Central Nervous System Conditions Research Articles

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.

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.

Viral Meningitis and Encephalitis Update

Abstract Purpose of Review This review describes advances in the diagnosis, treatment, and prevention of non-bacterial meningitis and encephalitis, with a focus on emerging viral causes of central nervous system (CNS) infection. Recent Findings The Infectious Diseases Society of America recently published new guidelines for the management of encephalitis. Multiple articles have been published detailing emerging etiologies in human CNS infections, including analyses of neurological complications in the ongoing COVID-19 pandemic. Finally, several novel viral detection methods have been described, which may improve the detection of the specific etiologies of CNS infections (Hongyan et al. Front Neurol 14, [1]). Summary Meningitis and encephalitis remain important causes of morbidity and mortality. They are as a whole uncommon, yet timely diagnosis, treatment, and disposition are still critical to improve patient outcomes. In clinical practice the exact cause of encephalitis is frequently unidentified, making supportive care often the only available treatment. Emergency physicians, neurologists, infectious disease doctors, and intensive care unit specialists will benefit from reviewing this discussion on emerging pathogens, as well as from reviewing advances in virology, immunology, and the imaging of inflammatory CNS conditions.

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.

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 (GSK3β), 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.

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

AbstractAlzheimer'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.

Central Nervous System-related Conditions and Associated Healthcare Resource Use Among Japanese nmCRPC Patients Based on Retrospective Claims Data.

Background: Japanese patients with prostate cancer are typically treated with primary androgen deprivation therapy (ADT), most commonly administered as a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen (AA). Since LHRH agonists and AA therapy can be maintained for several years, the long-term effects of these treatments on patients must be carefully considered, including the risk of concomitant central nervous system (CNS) conditions which could affect treatment choices. Objective: To describe CNS-related concomitant conditions during ADT and/or AA treatment and the subsequent healthcare resource utilization in Japanese nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. Methods: Patients diagnosed with nmCRPC and CNS-related conditions while on ADT and/or AA therapy between April 2009 and August 2017 were retrospectively followed up for a maximum of 2 years using a claims database. Results: A total of 455 patients (average age, 78.5 years), were included. The 3 most common concomitant CNS-related conditions were pain (~60% of events), insomnia (~30%), and headache (2%-3%). The frequency of CNS-related conditions in these patients increased approximately threefold after starting AA therapy (before, 969 events; after, 2802). On average, a patient had 10 episodes of concomitant CNS-related conditions in a year. Medical costs did not significantly increase due to CNS-related conditions. Discussion: The most frequently reported CNS-related conditions were pain, insomnia, and headaches. Furthermore, more concomitant CNS-related conditions 1 year after CRPC diagnosis and 1 year after starting AA treatment were recorded. Conclusion: Patients with nmCRPC experience an increase in the frequency of concomitant CNS-related conditions, including pain, insomnia, and headaches, after CRPC diagnosis or starting AA treatment. Future research should explore the causes of this increased frequency.

Central Nervous System-related Conditions and Associated Healthcare Resource Use Among Japanese nmCRPC Patients Based on Retrospective Claims Data

Background: Japanese patients with prostate cancer are typically treated with primary androgen deprivation therapy (ADT), most commonly administered as a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen (AA). Since LHRH agonists and AA therapy can be maintained for several years, the long-term effects of these treatments on patients must be carefully considered, including the risk of concomitant central nervous system (CNS) conditions which could affect treatment choices. Objective: To describe CNS-related concomitant conditions during ADT and/or AA treatment and the subsequent healthcare resource utilization in Japanese nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. Methods: Patients diagnosed with nmCRPC and CNS-related conditions while on ADT and/or AA therapy between April 2009 and August 2017 were retrospectively followed up for a maximum of 2 years using a claims database. Results: A total of 455 patients (average age, 78.5 years), were included. The 3 most common concomitant CNS-related conditions were pain (~60% of events), insomnia (~30%), and headache (2%-3%). The frequency of CNS-related conditions in these patients increased approximately threefold after starting AA therapy (before, 969 events; after, 2802). On average, a patient had 10 episodes of concomitant CNS-related conditions in a year. Medical costs did not significantly increase due to CNS-related conditions. Discussion: The most frequently reported CNS-related conditions were pain, insomnia, and headaches. Furthermore, more concomitant CNS-related conditions 1 year after CRPC diagnosis and 1 year after starting AA treatment were recorded. Conclusion: Patients with nmCRPC experience an increase in the frequency of concomitant CNS-related conditions, including pain, insomnia, and headaches, after CRPC diagnosis or starting AA treatment. Future research should explore the causes of this increased frequency.

Transplantation of MiR-28-5p-Modified BMSCs Promotes Functional Recovery After Spinal Cord Injury

Traumatic spinal cord injury (TSCI) is a prevalent central nervous system condition that imposes a significant burden on both families and society, affecting more than 2 million people worldwide. Recently, there has been increasing interest in bone marrow mesenchymal stem cell (BMSC) transplantation as a promising treatment for spinal cord injury (SCI) due to their accessibility and low immunogenicity. However, the mere transplantation of BMSCs has limited capacity to directly participate in the repair of host spinal cord nerve function. MiR-28-5p, identified as a key differentially expressed miRNA in spinal cord ischemia–reperfusion injury, exhibits differential expression and regulation in various neurological diseases. Nevertheless, its involvement in this process and its specific regulatory mechanisms in SCI remain unclear. Therefore, this study aimed to investigate the potential mechanisms through which miR-28-5p promotes the neuronal differentiation of BMSCs both in vivo and in vitro. Our results indicate that miR-28-5p may directly target Notch1, thereby facilitating the neuronal differentiation of BMSCs in vitro. Furthermore, the transplantation of lentivirus-mediated miR-28-5p-overexpressed BMSCs into SCI rats effectively improved footprint tests and Basso, Beattie, and Bresnahan (BBB) scores, ameliorated histological morphology (hematoxylin–eosin [HE] and Nissl staining), promoted axonal regeneration (MAP2 and growth-associated protein 43 [GAP43]), and facilitated axonal remyelination (myelin basic protein [MBP]). These findings may suggest that miR-28-5p-modified BMSCs could serve as a therapeutic target to enhance the behavioral and neurological recovery of SCI rats.

CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation.

Chitinase-3-like protein 1 (CHI3L1) is primarily secreted by activated astrocytes in the brain and is known as a reliable biomarker for inflammatory central nervous system (CNS) conditions such as neurodegeneration and autoimmune disorders like neuromyelitis optica (NMO). NMO is an astrocyte disease caused by autoantibodies targeting the astroglial protein aquaporin 4 (AQP4) and leads to vision loss, motor deficits, and cognitive decline. In this study examining CHI3L1's biological function in neuroinflammation, we found that CHI3L1 expression correlates with cognitive impairment in our NMO patient cohort. Activated astrocytes secrete CHI3L1 in response to AQP4 autoantibodies, and this inhibits the proliferation and neuronal differentiation of neural stem cells. Mouse models showed decreased hippocampal neurogenesis and impaired learning behaviors, which could be rescued by depleting CHI3L1 in astrocytes. The molecular mechanism involves CHI3L1 engaging the CRTH2 receptor and dampening β-catenin signaling for neurogenesis. Blocking this CHI3L1/CRTH2/β-catenin cascade restores neurogenesis and improves cognitive deficits, suggesting the potential for therapeutic development in neuroinflammatory disorders.

The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases.

Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and other CNS conditions. Despite substantial progress in understanding and treating the underlying pathological processes in various neurological diseases, there is still a notable absence of effective therapeutic approaches aimed specifically at mitigating the damage caused by these illnesses. Remarkably, ischemia causes severe damage to cells in ischemia-associated CNS diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including mitochondrial permeability transition pore (MPTP) opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of ischemia-associated CNS diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in cerebral ischemia have not yet been clarified. Thus, we analyzed the underlying mechanism between mitochondrial dysfunction and ferroptosis in ischemia-associated CNS diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of ROS and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of ischemia-associated CNS diseases.

Prevalence of dementia and its association with central nervous system infections among older persons in northern Uganda: cross-sectional community-based study

BackgroundDementia is a condition in which there is deterioration in cognitive function beyond what might be expected from the usual consequence of biological aging. Few studies have been conducted on the prevalence of dementia and its association with central nervous system (CNS) infections among older persons in African settings, particularly in Uganda. Therefore, this study assessed the prevalence of dementia and its association with CNS infections among older persons in Lira District, northern Uganda.MethodsThis was a cross-sectional community-based study in Lira district northern Uganda. The study was conducted in March 2022 among 434 older persons aged 50 and above years who were selected by multistage sampling. Data were collected using an interviewer-administered questionnaire supplemented with information from participant’s medical records and a brief community screening instrument for dementia. The instrument classifies dementia into unlikely, probable or possible dementia. Data were entered in duplicate into EpiData version 3.0, then transferred to Statistical Package for Social Sciences (SPSS) version 23 for statistical analysis.ResultsOur study found almost one in four (23%) of the older persons in Lira district northern Uganda were suffering from probable or possible dementia. Our study further found that older persons in Lira district northern Uganda with a positive history of central nervous system infections (CNS) had nearly five times higher odds of having probable or possible dementia compared to their counterparts (cOR: 4.5; 2.76–7.23; p ≤ 0.001). Being in advanced age of 70 + years (aOR: 2.6; 1.6–4.3; p ≤ 0.001), positive history of CNS infection particularly Herpes simplex virus-1 (aOR: 5.4; 1.4–20.5; p = 0.013), and chronic headache (aOR: 1.9; 1.1–3.1; p = 0.019) were independent predictors of probable or possible dementia among participants in this study.Conclusion and recommendationsDementia is a common condition among older persons in Lira district northern Uganda with a prevalence of 23% in our study. Older persons with a positive history of CNS infection had higher odd of developing dementia compared to their counterparts. Having advanced age, cerebral malaria, Herpes simplex virus − 1 (HSV-1) infections, and chronic headache were independent predictors for dementia. These results imply that health assessment for the risk of dementia should include screening for history of CNS conditions particularly cerebral malaria, HSV-1 and chronic headache.

Histopathological changes of the dural myeloid cells and lymphatic vessels in a mouse model of sepsis-associated encephalopathy

As a common diffuse encephalopathy caused by sepsis, sepsis-associated encephalopathy (SAE) is closely associated with increased mortality, severe cognition dysfunction and increased cost of health care in patients of sepsis. Accumulating evidence suggests that the dura mater, the outermost meninges of the central nervous system (CNS), plays an important role in CNS immunity, especially with the discovery of meningeal lymphatic vessels (mLVs), as well as a plentiful array of resident or infiltrating immune cells harbored in the dura. Although these findings have significantly enhanced our understanding of the immune function of dura under both steady-state and pathological condition of CNS, whether and how the immune cells and mLVs within dura response to SAE still remains largely unexplored. Here, we established lipopolysaccharide (LPS) intraperitoneal injection-induced SAE model and examined the dural resident immune cells and mLVs. We analysed the histological change in dura by performing hematoxylin and eosin (H&E) and immunofluorescence staining. Results showed that systemic exposure to LPS induced neutrophils recruitment, exudation and gathering around the dural blood vessels. Moreover, resident macrophage altered its shape as well as location, and downregulated major histocompatibility (MHC) class II expression following LPS injection. We also found that LPS exposure induced dorsal meningeal lymphangiogenesis. Together, these findings collectively demonstrated that LPS-induced SAE can stimulate immune cells and mLVs within dura and provided more information about the immune response of the dura in sepsis.

Nucleic acid-based therapeutics for the treatment of central nervous system disorders.

Nucleic acid-based therapeutics (NBTs) are an emerging class of drugs with potential for the treatment of a wide range of central nervous system conditions. To date, pertaining to CNS indications, there are two commercially available NBTs and a large number of ongoing clinical trials. However, these NBTs are applied directly to the brain due to very low blood brain barrier permeability. In this review, we outline recent advances in chemical modifications of NBTs and NBT delivery techniques intended to promote brain exposure, efficacy, and possible future systemic application.