Central Nervous System Disorders Research Articles

Betahistine's Neuroprotective Actions against Lipopolysaccharide-Induced Neurotoxicity: Insights from Experimental and Computational Studies.

Histamine H3 receptor (H3R) antagonists, such as betahistine (BHTE), have shown significant potential in treating central nervous system (CNS) disorders due to their neuroprotective properties. This study investigated BHTE's effects on lipopolysaccharide (LPS)-induced neurotoxicity, which is associated with neuroinflammation and neurodegeneration. Rats were divided into groups and pre-treated with BHTE (5 or 10 mg/kg, p.o.) for 30 days, followed by LPS administration (1 mg/kg, i.p.) for 4 consecutive days to induce neurotoxicity. LPS exposure resulted in cognitive impairment, as evidenced by performance deficits in maze tests, and a significant reduction in brain acetylcholine (ACh) levels. Additionally, LPS led to increased neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis. Pre-treatment with BHTE effectively counteracted these effects, improving cognitive performance and restoring ACh levels. BHTE significantly reduced LPS-induced increases in pro-inflammatory markers (COX-2, TNF-α, and IL-6) while enhancing anti-inflammatory cytokines (IL-10 and TGF-β1). Furthermore, BHTE improved mitochondrial function by increasing enzyme levels (MRCC-I, II, and IV) and boosted anti-apoptotic (Bcl-2) and antioxidant defenses (GSH and catalase). BHTE also reduced apoptosis markers, including pro-apoptotic protein caspase-3, and oxidative stress marker malondialdehyde (MDA). Molecular modeling studies revealed that BHTE effectively binds to key enzymes involved in neuroinflammation and apoptosis (AChE, COX-2, and caspase-3), with binding free energies between 4 and 5 kcal/mol, interacting with critical residues. These findings underscore BHTE's multifaceted neuroprotective effects against LPS-induced neurotoxicity, offering potential therapeutic avenues for managing neuroinflammation and related neurodegenerative disorders.

Classification of optic neuritis in neuromyelitis optica spectrum disorders (NMOSD) on MRI using CNN with transfer learning and manipulation of pre-processing on augmentation

Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is an autoimmune central nervous system disorder in humans that commonly causes inflammatory demyelination in the optic nerves and spinal cord. Inflammation in the optic nerves is termed optic neuritis (ON). ON is a common clinical presentation; however, it is not necessarily present in all NMOSD patients. ON in NMOSD can be relapsing and result in severe vision loss. To the best of our knowledge, no study utilises deep learning to classify ON changes on MRI among patients with NMOSD. Therefore, this study aims to deploy eight state-of-the-art CNN models (Inception-v3, Inception-ResNet-v2, ResNet-101, Xception, ShuffleNet, DenseNet-201, MobileNet-v2, and EfficientNet-B0) with transfer learning to classify NMOSD patients with and without chronic ON using optic nerve magnetic resonance imaging. This study also investigated the effects of data augmentation before and after dataset splitting on cropped and whole images. Both quantitative and qualitative assessments (with Grad-Cam) were used to evaluate the performances of the CNN models. The Inception-v3 was identified as the best CNN model for classifying ON among NMOSD patients, with accuracy of 99.5%, sensitivity of 98.9%, specificity of 93.0%, precision of 100%, NPV of 99.0%, and F1-score of 99.4%. This study also demonstrated that the application of augmentation after dataset splitting could avoid information leaking into the testing datasets, hence producing more realistic and reliable results.

Advancements in strategies for overcoming the blood-brain barrier to deliver brain-targeted drugs.

The blood-brain barrier is known to consist of a variety of cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates the pharmacological treatment of central nervous system disorders as most drugs are unable to penetrate the blood-brain barrier on the basis of their own structural properties. This dramatically diminished the therapeutic effect of the drug and compromised its biosafety. In response, a number of drugs are often delivered to brain lesions in invasive ways that bypass the obstruction of the blood-brain barrier, such as subdural administration, intrathecal administration, and convection-enhanced delivery. Nevertheless, these intrusive strategies introduce the risk of brain injury, limiting their clinical application. In recent years, the intensive development of nanomaterials science and the interdisciplinary convergence of medical engineering have brought light to the penetration of the blood-brain barrier for brain-targeted drugs. In this paper, we extensively discuss the limitations of the blood-brain barrier on drug delivery and non-invasive brain-targeted strategies such as nanomedicine and blood-brain barrier disruption. In the meantime, we analyze their strengths and limitations and provide outlooks on the further development of brain-targeted drug delivery systems.

Central Nervous System Disorders with Auto-Antibodies in People Living with HIV.

People living with HIV (PLWH) may present atypical neurological complications. Recently, autoimmune manifestations of the central nervous system (CNS) have been described. We retrospectively described the features of PLWH presenting with acute neurological symptoms with positive anti-CNS antibodies. We analyzed relevant CSF characteristics. Twelve patients were identified, with demyelinating, inflammatory, or no MRI lesions. We observed CSF inflammatory features. Aspecific CSF anti-CNS antibodies were found in all subjects and a specific antibody (second-level blotting panel) was found in one. The cases presented a slow resolution of symptoms with sequelae. More studies are needed to better describe the spectrum and prognosis of autoimmune CNS diseases in PLWH.

Modulation of miR-466d-3p on Wnt signaling pathway in response to DEPs-induced blood-brain barrier disruption

BackgroundDiesel exhaust particles (DEPs), a predominant component of ambient particulate matter (PM), are classified as ultrafine particles with the capacity to penetrate the cerebral blood-brain barrier (BBB). This penetration is implicated in the pathogenesis of central nervous system (CNS) disorders. The integrity of the BBB is inextricably linked to cerebrovascular homeostasis and the development of neurodegenerative disease, highlighting the importance of studying the effects and mechanisms of DEPs on BBB function damage. Methods and resultsUtilizing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we explored the detrimental effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an upregulation in the secretion of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, and diminished tight junction (TJ) protein expression. Microarray analysis revealed that 23 miRNAs were upregulated and 11 were downregulated in response to a 50 μg/mL DEPs treatment, with miR-466d-3p being notably differentially expressed. Wnt3 was identified as a target of miR-466d-3p, with the Wnt signaling pathway being significantly enriched. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/β-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and β-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression. ConclusionsOur study further confirmed that DEPs can induce the disruption of BBB integrity through inflammatory processes. We identified alterations in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a key regulator of tight junction (TJ) proteins, essential for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ β-catenin and Wnt/PCP signaling pathway can be activated by DEPs and are regulated by miR-466d-3p. Under the combined effects of Wnt/PCP and inflammation, there is an ultimate increase in BBB hyperpermeability.

Inhibiting the NF-κB/DRP1 Axis Affords Neuroprotection after Spinal Cord Injury via Inhibiting Polarization of Pro-Inflammatory Microglia.

Spinal cord injury (SCI) is considered a central nervous system (CNS) disorder. Nuclear factor kappa B (NF-κB) regulates inflammatory responses in the CNS and is implicated in SCI pathogenesis. The mechanism(s) through which NF-κB contributes to the neuroinflammation observed during SCI however remains unclear. SCI rat models were created using the weight drop method and separated into Sham, SCI and SCI+NF-κB inhibitor groups (n = 6 rats per-group). We used Hematoxylin-Eosin Staining (H&E) and Nissl staining for detecting histological changes in the spinal cord. Basso-Beattie-Bresnahan (BBB) behavioral scores were utilized for assessing functional locomotion recovery. Mouse BV2 microglia were exposed to lipopolysaccharide (LPS) to mimic SCI-induced microglial inflammation in vitro. Inhibition of NF-κB using JSH-23 alleviated inflammation and neuronal injury in SCI rats' spinal cords, leading to improved locomotion recovery (p < 0.05). NF-κB inhibition reduced expression levels of CD86, interleukin-6 (IL-6), IL-1β, and inducible Nitric Oxide Synthase (iNOS), and improved expression levels of CD206, IL-4, and tissue growth factor-beta (TGF-β) in both LPS-treated microglia and SCI rats' spinal cords (p < 0.05). Inhibition of NF-κB also effectively suppressed mitochondrial fission, evidenced by the reduced phosphorylation of dynamin-related protein 1 (DRP1) at Ser616 (p < 0.001). We show that inhibition of the NF-κB/DRP1 axis prevents mitochondrial fission and suppresses pro-inflammatory microglia polarization, promoting neurological recovery in SCI. Targeting the NF-κB/DRP1 axis therefore represents a novel approach for SCI.

Tackling Neuroinflammation in Cognitive Disorders with Single-Targeted and Multi-Targeted Histamine H3 Receptor Modulators.

Neuroinflammation is a process involved in a variety of central nervous system (CNS) diseases and is being increasingly recognized as a key mediator of cognitive impairments. Neuroinflammatory responses including glial activation, increased production of proinflammatory cytokines, and aberrant neuronal signaling, contribute to cognitive dysfunctions. Histamine is a key peripheral inflammatory mediator, but plays an important role in neuroinflammatory processes as well. The unique localization of histamine H3 receptor (H3R) in the CNS along with the modulation of the release of other neurotransmitters via its action on heteroreceptors on non-histaminergic neurons have led to the development of several H3R ligands for various brain diseases. H3R antagonists/ inverse agonists have revealed potential to treat diverse neuroinflammatory CNS disorders, including neurodegenerative diseases, attention-deficit hyperactivity syndrome and schizophrenia. In this mini review, we provide a brief overview on the crucial involvement of the histaminergic transmission in the neuroinflammatory processes underlying these cognitive disorders, with a special focus on H3R involvement. The anti-neuroinflammatory potential of single-targeted and multi-targeted H3R antagonists/inverse agonists for the treatment of these conditions is discussed here.

Platelet-rich plasma protects hippocampal neurons and memory functions in a rat model of vascular dementia.

Platelet-rich plasma (PRP) is a promising biomaterial rich in bioactive growth factors, offering potential as a therapeutic agent for various diseases. However, its effectiveness in central nervous system disorders like vascular dementia (VaD) remains underexplored. This study investigated the potential of PRP to mitigate VaD progression in vivo. A rat model of VaD was established via bilateral common carotid artery occlusion and hypovolemia operation. Rats were randomly assigned to receive either PRP or platelet-poor plasma (PPP)-the latter being a byproduct of PRP preparation and used as a reference standard-resulting in the groups designated as 'operated group (OP)+PRP' and 'OP+PPP', respectively. PRP or PPP (500 μl) was administered intraperitoneally on the day of the operation and postoperative days 2, 4, 6, and 8. Cognitive function was assessed using the Y-maze, Barnes maze, and passive avoidance tests. On postoperative day 8, hippocampal samples were subjected to histological and semi-quantitative analyses. OP exhibited significant memory decline compared to controls, while the 'OP+PRP' group showed notable improvement. Histological analysis revealed increased neuronal loss and neuroinflammation in OP hippocampi, mitigated in 'OP+PRP'. Semi-quantitative analysis showed decreased expression of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) in OP, restored in 'OP+PPP' and further in 'OP+PRP'. These results highlight PRP's protective effects against VaD-induced hippocampal damage and cognitive impairment, partially attributed to BDNF/TrkB pathway upregulation.

Fibrin-Polycaprolactone Scaffolds for the Differentiation of Human Neural Progenitor Cells into Dopaminergic Neurons.

Parkinson's disease (PD), a progressive central nervous system disorder marked by involuntary movements, poses a significant challenge in neurodegenerative research due to the gradual degeneration of dopaminergic (DA) neurons. Early diagnosis and understanding of PD's pathogenesis could slow disease progression and improve patient management. In vitro modeling with DA neurons derived from human-induced pluripotent stem cell-derived neural progenitor cells (NPCs) offers a promising approach. These neurons can be cultured on electrospun (ES) nanofibrous polycaprolactone (PCL) scaffolds, but PCL's hydrophobic nature limits cell adhesion. We investigated the ability of ES PCL scaffolds coated with hydrophilic extracellular matrix-based biomaterials, including cell basement membrane proteins, Matrigel, and Fibrin, to enhance NPC differentiation into DA neurons. We hypothesized that fibrin-coated scaffolds would maximize differentiation based on fibrin's known benefits in neuronal tissue engineering. The scaffolds both coated and uncoated were characterized using scanning electron microscopy (SEM), transmission electron microscopy, Fourier transform infrared spectroscopy-attenuated total reflectance, and dynamic mechanical analysis to assess their properties. NPCs were seeded on the coated scaffolds, differentiated, and matured into DA neurons. Immunocytochemistry targeting tyrosine hydroxylase (TH) and SEM confirmed DA neuronal differentiation and morphological changes. Electrophysiology via microelectrode array recorded their neuronal firing. Results showed enhanced neurite extension, increased TH expression, and active electrical activity in cells on fibrin-coated scaffolds. Diluted fibrin coatings particularly promoted more pronounced neuronal differentiation and maturation. This study introduces a novel tissue-on-a-chip platform for neurodegenerative disease research using DA neurons.

Unusual demyelinating disease in a patient with HIV infection.

Demyelinating central nervous system (CNS) disorders are a diverse group of conditions characterised by damage to the myelin sheath. These include not only primary autoimmune disorders such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), but secondary demyelinating conditions caused by infection and neoplasm, where immunosuppressive therapy may worsen the condition or delay definitive treatment. We describe a young man with an unusual presentation of CNS demyelinating disease associated with HIV infection and positive syphilis serology. MRI brain and spine showed a demyelinating tumefactive lesion accompanied by longitudinal extensive transverse myelitis, and we initially suspected NMOSD. However anti-aquaporin 4 antibodies were negative, going against a diagnosis of NMOSD and he then tested positive for HIV which led us to consider TB myelitis, neurosyphilis and HIV vacuolar myelopathy. He was commenced on highly active retroviral therapy and treated with steroids and immunosuppression. He did not respond to treatment as expected so a brain biopsy was required to narrow the differential. Brain biopsy initially raised the possibility of progressive multifocal leukoencephalopathy which is associated with infection with the John Cunningham (JC) virus. Ultimately JC Virus PCR on the biopsy was negative, the final report suggesting nonspecific active chronic inflammation. We detail his clinical course and the diagnostic challenges along the way.

Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders.

In the post-COVID-19 era, treatment options for potential SARS-CoV-2 outbreaks remain limited. An increased incidence of central nervous system (CNS) disorders has been observed in long-term COVID-19 patients. Understanding the shared molecular mechanisms between these conditions may provide new insights for developing effective therapies. This study developed an integrative drug-repurposing framework for COVID-19, leveraging comorbidity data with CNS disorders, network-based modular analysis, and dynamic perturbation analysis to identify potential drug targets and candidates against SARS-CoV-2. We constructed a comorbidity network based on the literature and data collection, including COVID-19-related proteins and genes associated with Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. Functional module detection and annotation identified a module primarily involved in protein synthesis as a key target module, utilizing connectivity map drug perturbation data. Through the construction of a weighted drug-target network and dynamic network-based drug-repurposing analysis, ubiquitin-carboxy-terminal hydrolase L1 emerged as a potential drug target. Molecular dynamics simulations suggested pregnenolone and BRD-K87426499 as two drug candidates for COVID-19. This study introduces a dynamic-perturbation-network-based drug-repurposing approach to identify COVID-19 drug targets and candidates by incorporating the comorbidity conditions of CNS disorders.

Amplitude-integrated electroencephalography monitoring results of hospitalized neonates in plateau areas

To investigate the amplitude-integrated electroencephalography (aEEG) monitoring results of hospitalized neonates in plateau areas. A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology, Kunming Children's Hospital, and received aEEG monitoring from January 2020 to December 2022. According to the aEEG monitoring results, they were divided into a normal aEEG group and an abnormal aEEG group. The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases, as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities. Among the 5 945 neonates, the aEEG abnormality rate was 19.28% (1 146/5 945), with an abnormality rate of 29.58% (906/3 063) in critically ill neonates and 8.33% (240/2 882) in non-critically ill neonates (P<0.05). The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77% (79/130), followed by those with central nervous system disorders [42.22% (76/180)] and preterm infants [35.53% (108/304)]. Compared with the normal aEEG group, the abnormal aEEG group had significantly lower age and gestational age, as well as a significantly lower birth weight of preterm infants (P<0.05). Among the 1 146 neonates with aEEG abnormalities, the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates (52.09%), background activity abnormalities in 294 neonates (25.65%), and epileptiform activity in 255 neonates (22.25%), and there were 902 neonates (78.71%) with abnormal clinical manifestations. The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51% and 92.50%, respectively. In plateau areas, there is a relatively high rate of aEEG abnormalities among hospitalized neonates, particularly in critically ill neonates and those with smaller gestational ages and younger ages, suggesting a high risk of brain injury. Therefore, routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities, the decision-making in treatment, and the formulation of brain protection strategies.

The role of gastrodin in the management of CNS-related diseases: Underlying mechanisms to therapeutic perspectives.

Central nervous system (CNS)-related diseases have a high mortality rate, are a serious threat to physical and mental health, and have always been an important area of research. Gastrodin, the main active metabolite of Gastrodia elata Blume, used in Chinese medicine and food, has a wide range of pharmacological effects, mostly related to CNS disorders. This review aims to systematically summarize and discuss the effects and underlying mechanisms of gastrodin in the treatment of CNS diseases, and to assess its potential for further development as a lead drug in both biomedicine and traditional Chinese medicine. Studies on the pharmacological effects of gastrodin on the CNS indicate that it may exert anti-neurodegenerative, cerebrovascular protective, and ameliorative effects on diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression and anxiety, and sleep disorders through various mechanisms. To date, 110 gastrodin products have been approved for clinical use, but further multicenter clinical case-control studies are relatively scarce. Preclinical studies have confirmed that gastrodin can be used to treat CNS-related disorders. However, important concerns need to be addressed in the context of likely non-specific, assay interfering effects when gastrodin is studied using in vitro and in silico approaches, calling for a systematic assessment of the evidence to date. High-quality clinical trials should have priority to evaluate the therapeutic safety and clinical efficacy of gastrodin. Further experimental research using appropriate in vivo models is also needed, focusing on neurodegenerative diseases, cerebral ischemic and hypoxic diseases, brain damage caused by methamphetamine or heavy metals, and epilepsy.

Central Nervous System Disorders of Marine Mammals: Models for Human Disease?

This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal "counterparts" in a dual "One Health" and "Translational Medicine" perspective. Within this challenging context, special emphasis is placed upon Alzheimer's disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by "Subacute Sclerosing Panencephalitis" (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a "brain-only" form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human "analogues".

Identification and Characterization of a Blood-Brain Barrier Penetrant Inositol Hexakisphosphate Kinase (IP6K) Inhibitor.

Inositol hexakisphosphate kinases (IP6Ks) have been studied for their role in glucose homeostasis, metabolic disease, fatty liver disease, chronic kidney disease, neurological development, and psychiatric disease. IP6Ks phosphorylate inositol hexakisphosphate (IP6) to the pyrophosphate, 5-diphosphoinositol-1,2,3,4,6-pentakisphosphate (5-IP7). Most of the currently known potent IP6K inhibitors contain a critical carboxylic acid which limits blood-brain barrier (BBB) penetration. In this work, the synthesis and testing of a variety of carboxylic acid isosteres resulted in several new compounds with improved BBB penetration. The most promising compound has an IP6K1 IC50 of 16 nM with an improved brain/plasma ratio and a favorable pharmacokinetic profile. This series of brain penetrant compounds may be used to investigate the role of IP6Ks in CNS disorders.

Pharmacological inhibition of histone deacetylase alleviates chronic unpredictable stress induced atherosclerosis and endothelial dysfunction via upregulation of BDNF

Long-term stress is a significant risk factor for cardiovascular diseases, including atherosclerosis and endothelial dysfunction. Moreover, prolonged stress has shown to negatively regulate central BDNF expression. The role of central BDNF in CNS disorders is well studied until recently the peripheral BDNF was also found to be involved in endothelial function regulation and atherosclerosis. The peripheral BDNF and its role in chronic stress-induced atherosclerosis and endothelial dysfunction remain unclear. Therefore, we aimed to elucidate the role of BDNF and its modulation by the HDAC inhibitor valproic acid (VA) in chronic unpredictable stress (CUS)-induced atherosclerosis and endothelial dysfunction. We demonstrated that a 10-week CUS mouse model substantially decreases central and peripheral BDNF expression, resulting in enhanced serum lipid indices, plaque deposition, fibrosis, and CD68 expression in thoracic aortas. Further, parameters associated with endothelial dysfunction such as increased levels of endothelin-1 (ET-1), adhesion molecules like VCAM-1, M1 macrophage markers, and decreased M2 macrophage markers, eNOS expression, and nitrite levels in aortas, were also observed. VA (50 mg/kg, 14 days, i. p.) was administered to mice following 8 weeks of CUS exposure until the end of the experimental procedure. VA significantly prevented the decrease in BDNF, eNOS and nitrite levels, reduced lesion formation and fibrosis in thoracic aortas and increased ET-1, and VCAM-1 followed by M2 polarization in VA-treated mice. The study highlights the potential of epigenetic modulation of BDNF as a therapeutic target, in stress-induced cardiovascular pathologies and suggests that VA could be a promising agent for mitigating CUS-induced endothelial dysfunction and atherosclerosis by BDNF modulation.

A Comprehensive Review of the Pharmacological Effects of Genus Ferula on Central Nervous System Disorders.

Plants of the genus Ferula have long been used to treat neurological diseases such as Alzheimer's disease (AD), pain, depression, and seizures. The main compounds include coumarins, monoterpenes, sulfide compounds, and polyphenol compounds, which can improve the functioning of the nervous system. This article has been compiled with the aim of collecting evidence and articles related to the Ferula effects on central nervous system disease. This review article was prepared by searching the terms Ferula and analgesic, anticonvulsant, antidepressant, anti-multiple sclerosis, anti-dementia, and neuroprotective effects.The relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Genus Ferula has a protective effect on nerve cells by reducing cytokines such as IL-6, IL- 1b, and TNF-α. Therefore, the effects of Ferula plants and their effective ingredients can be used to prevent or improve diseases that destroy the nervous system. The members of this genus play a role in strengthening and improving the antioxidant system, reducing the level of oxidative stress, and inhibiting or reducing inflammatory factors in the nervous system. Although the effects of several species of Ferula on the nervous system have been investigated, most studies have not clearly identified the molecular mechanisms as well as the specific functional regions of the brain. The present study was compiled in order to investigate different aspects of the effects of Ferula plants on the central nervous system.

Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders.

Cyclic adenosine monophosphates (cAMP) and cyclic guanosine monophosphate (cGMP) are two essential second messengers, which are hydrolyzed by phosphodiesterase's (PDEs), such as PDE-2. Pharmacological inhibition of PDE-2 (PDE2A) in the central nervous system improves cAMP and cGMP signaling, which controls downstream proteins related to neuropsychiatric, neurodegenerative, and neurodevelopmental disorders. Considering that there are no specific treatments for these disorders, PDE-2 inhibitors' development has gained more attention in the recent decade. There is high demand for developing new-generation drugs targeting PDE2 for treating diseases in the central nervous and peripheral systems. This review summarizes the relationship between PDE-2 with neuropsychiatric, neurodegenerative, and neurodevelopmental disorders as well as its possible treatment, mainly involving inhibitors of PDE2.

Quantification of Glycyrrhizic Acid in FLEGMEN-SIP Capsules Using High-Performance Liquid Chromatography for CNS Disorders

Background: Neurological diseases affect over one billion people globally, presenting a significant health burden, especially for vulnerable populations. The FLEGMEN-SIP capsule was developed as a treatment option for central nervous system disorders, containing glycyrrhizic acid as its primary active ingredient. This study aims to quantify the glycyrrhizic acid content in FLEGMEN-SIP capsules using high-performance liquid chromatography (HPLC) to ensure compliance with therapeutic standards. Methods: The study utilized HPLC to quantify glycyrrhizic acid in FLEGMEN-SIP capsules. The capsules contain a dry extract derived from Phlomis regelii, Leonurus turkestanicus, Mentha piperita, and Glycyrrhiza glabra, with glycyrrhizic acid comprising 1.39% of the dry extract. Samples were prepared by dissolving 0.050 g of the drug in the mobile phase and filtered using a 0.45 µm membrane filter. The HPLC system included a Zorbax column and UV detection at 254 nm. The analysis was repeated five times for accuracy. Results: The glycyrrhizic acid content in FLEGMEN-SIP capsules was determined to be 0.55%, surpassing the minimum regulatory requirement of 0.4%. The chromatographic method demonstrated high reproducibility and reliability, confirming the quality and therapeutic efficacy of the capsules. Conclusion: The study validated the use of HPLC as an effective method for quantifying glycyrrhizic acid in FLEGMEN-SIP capsules. The results confirm the capsules meet regulatory standards, ensuring their suitability for treating central nervous system disorders.

Effects of Maternal SARS-CoV-2 Infection During Pregnancy on Fetal Development.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak in 2019 has necessitated investigating its potential adverse effects on pregnancy outcomes and fetal development. This study aimed to review the evidence on the impact of SARS-CoV-2 infection during pregnancy on fetal outcomes. Literatures since the outbreak of COVID-19 from PubMed and Web of Science were summarized in this narrative review, to show the effects of maternal SARS-CoV-2 infection during pregnancy on fetal development. SARS-CoV-2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal-fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS-CoV-2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth. However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes. Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes. SARS-CoV-2 infection during pregnancy activates the maternal-fetal immune interface through vertical transmission, and has short- and long-term effects on fetal development, including the central nervous system. Future long-term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes.