Central Nervous System Conditions Research Articles

A review on targeted temperature management for cardiac arrest and traumatic brain injury.

Therapeutic hypothermia inhibits organ damage by suppressing metabolism, which makes it a therapy of choice for treating various diseases. Specifically, it is often used to treat conditions involving central nervous system disorders where it is expected to positively impact functional prognosis. Although keeping the body temperature at a hypothermic level has been conventionally used, how to manage the body temperature correctly remains a topic of debate. Recently, the concept of temperature management has been proposed to improve the quality of body temperature control and avoid hyperthermia. This review focuses on the effect of temperature on the central nervous system in conditions involving central nervous system disorders and the practice of temperature management in clinical situations.

Choroid Plexus Pathophysiology.

This review examines the crucial roles of the choroid plexus (ChP) in central nervous system (CNS) pathology, emphasizing its involvement in disease mechanisms and therapeutic potential. Structural changes in the human ChP have been reported across various diseases in case reports and descriptive work, but studies have yet to pin down the physiological relevance of these changes. We highlight primary pathologies of the ChP, as well as their significance in neurologic disorders, including stroke, hydrocephalus, infectious diseases, and neurodegeneration. Synthesizing recent research, this review positions the ChP as a critical player in CNS homeostasis and pathology, advocating for enhanced focus on its mechanisms to unlock new diagnostic and treatment strategies and ultimately improve patient outcomes in CNS diseases. Whether acting as a principal driver of disease, a gateway for pathogens into the CNS, or an orchestrator of neuroimmune processes, the ChP holds tremendous promise as a therapeutic target to attenuate a multitude of CNS conditions.

Intrathecal Immunoselective Nanopheresis for Alzheimer’s Disease: What and How? Why and When?

Nanotechnology is transforming therapeutics for brain disorders, especially in developing drug delivery systems. Intrathecal immunoselective nanopheresis with soluble monoclonal antibodies represents an innovative approach in the realm of drug delivery systems for Central Nervous System conditions, especially for targeting soluble beta-amyloid in Alzheimer’s disease. This review delves into the concept of intrathecal immunoselective nanopheresis. It provides an overall description of devices to perform this technique while discussing the nanotechnology behind its mechanism of action, its potential advantages, and clinical implications. By exploring current research and advancements, we aim to provide a comprehensive understanding of this novel method, addressing the critical questions of what it is, how it works, why it is needed, and when it should be applied. Special attention is given to patient selection and the optimal timing for therapy initiation in Alzheimer’s, coinciding with the peak accumulation of amyloid oligomers in the early stages. Potential limitations and alternative targets beyond beta-amyloid and future perspectives for immunoselective nanopheresis are also described.

Evaluation and diagnosis of pediatric patients with dizziness.

Children experiencing dizziness frequently go unevaluated or experience delays in correct diagnosis due to systemic and inherent barriers. While most causes of pediatric dizziness do not involve the peripheral vestibular system, otolaryngologists are frequently consulted for expert opinion. This study offers a broad overview of the leading causes of pediatric dizziness and imbalance to assist otolaryngologists with evaluating and managing this challenging population. Evaluation of children with dizziness should exclude serious central nervous system conditions. Approximately 70% of nonhazardous cases of pediatric dizziness are caused by migraine-related conditions, concussion, or functional disorders. Etiologies for peripheral vestibular dysfunction include inner ear malformations and vestibular disorders more commonly seen in adults. Audiometric and vestibular testing can provide helpful information, although correct diagnosis depends on a detailed history. Otolaryngologists should be familiar with the conditions that cause dizziness in children. While most underlying causes are outside their scope of practice, understanding possible etiologies can facilitate correct diagnosis and appropriate management.

Unraveling the Role of the Glycogen Synthase Kinase-3β, Bruton's Tyrosine Kinase, and Sphingosine 1 Phosphate Pathways in Multiple Sclerosis.

Inflammation, demyelination, and neurodegeneration are symptoms of the central nervous system (CNS) condition known as Multiple sclerosis (MS). Due to its crucial function in controlling immune cell activation and inflammation, the glycogen synthase kinase-3β (GSK- 3β), Bruton's tyrosine kinase (BTK), and Sphingosine 1 phosphate (S1P) signaling pathway have become a viable target for the therapy of MS. The GSK-3β signaling system, which controls several biological target processes, including cell survival, proliferation, and inflammation, depends on the GSK-3β enzyme. In MS animal models and human studies, GSK-3β inhibition has been demonstrated to lessen demyelination and inflammation. Clinical research on MS has demonstrated that BTK inhibitors decrease inflammation and disease activity by preventing B cell activation and the subsequent release of cytokines. Clinical investigations for MS have demonstrated that S1P modulators, such as fingolimod, lower disease activity and inflammation by limiting immune cell migration to the central nervous system and preventing cytokine production. The GSK-3β /BTK/S1P signaling pathway in MS is the subject of this paper's summary and discussion of prospective treatment targets.

The multifaceted effects of fluoxetine treatment on cognitive functions.

Fluoxetine, the prototypical selective serotonin reuptake inhibitor (SSRI), is widely used to treat major depressive disorder (MDD) and a variety of other central nervous system conditions, primarily due to its established clinical safety profile. Although its efficacy in treating depression is well-recognized, the impact of fluoxetine on cognitive functions remains inconsistent and elusive. In this review, we first examine the well-substantiated biological mechanisms underlying fluoxetine's antidepressant effects, which include serotonin reuptake inhibition and activation of TrkB receptors-key to brain-derived neurotrophic factor (BDNF) signaling. Subsequently, we delve into the cognitive side effects observed in both preclinical and clinical studies, affecting domains such as memory, attention, and executive functions. While certain studies indicate cognitive improvements in patients with underlying disorders, there is also evidence of negative effects, influenced by variables like gender, duration of treatment, age, disease pathology, and the specifics of cognitive testing. Significantly, the negative cognitive outcomes reported in preclinical research often involve healthy, non-diseased animals. This review underscores the necessity for heightened caution in fluoxetine prescription and further investigation into its potentially detrimental cognitive effects, even when used prophylactically.

Reservoir-type intranasal implants for sustained release of risperidone: A potential alternative for long-term treatment of schizophrenia

To overcome the challenges of the blood-brain barrier for drug delivery to the central nervous system (CNS), intranasal implants were developed to improve the management of CNS conditions, such as schizophrenia. In the present work, we developed and characterised a drug-containing implant consisting of two parts: a core layer made from risperidone (RIS) and water-soluble polymers, including poly(vinylpyrrolidone) (PVP) and poly(ethylene glycol) (PEG), and a coating layer made of poly(caprolactone) (PCL) membrane. The obtained implants, where the core layer contained 75 % w/w risperidone, were characterised using several techniques: scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR). Moreover, the in vitro release profile of RIS was studied, showing that the PCL membrane could extend the release of RIS from 2 days up to 100 days. The in vitro release profile of the PCL-coated implant exhibited a linear release over the first 10 days, followed by a slower release rate that reached another linear phase up to 40 days. Subsequently, the drug release rates progressively slowed down. Finally, the results of in vitro biocompatibility studies indicated that the intranasal implants were biocompatible and non-cytotoxic. These findings suggest that the implants prepared in this work have the potential to provide long-acting drug delivery for targeting the brain.

An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.

Epigenetic mechanisms are crucial in regulating gene expression. These mechanisms include DNA methylation and histone modifications, like methylation, acetylation, and phosphorylation. DNA methylation is associated with gene expression suppression; however, histone methylation can stimulate or repress gene expression depending on the methylation pattern of lysine or arginine residues on histones. These modifications are key factors in mediating the environmental effect on gene expression regulation. Therefore, their aberrant activity is associated with the development of various diseases. The current study aimed to review the significance of DNA and histone methyltransferases and demethylases in developing various conditions, like cardiovascular diseases, myopathies, diabetes, obesity, osteoporosis, cancer, aging, and central nervous system conditions. A better understanding of the epigenetic roles in developing diseases can pave the way for developing novel therapeutic approaches for affected patients.

Evaluation of secretome biomarkers in glioblastoma cancer stem cells: A bioinformatics analysis.

Glioblastoma (GBM) is a malignant brain tumor that frequently occurs alongside other central nervous system (CNS) conditions. The secretome of GBM cells contains a diverse array of proteins released into the extracellular space, influencing the tumor microenvironment. These proteins can serve as potential biomarkers for GBM due to their involvement in key biological processes, exploring the secretome biomarkers in GBM research represents a cutting-edge strategy with significant potential for advancing diagnostic precision, treatment monitoring, and ultimately improving outcomes for patients with this challenging brain cancer. This study was aimed to investigate the roles of secretome biomarkers and their pathwayes in GBM through bioinformatics analysis. Using data from the Gene Expression Omnibus and the Cancer Genome Atlas datasets-where both healthy and cancerous samples were analyzed-we used a quantitative analytical framework to identify differentially expressed genes (DEGs) and cell signaling pathways that might be related to GBM. Then, we performed gene ontology studies and hub protein identifications to estimate the roles of these DEGs after finding disease-gene connection networks and signaling pathways. Using the GEPIA Proportional Hazard Model and the Kaplan-Meier estimator, we widened our analysis to identify the important genes that may play a role in both progression and the survival of patients with GBM. In total, 890 DEGs, including 475 and 415 upregulated and downregulated were identified, respectively. Our results revealed that SQLE, DHCR7, delta-1 phospholipase C (PLCD1), and MINPP1 genes are highly expressed, and the Enolase 2 (ENO2) and hexokinase-1 (HK1) genes are low expressions. Hence, our findings suggest novel mechanisms that affect the occurrence of GBM development, growth, and/or establishment and may also serve as secretory biomarkers for GBM prognosis and possible targets for therapy. So, continued research in this field may uncover new avenues for therapeutic interventions and contribute to the ongoing efforts to combat GBM effectively.

P.014 Intravenous immunoglobulin use for central nervous system disorders in British Columbia: implementation of a provincial screening program

Background: Intravenous Immunoglobulin (IVIg) use for Central Nervous System (CNS) conditions has increased over the last decade. In many CNS disorders, robust evidence for IVIg efficacy is still lacking. Building on the success of the British Columbia (BC) Neuromuscular IVIg utilization initiative, Guidelines for IVIg use in CNS conditions were developed. A provincial screening program was launched in 2023. Methods: For CNS IVIg, requests, diagnosis, dosing, consultation letters and treatment questionnaires were reviewed. Patient management was compared to provincial guidelines. A letter was sent to the ordering physician with the results of the review and treatment recommendations when management differed significantly from guidelines. Review of the first year’s cases was conducted. Results: Over the first 11 months of the program, 79 IVIg renewal requests were reviewed. The most common diagnoses were antibody mediated autoimmune encephalitis, severe drug resistant non-surgical epilepsy and Susac’s syndrome. Recommendations included dose reduction, discontinuation of IVIg, or initiation of alternative therapies for many of the requests. Conclusions: IVIg may be effective in the management of some CNS inflammatory conditions. A physician-led utilization program in BC with targeted education to ordering physicians promotes best practice. Review of year one data will inform a quality improvement cycle to optimize the guidelines.

Paleoneurology of stem palaeognaths clarifies the plesiomorphic condition of the crown bird central nervous system.

Lithornithidae, an assemblage of volant Palaeogene fossil birds, provide our clearest insights into the early evolutionary history of Palaeognathae, the clade that today includes the flightless ratites and volant tinamous. The neotype specimen of Lithornis vulturinus, from the early Eocene (approximately 53 million years ago) of Europe, includes a partial neurocranium that has never been thoroughly investigated. Here, we describe these cranial remains including the nearly complete digital endocasts of the brain and bony labyrinth. The telencephalon of Lithornis is expanded and its optic lobes are ventrally shifted, as is typical for crown birds. The foramen magnum is positioned caudally, rather than flexed ventrally as in some crown birds, with the optic lobes, cerebellum, and foramen magnum shifted further ventrally. The overall brain shape is similar to that of tinamous, the only extant clade of flying palaeognaths, suggesting that several aspects of tinamou neuroanatomy may have been evolutionarily conserved since at least the early Cenozoic. The estimated ratio of the optic lobe's surface area relative to the total brain suggests a diurnal ecology. Lithornis may provide the clearest insights to date into the neuroanatomy of the ancestral crown bird, combining an ancestrally unflexed brain with a caudally oriented connection with the spinal cord, a moderately enlarged telencephalon, and ventrally shifted, enlarged optic lobes.

Pharmacovigilance of carbamazepine in the treatment of Central Nervous System conditions

Anticonvulsants are crucial for treating neurological diseases, necessitating close pharmacovigilance due to their potential risks. For this reason, a prospective descriptive study was conducted to characterize drug-related adverse reactions associated with the use of carbamazepine in the health area of the "Ramon Lopez Peña" Polyclinic, covering the period from July to December 2022. The sample consisted of 35 patients, characterized based on demographic, clinical, and pharmacotherapeutic variables. The detected drug-related adverse events were classified according to causality, severity, and frequency of occurrence. The results showed that the age group of 40-75 years (45.7%) predominated, along with female gender, mixed ethnicity, pre-university education level, and 54.2% did not have any unhealthy habits. The most common diagnosis was epilepsy (68.4%) and among the associated diseases, hypertension was prevalent. The most consumed medications were captopril, hydrochlorothiazide, paracetamol, and metamizole (dipirona). Drug interactions were detected, and 73 adverse reactions occurred, with the nervous system being the most affected at 56.0%. Possible adverse reactions (42.5%), frequent (49.4%), and mild (58.9%) predominated. This study underscores the importance of continuous and effective monitoring in pharmacovigilance to enhance patient safety under carbamazepine treatment, thereby promoting a more rational use of this medication.

The Development of a Regulator of Human Serine Racemase for N-Methyl-D-aspartate Function.

It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.

Cognitive impairment, neuroimaging abnormalities, and their correlations in myotonic dystrophy: a comprehensive review.

Myotonic dystrophy (DM) encompasses a spectrum of neuromuscular diseases characterized by myotonia, muscle weakness, and wasting. Recent research has led to the recognition of DM as a neurological disorder. Cognitive impairment is a central nervous system condition that has been observed in various forms of DM. Neuroimaging studies have increasingly linked DM to alterations in white matter (WM) integrity and highlighted the relationship between cognitive impairment and abnormalities in WM structure. This review aims to summarize investigations into cognitive impairment and brain abnormalities in individuals with DM and to elucidate the correlation between these factors and the potential underlying mechanisms contributing to these abnormalities.

Pathogenetic and pharmacodynamic features of succinic acid derivative application for various diseases of the cardiovascular and nervous systems

This study revealed the pathogenetic patterns of the development of hypoxic and ischemic disorders in various pathological conditions and substantiated approaches to the use of drugs with antihypoxic activity. The role of the receptor interaction of succinic acid in the composition of succinate-containing antihypoxants with succinate receptor SUCNR1 has been demonstrated. The pharmacodynamic properties of the combined preparation of succinic acid that also contains vitamin precursors of the cofactors of Krebs cycle dehydrogenases nicotinamide (precursor of NAD) and riboflavin mononucleotide (precursor of FAD) and precursor of purine nucleotides (inosine) (cytoflavin) for intravenous drip and oral administration were analyzed. Literature data were also analyzed to evaluate the effectiveness of the use of the metabolic corrector of energy-dependent and hypoxic conditions (cytoflavin) in various central nervous system and cardiovascular diseases. In the case of ischemic disorders of cerebral and coronary blood flow, the effects of the drug are concentrated on the penumbra zone (ischemic penumbra), which is associated with the intravenous administration of the drug to its metabolic activity by influencing endothelial cells, restoring microcirculation, and enhancing the oxygen transport function of the blood. Among the new areas of drug use, the use of cytoflavin in the complex therapy of traumatic brain injuries, traumatic shock, acute respiratory distress syndrome, toxic lesions of the central nervous system, multiple organ failure syndrome, and post-COVID syndrome is promising.

Broadening horizons: ferroptosis as a new target for traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc-/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.

Potential injectable hydrogels as biomaterials for central nervous system injury: A narrative review.

Numerous modalities exist through which the central nervous system (CNS) may sustain injury or impairment, encompassing traumatic incidents, stroke occurrences, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Presently available pharmacological and therapeutic interventions are incapable of restoring or regenerating damaged CNS tissue, leading to substantial unmet clinical needs among patients with CNS ailments or injuries. To address and facilitate the recovery of the impaired CNS, cell-based repair strategies encompass multiple mechanisms, such as neuronal replacement, therapeutic factor secretion, and the promotion of host brain plasticity. Despite the progression of cell-based CNS reparation as a therapeutic strategy throughout the years, substantial barriers have impeded its widespread implementation in clinical settings. The integration of cell technologies with advancements in regenerative medicine utilizing biomaterials and tissue engineering has recently facilitated the surmounting of several of these impediments. This comprehensive review presents an overview of distinct CNS conditions necessitating cell reparation, in addition to exploring potential biomaterial methodologies that enhance the efficacy of treating brain injuries.

Terahertz Irradiation Improves Cognitive Impairments and Attenuates Alzheimer’s Neuropathology in the APPSWE/PS1DE9 Mouse: A Novel Therapeutic Intervention for Alzheimer’s Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the deposition of amyloid-β (Aβ), neurofibrillary tangles, neuroinflammation, and neurodegeneration in the brain. In recent years, considering the unsatisfied benefits of pharmacological therapies, non-pharmacological therapy has become a research hotspot for AD intervention. Terahertz (THz) waves with a range between microwave and infrared regions in the electromagnetic spectrum and high permeability to a wide range of materials have great potential in the bioengineering field. However, its biological impacts on the central nervous system, under either physiological or pathological conditions, are poorly investigated. In this study, we first measured the 0.14 THz waves penetration across the skull of a C57BL/6 mouse and found the percentage of THz penetration to be ~70%, guaranteeing that THz waves can reach the relevant brain regions. We then exposed the APPSWE/PS1DE9 mouse model of AD to repeated low-frequency THz waves on the head. We demonstrated that THz waves treatment significantly improved the cognitive impairment and alleviated AD neuropathology including Aβ deposition and tau hyperphosphorylation in the AD mice. Moreover, THz waves treatment effectively attenuated mitochondrial impairment, neuroinflammation, and neuronal loss in the AD mouse brain. Our findings reveal previously unappreciated beneficial effects of THz waves treatment in AD and suggest that THz waves may have the potential to be used as a novel therapeutic intervention for this devastating disease.

Impacts of three different magnetic field applications on M. offininalis seed germination and seedling growth

The herb Melissa officinalis L., most commonly recognized as lemon balm, has been used as a treatment for problems with the brain and central nervous system, headaches, nervousness, digestive disorders, respiratory and circulatory conditions, various types of cancer and rheumatism. This investigation was designated to compare the impacts of 3 discrete magnetic field strengths (50 mT, 100 mT and 150 mT) with various time periods of exposure (5 min, 15 min, 30 min, 1 hr and 3 hr) on M. officinalis seed germination (rate and onset) and seedling growth (length of shoot-root, weight of fresh-dry and water content). The seeds, which were surface sterilized in petri plates, were subjected to different applications, including exposure to various magnetic fields and control (without exposure). Germination was assessed by observing the radicular protrusion. The number of germinated seeds was recorded over 20 days. In all 3 magnetic field applications, exposure to magnetic field for 1 hr caused the highest number of seed germination (36%, 52% and 50% for 50 mT, 100 mT and 150 mT, respectively) comparing to control (28%). The onset of seed germination was earlier with magnetic field application (day 7) compared to control (day 11). Growth elements and water contents of the seedling were assessed in order to understand the impact of different magnetic field applications. Implementation of 100 mT and 150 mT magnetic field for 1 hr increased shoot and root length in addition to fresh weight of the seedlings. The maximum dry weight increase was provided by 150 mT-5 min, 15 min and 30 min. The highest water content (%) was observed with exposure to 150 mT (68%) and 100 mT (66%) for 1 hr compared to control (44%). Magnetic field intensity of 100 mT and 150 mT for 1 hr was the most efficient in the seed germination and seedling growth.

Pegylated Nanoparticles for Brain Targeting- Opportunities and Challenges

Abstract: As the blood-brain barrier (BBB) stops hazardous substances from entering the brain, creating treatment strategies to treat central nervous system (CNS) conditions is difficult. By circumventing the BBB, nanotechnology has emerged as a viable method for targeted medicine delivery to the brain. PEGylated nanoparticles (PEGNPs) have shown the ability to encapsulate a range of drugs and deliver them to the deepest regions of the brain. PEGNPs are a helpful tool in preclinical research for CNS diseases because of their extreme flexibility. Before PEGNPs can be employed in clinical practise, however, issues with their design and optimization for efficient brain targeting, as well as their long-term safety, must be resolved. Moreover, it is crucial to comprehend the basic principles of PEGNP trafficking through the BBB and how they affect CNS cells. Despite these difficulties, PEGNPs have the potential to completely alter the way CNS diseases are treated by allow-ing for precise medication delivery to the brain. This review emphasizes the potential and difficul-ties in using PEGNPs for brain targeting and describes current breakthroughs in PEGNP research for CNS diseases.