Central Nervous System Damage Research Articles

Contrasting the brain imaging features of MOG-antibody disease, with AQP4-antibody NMOSD and multiple sclerosis

Background: Identifying magnetic resonance imaging (MRI) markers in myelin-oligodendrocytes-glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder-aquaporin-4 positive (NMOSD-AQP4) and multiple sclerosis (MS) is essential for establishing objective outcome measures. Objectives: To quantify imaging patterns of central nervous system (CNS) damage in MOGAD during the remission stage, and to compare it with NMOSD-AQP4 and MS. Methods: 20 MOGAD, 19 NMOSD-AQP4, 18 MS in remission with brain or spinal cord involvement and 18 healthy controls (HC) were recruited. Volumetrics, lesions and cortical lesions, diffusion-imaging measures, were analysed. Results: Deep grey matter volumes were lower in MOGAD (p = 0.02) and MS (p = 0.0001), compared to HC and were strongly correlated with current lesion volume (MOGAD R = −0.93, p < 0.001, MS R = −0.65, p = 0.0034). Cortical/juxtacortical lesions were seen in a minority of MOGAD, in a majority of MS and in none of NMOSD-AQP4. Non-lesional tissue fractional anisotropy (FA) was only reduced in MS (p = 0.01), although focal reductions were noted in NMOSD-AQP4, reflecting mainly optic nerve and corticospinal tract pathways. Conclusion: MOGAD patients are left with grey matter damage, and this may be related to persistent white matter lesions. NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes, but reduced non-lesional tissue FA. Observations from our study can be used to identify new markers of damage for future multicentre studies.

Development of immunofluorescent diagnostics for the determination of IgM and IgG antibodies to herpes simplex virus types 1 and 2.

The Russian kits «HSV-1-Fluorogen-screen» and «HSV-2-Fluorogen-screen» have been developed for the determination of antibodies M and G to herpes simplex virus types 1 and 2 by the immunofluorescence reaction. The kits were used to examine the positive and negative standard «EKOlab» panels sera and showed 100% sensitivity and specificity of the developed tests. 125 samples of blood serum from people with clinical diagnoses such as herpetic, cytomegalovirus infections, pyelonephritis, conjunctivitis and central nervous system damage were tested in parallel with using the enzyme-linked immunosorbent assay systems from different manufacturers and the developed tests «HSV-1-Fluorogen-screen» and «HSV-2-Fluorogen-screen». A high degree of matching of results with comparison sets was observed in examined samples. The developed diagnostics can be successfully used in clinical practice both for screening and for verification of results of the diagnosis of herpesvirus infections caused by herpes simplex virus types 1 and 2.

Intranasally Administered L-Myc-Immortalized Human Neural Stem Cells Migrate to Primary and Distal Sites of Damage after Cortical Impact and Enhance Spatial Learning.

As the success of stem cell-based therapies is contingent on efficient cell delivery to damaged areas, neural stem cells (NSCs) have promising therapeutic potential because they inherently migrate to sites of central nervous system (CNS) damage. To explore the possibility of NSC-based therapy after traumatic brain injury (TBI), isoflurane-anesthetized adult male rats received a controlled cortical impact (CCI) of moderate severity (2.8 mm deformation at 4 m/s) or sham injury (i.e., no cortical impact). Beginning 1-week post-injury, the rats were immunosuppressed and 1 × 106 human NSCs (LM-NS008.GFP.fLuc) or vehicle (VEH) (2% human serum albumen) were administered intranasally (IN) on post-operative days 7, 9, 11, 13, 15, and 17. To evaluate the spatial distributions of the LM-NSC008 cells, half of the rats were euthanized on day 25, one day after completion of the cognitive task, and the other half were euthanized on day 46. 1 mm thick brain sections were optically cleared (CLARITY), and volumes were imaged by confocal microscopy. In addition, LM-NSC008 cell migration to the TBI site by immunohistochemistry for human-specific Nestin was observed at day 39. Acquisition of spatial learning was assessed in a well-established Morris water maze task on six successive days beginning on post-injury day 18. IN administration of LM-NSC008 cells after TBI (TBI + NSC) significantly facilitated spatial learning relative to TBI + VEH rats (p < 0.05) and had no effect on sham + NSC rats. Overall, these data indicate that IN-administered LM-NSC008 cells migrate to sites of TBI damage and that their presence correlates with cognitive improvement. Future studies will expand on these preliminary findings by evaluating other LM-NSC008 cell dosing paradigms and evaluating mechanisms by which LM-NSC008 cells contribute to cognitive recovery.

Brain organoids: A promising model to assess oxidative stress-induced central nervous system damage.

Oxidative stress (OS) is one of the most significant propagators of systemic damage with implications for widespread pathologies such as vascular disease, accelerated aging, degenerative disease, inflammation, and traumatic injury. OS can be induced by numerous factors such as environmental conditions, lifestyle choices, disease states, and genetic susceptibility. It is tied to the accumulation of free radicals, mitochondrial dysfunction, and insufficient antioxidant protection, which leads to cell aging and tissue degeneration over time. Unregulated systemic increase in reactive species, which contain harmful free radicals, can lead to diverse tissue-specific OS responses and disease. Studies of OS in the brain, for example, have demonstrated how this state contributes to neurodegeneration and altered neural plasticity. As the worldwide life expectancy has increased over the last few decades, the prevalence of OS-related diseases resulting from age-associated progressive tissue degeneration. Unfortunately, vital translational research studies designed to identify and target disease biomarkers in human patients have been impeded by many factors (e.g., limited access to human brain tissue for research purposes and poor translation of experimental models). In recent years, stem cell-derived three-dimensional tissue cultures known as "brain organoids" have taken the spotlight as a novel model for studying central nervous system (CNS) diseases. In this review, we discuss the potential of brain organoids to model the responses of human neural cells to OS, noting current and prospective limitations. Overall, brain organoids show promise as an innovative translational model to study CNS susceptibility to OS and elucidate the pathophysiology of the aging brain.

Flavonoids modulate AMPK/PGC-1α and interconnected pathways toward potential neuroprotective activities.

As progressive, chronic, incurable and common reasons for disability and death, neurodegenerative diseases (NDDs) are significant threats to human health. Besides, the increasing prevalence of neuronal gradual degeneration and death during NDDs has made them a global concern. Since yet, no effective treatment has been developed to combat multiple dysregulated pathways/mediators and related complications in NDDs. Therefore, there is an urgent need to create influential and multi-target factors to combat neuronal damages. Accordingly, the plant kingdom has drawn a bright future. Among natural entities, flavonoids are considered a rich source of drug discovery and development with potential biological and medicinal activities. Growing studies have reported multiple dysregulated pathways in NDDs, which among those mediator AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) play critical roles. In this line, critical role of flavonoids in the upregulation of AMPK/PGC-1α pathway seems to pave the road in the treatment of Alzheimer's disease (AD), Parkinson's disease (PD), aging, central nervous system (brain/spinal cord) damages, stroke, and other NDDs. In the present study, the regulatory role of flavonoids in managing various NDDs has been shown to pass through AMPK/PGC-1α signaling pathway.

Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions

Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson’s disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

Advanced oxidation processes for chlorpyrifos removal from aqueous solution: a systematic review.

Chlorpyrifos (CPF), an organophosphate insecticide, due to its high efficiency and low cost is widely used in the agricultural industry. CPF may lead to lung deficiency, central nervous system damage, developmental and autoimmune disorders. In recent decades, the advanced oxidation processes (AOPs) have been considered in water and wastewater treatment due to their high efficiency in decomposition of organic and inorganic compounds, specially hardly biodegradable or non-biodegradable compounds. In the present review study, the most common AOPs (such as Fenton and Photo-Fenton processes, UV/H2O2 photolysis, UV/TiO2 heterogeneous photo catalysis, electrochemical processes, sonolysis technology, gamma irradiation technology and sulfate-based AOPs) applied for CPF removal from aqueous matrices has been investigated. It can be concluded that the use of AOPs are effective for CPF removal from aqueous media. In addition, Fenton and photocatalytic processes appear to be the most common techniques for CPF degradation.

The furin-S2' site in avian coronavirus plays a key role in central nervous system damage progression.

The furin cleavage site plays an important role in virus pathogenicity. The spike protein of SARS-CoV-2 harbors a furin cleavage site insertion in contrast to SARS-CoV, which may be related to its stronger communicability. An avian coronavirus with an extra furin cleavage site upstream of the fusion peptide (S2' site) infected monocyte cells and neuron cells leading to viremia or encephalitis, respectively. Immunohistochemistry and real-time quantitative polymerase chain reaction were used to follow disease progression and demonstrated differences between the parent avian coronavirus and mutated avian coronavirus with a furin-S2' site. Magnetic resonance imaging and biological dye to evaluate the blood-brain barrier permeability showed that avian coronavirus with a furin-S2' site had increased permeability compared with parent avian coronavirus. Immunohistochemistry of brains after intracerebral injection of avian coronavirus and immunofluorescence staining of primary neuron cells demonstrated the furin-S2' site expanded the cell tropism of the mutant avian coronavirus to neuron cells. TNF-α, which has a key role in blood-brain barrier permeability, was highly induced by avian coronavirus with a furin-S2' site compared with the parent avian coronavirus. We demonstrated the process involved in mutant avian coronavirus-induced disease and that the addition of a furin-S2' site changed the virus cell tropism.IMPORTANCECoronaviruses have broken out three times in two decades. Spike (S) protein plays a key role in the process of infection. To clarify importance of furin cleavage site in spike protein for coronavirus, we investigated the pathogenesis of neurotropic avian coronavirus whose spike protein contains an extra furin cleavage site (furin-S2' site). By combining real-time quantitative polymerase chain reaction and immunohistochemistry we demonstrated that infectious bronchitis virus (IBV) infects brain instead of trachea when its S protein contains furin-S2' site. Moreover, the virus was shown to increase the permeability of blood-brain barrier, infect neuron cells and induce high expression of TNF-α. Based on these results we further show that furin cleavage site in S protein plays an important role in coronavirus pathogenicity and cell tropism. Our study extends previous publications on function of S protein of coronavirus, increasing the understanding of researchers to coronavirus.

Construction of the recombinant Escherichia coli strain producing a homologous thermolabile toxin subunit

Colibacteriosis is an acute zoonotic disease manifested by septicaemia, toxemia, enteritis, body dehydration, and central nervous system damage. Depending on the presence of virulence factors and the nature of interaction with the intestinal mucosa, enterotoxigenic, enteroinvasive, enteropathogenic, and enterohemorrhagic E. coli are isolated. Enterotoxigenic strains of E. coli occupy one of the leading places in the etiological structure of calf colibacteriosis in many livestock farms of the Republic of Belarus. The main reason why this disease develops is the presence of thermolabile and thermostable toxins in the causative strain. The thermolabile toxin subunit B is a potent antigen that allows pet immunity to be acquired against E. coli-induced cattle diarrhea. Many foreign vaccines used against intestinal infections of cattle contain either a native or recombinant variant of the subunit B. As a result of the work, we have created a new strain of E. coli 42eLTB – the producer of the recombinant subunit B of the thermolabile toxin E. coli. The producing capacity of the obtained strain is 480 mg with 1 culture liquid liter, which exceeds the already known strains 1.37 times.

One Raft to Guide Them All, and in Axon Regeneration Inhibit Them.

Central nervous system damage caused by traumatic injuries, iatrogenicity due to surgical interventions, stroke and neurodegenerative diseases is one of the most prevalent reasons for physical disability worldwide. During development, axons must elongate from the neuronal cell body to contact their precise target cell and establish functional connections. However, the capacity of the adult nervous system to restore its functionality after injury is limited. Given the inefficacy of the nervous system to heal and regenerate after damage, new therapies are under investigation to enhance axonal regeneration. Axon guidance cues and receptors, as well as the molecular machinery activated after nervous system damage, are organized into lipid raft microdomains, a term typically used to describe nanoscale membrane domains enriched in cholesterol and glycosphingolipids that act as signaling platforms for certain transmembrane proteins. Here, we systematically review the most recent findings that link the stability of lipid rafts and their composition with the capacity of axons to regenerate and rebuild functional neural circuits after damage.

PKU and COVID19: How the pandemic changed metabolic control

BackgroundCOVID19 pandemic urged the need to take severe measures for reducing the epidemic spread. Lockdowns were imposed throughout countries and even Inborn errors of metabolism (IEMs) affected patients had to face it and adapt, with management strategies changes coming along. Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism causing, when not treated, blood Phe increases and consequent central nervous system (CNS) damage. Dietary intervention is the main recognized treatment and must be maintained long-life, however adherence is often suboptimal in adulthood. Aim of this study was to evaluate whether and how the pandemic had impacted PKUs metabolic control and what factors may have played a role as potential modifiers. MethodsPatients ≥4 yo and in follow-up at our Metabolic Clinic were enrolled in this study, divided into subgroups according to age (GROUP A < 12 yo; GROUP B ≥ 12 yo). Videoconsults were conducted on a minimum monthly basis and collected DBS were studied and compared to previous year same time-period in order to evaluate possible changes. Results39% of patients (n = 121) increased the number of performed DBS. “Non-compliant” patients were reduced (11–3%) with a − 14% of patients with mean Phe levels >600 umol/l and a − 8% of patients with 100% DBS above same level. GROUP A maintained substantially unchanged metabolic control among two analyzed time-periods. On the contrary, GROUP B demonstrated significant reductions in mean blood Phe concentrations (p < 0.0001) during the pandemic (mean 454 umol/l, SD ± 252, vs. 556.4 umol/l, SD ± 301). DiscussionCOVID19 pandemic strongly impacted people's life with lifestyle habits changing consistently. PKU patients had to adapt their dietary restrictions to the new environment they were exposed to and, if younger patients could have been less exposed (meals strictly according to diet plan independently from setting), adolescent and adults strongly reflected the obligation to stay home by showing better metabolic control. Multiple factors could have played a role in that and the availability of teleconsultancy may have contributed allowing easier connections, but our data demonstrate how the pandemic and the environment can strongly impact PKUs adherence to treatment and how removing distance barriers can ameliorate and optimize metabolic compliance.

Conversion Disorder and Spinal cord Injury: Case report

Introduction: The aetiology of conversion disorder is unknown, though association with emotional stress and with organic brain disorder has been described. Paraplegia as a conversion reaction has been reported infrequently. Combination of motor and sensory disturbance, other than paraplegia, may occur as a manifestation of a conversion reaction, and may suggest Spinal Cord Injury (SCI). Case Report: A 35-year-old Italian woman who had a history of post traumatic SCI which affected her lower limb when she was 29 years old. Patient was unable to empty his bladder completely.The aim of this paper is to describe the correlation between diagnosis of conversion disease and SCI. Clinical Rehabilitation Impact: Chronic conversion disorder can be resistant to rehabilitation treatment. Neurophysiological diagnostic procedures adopted in our study discern the degree of central and peripheral nervous system damage and confirmed the integrity of spinal cord in conversion disorder. Conclusion: Our case report describes the association between conversion disease, SCI, and neurophysiological tests and suggests to apply the neurophysiological tests to validate conversion disorder diagnosis in SCI.

Urban air pollution induces alterations in redox metabolism and mitochondrial dysfunction in mice brain cortex

Previous reports indicate that the central nervous system (CNS) is a target of air pollution, causing tissue damage and functional alterations. Oxidative stress and neuroinflammation have been pointed out as possible mechanisms mediating these effects. The aim of this work was to study the chronic effects of urban air pollution on mice brain cortex, focusing on oxidative stress markers, and mitochondrial function. Male 8-week-old BALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside whole-body exposure chambers, located in a highly polluted area of Buenos Aires city, for up to 4 weeks. Glutathione levels, assessed as GSH/GSSG ratio, were decreased after 1 and 2 weeks of exposure to UA (45% and 25% respectively vs. FA; p < 0.05). A 38% increase in lipid peroxidation was found after 1 week of UA exposure (p < 0.05). Regarding protein oxidation, carbonyl content was significantly increased at week 2 in UA-exposed mice, compared to FA-group, and an even higher increment was found after 4 weeks of exposure (week 2: 40% p < 0.05, week 4: 54% p < 0.001). NADPH oxidase (NOX) and glutathione peroxidase (GPx) activities were augmented at all the studied time points, while superoxide dismutase (Cu,Zn-SOD cytosolic isoform) and glutathione reductase (GR) activities were increased only after 4 weeks of UA exposure (p < 0.05). The increased NOX activity was accompanied with higher expression levels of NOX2 regulatory subunit p47phox, and NOX4 (p < 0.05). Also, UA mice showed impaired mitochondrial function due to a 50% reduction in O2 consumption in active state respiration (p < 0.05), a 29% decrease in mitochondrial inner membrane potential (p < 0.05), a 65% decrease in ATP production rate (p < 0.01) and a 30% increase in H2O2 production (p < 0.01). Moreover, respiratory complexes I-III and II-III activities were decreased in UA group (30% and 36% respectively vs. FA; p < 0.05). UA exposed mice showed alterations in mitochondrial function, increased oxidant production evidenced by NOX activation, macromolecules damage and the onset of the enzymatic antioxidant system. These data indicate that oxidative stress and impaired mitochondrial function may play a key role in CNS damage mechanisms triggered by air pollution.

Nutritional support for patients in the neurosurgical and neurological intensive care unit: are special guidelines necessary?

The nutritional support for patients in the intensive care unit is an integral component of intensive care. Patients of a neurological and neurosurgical profile who are in the intensive care unit are a special group of patients, whose treatment differs both in the used intensive therapy methods and nutritional support provision.&#x0D; Indirect calorimetry should be used to determine the energy requirements in neurosurgical and neurological patients. The use of calculation equations, such as the Harris-Benedict equation, is impossible due to its large discrepancy with indirect calorimetry data. The need for protein in patients of this category should be made at the rate of 1.22.0 g/kg of body weight per day. The urinary nitrogen loss data should not be used as a routine method for determining protein requirements in these patients. Insufficient energy and protein intake in neurosurgical and neurological patients can lead to increased infectious complications, mechanical ventilation duration, and length of intensive care unit stay, and rehabilitation potential deterioration. Excessive energy intake can lead to increased carbon dioxide production and intra-abdominal pressure, thereby increasing the intracranial pressure and aggravating secondary brain damage.&#x0D; The central nervous system damage leads to increased intestinal permeability, worsens motility, and even changes the microbiota, which requires constant monitoring of the gastrointestinal tract functions to provide adequate nutritional support in neurological and neurosurgical patients who are in the intensive care unit.&#x0D; In modern guidelines, both on intensive care and nutritional support, recommendations for its implementation in these patients are unclear.

SARS-CoV-2 Spike Targets USP33-IRF9 Axis via Exosomal miR-148a to Activate Human Microglia.

SARS-CoV-2, the novel coronavirus infection has consistently shown an association with neurological anomalies in patients, in addition to its usual respiratory distress syndrome. Multi-organ dysfunctions including neurological sequelae during COVID-19 persist even after declining viral load. We propose that SARS-CoV-2 gene product, Spike, is able to modify the host exosomal cargo, which gets transported to distant uninfected tissues and organs and can initiate a catastrophic immune cascade within Central Nervous System (CNS). SARS-CoV-2 Spike transfected cells release a significant amount of exosomes loaded with microRNAs such as miR-148a and miR-590. microRNAs gets internalized by human microglia and suppress target gene expression of USP33 (Ubiquitin Specific peptidase 33) and downstream IRF9 levels. Cellular levels of USP33 regulate the turnover time of IRF9 via deubiquitylation. Our results also demonstrate that absorption of modified exosomes effectively regulate the major pro-inflammatory gene expression profile of TNFα, NF-κB and IFN-β. These results uncover a bystander pathway of SARS-CoV-2 mediated CNS damage through hyperactivation of human microglia. Our results also attempt to explain the extra-pulmonary dysfunctions observed in COVID-19 cases when active replication of virus is not supported. Since Spike gene and mRNAs have been extensively picked up for vaccine development; the knowledge of host immune response against spike gene and protein holds a great significance. Our study therefore provides novel and relevant insights regarding the impact of Spike gene on shuttling of host microRNAs via exosomes to trigger the neuroinflammation.

Danhong Injection Attenuates Cerebral Ischemia-Reperfusion Injury in Rats Through the Suppression of the Neuroinflammation.

Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1β, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.

Design and Implementation ofReal-time Electrical Stimulation Artifact Suppression based on STM32

A biosignal is used as a control signal for electrical stimulation to restore weakened muscle function due to damage to the central nervous system. In patients with central nervous system damage, sufficient muscle contraction does not occur spontaneously. In this case, applying electrical stimulation can cause normal muscle contraction. However, it is necessary to remove the electrical stimulation artifact caused by the electrical stimulation. This paper describes a system design that removes electrical stimulation artifact in real time using a Cortex-M4-based STM32F processor. The STM32F is a very advantageous MCU for such DSPs, especially because it has a built-in floating point operator. Using STM32F's various high-performance peripherals (12-bit parallel ADC and 12-bit DAC, UART, Timer), an optimized embedded system was implemented.In this paper, the simulated and real-time results were compared and evaluated with the designed fir filter. In addition, the performance of the filter was evaluated through frequency analysis. As a result, it was verified that a high-performance 32-bit STM32F with floating point calculator and various peripherals is suitable for real-time signal processing

Transneuronal Degeneration in the Brain During Glaucoma.

The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains unclear. RGCs are a group of central nervous system (CNS) neurons whose soma are in the inner retina. The axons of RGCs form the optic nerve and converge at the optic chiasma; from there, they project to the visual cortex via the lateral geniculate nucleus (LGN). In recent years, there has been increasing interest in the dysfunction and death of CNS and retinal neurons caused by transneuronal degeneration of RGCs, and the view that glaucoma is a widespread neurodegenerative disease involving CNS damage appears more and more frequently in the literature. In this review, we summarize the current knowledge of LGN and visual cortex neuron damage in glaucoma and possible mechanisms behind the damage. This review presents an updated and expanded view of neuronal damage in glaucoma, and reveals new and potential targets for neuroprotection and treatment.

Potential Application of Vaporized Drugs via Nasal Inhalers to Prevent Mortality and Central Nervous System Damage Caused by Primary Amoebic Meningoencephalitis Due to Naegleria fowleri

Here, it is proposed that nasal inhalers with specific anti-Naegleria fowleri drugs or a combination of anti-N. fowleri compounds combined with steroids such as dexamethasone could provide a practical solution for treating primary amoebic meningoencephalitis.

Systematic Review - Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta-analysis.

To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify experimental studies comparing the mitigating effect of ketosis (intervention) versus non-ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary endpoints were a reduction in neuronal damage and dysfunction, and an 'aggregated advantage' (composite of all primary and secondary endpoints). Hedges' g was the effect measure. Subgroup analyses evaluated the modulatory effect of age, insult type, and injury site. Meta-regression evaluated timing, type, and magnitude of intervention as predictors of neuroprotection. The selected publications were 49 experimental murine studies (period 1979-2020). The intervention reduced mortality (g 2.45, SE 0.48, p<.01), neuronal damage (g 1.96, SE 0.23, p<.01) and dysfunction (g 0.99, SE 0.10, p<.01). Reduction of mortality was particularly pronounced in the adult subgroup (g 2.71, SE 0.57, p<.01). The aggregated advantage of ketosis was stronger in the pediatric (g 3.98, SE 0.71, p<.01), brain (g 1.96, SE 0.18, p<.01), and ischemic insult (g 2.20, SE 0.23, p<.01) subgroups. Only the magnitude of intervention was a predictor of neuroprotection (g 0.07, SE 0.03, p 0.01 per every mmol/L increase in ketone levels). Ketosis exerts a potent neuroprotection against acute damage to the mammalian CNS in terms of reduction of mortality, of neuronal damage and dysfunction. Hematic levels of ketones are directly proportional to the effect size of neuroprotection.