyzing bioelectrical signals are used to assess the functional state of the nervous system in test animals, as well as to identify correlates of pathological changes or pharmacological effects. The review presents current areas of applications of ECoG in neuropharmacological studies in small laboratory animals. Traditionally, this method is actively used to study the antiepileptic activity of new molecules. However, the possibility of using ECoG to assess the neuroprotective activity of drugs in models of traumatic, vascular, metabolic, or neurodegenerative CNS damage remains clearly underestimated. Despite the fact that ECoG has a number of disadvantages and methodological difficulties, the recorded data can be a useful addition to traditional molecular and behavioral research methods. An analysis of the works in recent years indicates a growing interest in the method as a tool for assessing the pharmacological activity of psychoactive drugs, especially in combination with classification and prediction algorithms.

As the incidence of neurodegeneration and cancer fatalities remains high, researchers are focusing their efforts on discovering and developing effective medications, especially plant-based drugs, against these diseases. Hence, this research aimed to investigate the neuropharmacological potentials of aerial parts of Tetrastigma leucostaphyllum, employing some behavioral models, while the antiproliferative effect was explored against a panel of cancer cell lines (MGC-803, A549, U-251, HeLa and MCF-7) using a colorimetric assay. In addition, active extracts were analyzed by GC–MS technique to identify the active compounds, where some selective compounds were docked with the particular pure proteins to check their binding affinity. Results from neuropharmacological research indicated that the total extract and its fractions may be effective (p = 0.05, 0.01, and 0.001, respectively) at doses of 100, 200, and 400 mg/kg of animal body weight. The greatest antidepressant and anxiolytic effects were found in the n-hexane fraction. The n-haxane fraction also exhibited the highest cytotoxicity against the U-251 cell line (IC5014.3 μg/mL), followed by the A549, MG-803, HeLa, and MCF-7 cell lines, respectively. From the n-hexane fraction, ten chemicals were detected using the GC–MS method. Additionally, the in-silico research revealed interactions between the n-hexane fractions' identified compounds and the antidepressant, anxiolytic, and cytotoxic receptors. The molecules showed binding affinities that ranged from 4.6 kcal/mol to 6.8 kcal/mol, which indicates the likelihood that they would make good drug candidates. This study highlighted the plant's neuropharmacological and cytotoxic properties, however, more research is needed to determine the etymological origin of these effects.