Processes In Central Nervous System Research Articles

PIEZO1-Related Physiological and Pathological Processes in CNS: Focus on the Gliomas.

PIEZO1 is ubiquitously expressed in cells in different kinds of tissues throughout the body, which can sense physical or mechanical stimuli and translate them into intracellular electrochemical signals to regulate organism functions. In particular, PIEZO1 appears in complex interactive regulatory networks as a central node, governing normal and pathological functions in the body. However, the effect and mechanism of the activation or expression of PIEZO1 in diseases of the central nervous system (CNS) remain unclear. On one hand, in CNS diseases, pathophysiological processes in neurons and glial are often accompanied by variations in the mechanical properties of the cellular and extracellular matrix stiffness. The expression of PIEZO1 can therefore be upregulated, in responding to mechanical stimulation, to drive the biological process in cells, which in turns indirectly affects the cellular microenvironment, resulting in alterations of the cellular status. On the other hand, it may have contradictory effects with the change of active patterns and/or subcellular location. This review highlights the biological processes involved with PIEZO1 in CNS cells, with special emphasis on its multiple roles in glioma-associated phenotypes. In conclusion, PIEZO1 can be used as an indicator to assess the malignancy and prognosis of patients with gliomas, as well as a therapeutic target for clinical application following fully exploring the potential mechanism of PIEZO1 in CNS diseases.

Protective roles of adropin in neurological disease.

Adropin is a highly conserved secreted peptide encoded by the Energy Homeostasis Associated gene (Enho). It is expressed in many tissues throughout the body, including the liver and brain, and plays a crucial role in maintaining lipid homeostasis and regulating insulin sensitivity. Adropin also participates in several other pathophysiological processes of multiple central nervous system (CNS) diseases. There is strong evidence of the protective effects of adropin in stroke, heart disease, aging, and other diseases. The peptide has been shown to reduce the risk of disease, attenuate histological alterations, and reduce cognitive decline associated with neurological disorders. Recent findings support its critical role in regulating endothelial cells and maintaining blood-brain barrier integrity through an endothelial nitric oxide synthase (eNOS)-dependent mechanism. Here we discuss current evidence of the protective effects of adropin in CNS diseases specifically involving the cerebrovasculature and highlight potential mechanisms through which the peptide exhibits these effects.

Neuroinflammation of traumatic brain injury: Roles of extracellular vesicles.

Traumatic brain injury (TBI) is a major cause of neurological disorder or death, with a heavy burden on individuals and families. While sustained primary insult leads to damage, subsequent secondary events are considered key pathophysiological characteristics post-TBI, and the inflammatory response is a prominent contributor to the secondary cascade. Neuroinflammation is a multifaceted physiological response and exerts both positive and negative effects on TBI. Extracellular vesicles (EVs), as messengers for intercellular communication, are involved in biological and pathological processes in central nervous system (CNS) diseases and injuries. The number and characteristics of EVs and their cargo in the CNS and peripheral circulation undergo tremendous changes in response to TBI, and these EVs regulate neuroinflammatory reactions by activating prominent receptors on receptor cells or delivering pro- or anti-inflammatory cargo to receptor cells. The purpose of this review is to discuss the possible neuroinflammatory mechanisms of EVs and loading in the context of TBI. Furthermore, we summarize the potential role of diverse types of cell-derived EVs in inflammation following TBI.

The Expression of miRNAs Involved in Long-Term Memory Formation in the CNS of the Mollusk Helix lucorum

Mollusks are unique animals with a relatively simple central nervous system (CNS) containing giant neurons with identified functions. With such simple CNS, mollusks yet display sufficiently complex behavior, thus ideal for various studies of behavioral processes, including long-term memory (LTM) formation. For our research, we use the formation of the fear avoidance reflex in the terrestrial mollusk Helix lucorum as a learning model. We have shown previously that LTM formation in Helix requires epigenetic modifications of histones leading to both activation and inactivation of the specific genes. It is known that microRNAs (miRNAs) negatively regulate the expression of genes; however, the role of miRNAs in behavioral regulation has been poorly investigated. Currently, there is no miRNAs sequencing data being published on Helix lucorum, which makes it impossible to investigate the role of miRNAs in the memory formation of this mollusk. In this study, we have performed sequencing and comparative bioinformatics analysis of the miRNAs from the CNS of Helix lucorum. We have identified 95 different microRNAs, including microRNAs belonging to the MIR-9, MIR-10, MIR-22, MIR-124, MIR-137, and MIR-153 families, known to be involved in various CNS processes of vertebrates and other species, particularly, in the fear behavior and LTM. We have shown that in the CNS of Helix lucorum MIR-10 family (26 miRNAs) is the most representative one, including Hlu-Mir-10-S5-5p and Hlu-Mir-10-S9-5p as top hits. Moreover, we have shown the involvement of the MIR-10 family in LTM formation in Helix. The expression of 17 representatives of MIR-10 differentially changes during different periods of LTM consolidation in the CNS of Helix. In addition, using comparative analysis of microRNA expression upon learning in normal snails and snails with deficient learning abilities with dysfunction of the serotonergic system, we identified a number of microRNAs from several families, including MIR-10, which expression changes only in normal animals. The obtained data can be used for further fundamental and applied behavioral research.

Effects of a maximal cycling all-out anaerobic test on visual performance

ABSTRACT Clinical relevance All-out exercise may not impair all central nervous system processes, such as those related to visual-motor abilities, and may actually prove stimulatory to such tasks allowing athletes and sports conditioning specialists to develop strategies to take advantage of/mitigate the effects of such exercise on athletic performance. Background Despite research indicating that visual-motor abilities play a critical role in athletic performance, research has primarily focused on the effect of all-out exercise on processes along the motor pathway, such as resultant force production or simple cognitive tasks. Such research has neglected to investigate the effect of all-out exercise on visual tasks. When investigations on visual tasks are forthcoming, they focus on prolonged aerobic exercise, which is not the primary metabolic pathway for all, or even the majority of sports. Methods Sixty untrained males (experimental group; N = 30, control group; N = 30) completed a standardised six-item baseline sports vision test battery and one week later, the experimental participants returned to undertake a 30-second Wingate anaerobic test (30-WAnT) immediately followed by the same test battery. Results Significant (P < 0.05) improvements were found in accommodation facility, saccadic eye movement, speed of recognition, peripheral awareness and hand-eye coordination (P < 0.001 for all), but not visual memory (P = 0.242) following the 30-WAnT. Conclusions Although the mechanisms underlying these improvements in visual task performance have not yet been studied, this study suggests that simple anaerobic all-out exercise does not cause central- or brain-based fatigue impairing the oculomotor system but may rather provide “excitability” of the underlying motor cortex, motoneurons and/or corticofugal connections utilised in visual task response. It appears that the sweeping improvements in visual task performance elucidate the need for an intense anaerobic warm-up when training visual skills and when visual skills form an integral part of athletic performance.

Inhibition of the LRRC8A channel promotes microglia/macrophage phagocytosis and improves outcomes after intracerebral hemorrhagic stroke.

Promoting microglial/macrophage (M/Mφ) phagocytosis accelerates hematoma clearance and improves the prognosis of intracerebral hemorrhagic stroke (ICH). Cation channels such as Piezo1 modulate bacterial clearance by regulating M/Mφ. Whether LRRC8A, an anion channel, affects M/Mφ erythrophagocytosis and functional recovery after ICH was investigated here. We found that LRRC8A is highly expressed on M/Mφ in the perihematomal region of ICH mice. Conditional knockout of Lrrc8a in M/Mφ or treatment with an LRRC8A channel blocker accelerated hematoma clearance, reduced neuronal death, and improved functional recovery after ICH. Mechanistically, the LRRC8A channel inhibition promoted M/Mφ phagocytosis by activating AMP-activated protein kinase (AMPK), thereby inducing nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and increasing Cd36 transcription. Our findings illuminate the regulation of M/Mφ phagocytosis by the LRRC8A channel via the AMPK-Nrf2-CD36 pathway after ICH, suggesting that LRRC8A is a potential target for hematoma clearance in ICH treatment.

Relationship Between Temporal Pattern Perception Test and Mismatch Negativity in Children With Auditory Processing Disorder and Dyslexia.

Mismatch negativity (MMN) is an objective test for assessing auditory function. The central auditory nervous system processes different stimuli in various ways. This can be assessed using MMN elicited with different stimuli in an "oddball" paradigm. This study evaluated temporal ordering skills using MMN with different durations of stimuli. This study aimed to determine the correlation between the results of the behavioral duration pattern test (DPT) with MMN in typically developing children versus children with dyslexia and auditory processing disorder (APD). Subjects and. Two groups of children participated in the study. The experimental group included 16 children with APD and dyslexia who had scored below the age-matched scores in the DPT. The control group consisted of 16 typically developing children with age-matched scores in the DPT. MMN was elicited using the same stimuli (250 ms and 500 ms) as that of the DPT in both groups. MMN latency, MMN amplitude, and area under the curve were measured in both groups. Compared to the control group, children with APD and dyslexia showed increased MMN latency, reduced amplitude, and decreased area under the curve. There was a low correlation (r= -0.293, p<0.05) between MMN latency and DPT scores. The correlation between MMN amplitude and DPT scores was moderate (0.472, p<0.001). Furthermore, a strong correlation (0.536, p<0.001) between area under the curve and DPT scores was demonstrated. MMN amplitude and MMN area under the curve could serve as valid indicators during assessment of temporal ordering in children with APD and dyslexia.

Ascorbic acid 6-palmitate modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated BV-2 cells via PERK/elF2α mediated endoplasmic reticulum stress

BackgroundNeuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells.MethodsImmortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK).ResultsL-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation.ConclusionTogether, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.

Bergaptol Alleviates LPS-Induced Neuroinflammation, Neurological Damage and Cognitive Impairment via Regulating the JAK2/STAT3/p65 Pathway

Neuroinflammation is considered a critical pathological process in various central nervous system (CNS) diseases and is closely related to neuronal death and dysfunction. Bergaptol is a natural 5-hydroxyfurocoumarin found in lemon, bergamot and other plants. Some studies have confirmed its anti-cancer, anti-inflammatory and anti-atherogenic functions, indicating that it may have significant medicinal value. In this study, we investigated the potential effect of Bergaptol in vitro and in vivo neuroinflammatory models. Mice were injected with LPS (40 μg/kg) into the hippocampal CA1 region and then injected intraperitoneally with Bergaptol (10, 20 and 40 mg/kg) once a day for two weeks. In addition, to verify the effect of Bergaptol on BV2 cells, Bergaptol with different concentrations (5, 10 and 20 μg/mL) was firstly incubated for 1 hour, then LPS with a concentration of 1 μg/mL was added and incubated for 23 hours. Bergaptol treatment significantly improved the cognitive impairment induced by LPS. In addition, Bergaptol significantly inhibited the reduction of dendritic spines and the mRNA level of inflammatory factors (TNF-α, IL-6 and IL-1β) in hippocampal induced by LPS. In vitro, Bergaptol inhibited the production of TNF-α, IL-6 and IL-1β from LPS-treated BV-2 cells. In addition, Bergaptol treatment significantly reduced the phosphorylation levels of JAK2, STAT3 and p65 in LPS-stimulated BV-2 cells. In conclusion, our results suggest that Bergaptol alleviates LPS-induced neuroinflammation, neurological damage and cognitive impairment by regulating the JAK2/STAT3/P65 pathway, suggesting that Bergaptol is a promising neuroprotective agent.

Lysophosphatidic acid signaling via LPA6 : A negative modulator of developmental oligodendrocyte maturation.

The developmental process of central nervous system (CNS) myelin sheath formation is characterized by well-coordinated cellular activities ultimately ensuring rapid and synchronized neural communication. During this process, myelinating CNS cells, namely oligodendrocytes (OLGs), undergo distinct steps of differentiation, whereby the progression of earlier maturation stages of OLGs represents a critical step toward the timely establishment of myelinated axonal circuits. Given the complexity of functional integration, it is not surprising that OLG maturation is controlled by a yet fully to be defined set of both negative and positive modulators. In this context, we provide here first evidence for a role of lysophosphatidic acid (LPA) signaling via the G protein-coupled receptor LPA6 as a negative modulatory regulator of myelination-associated gene expression in OLGs. More specifically, the cell surface accessibility of LPA6 was found to be restricted to the earlier maturation stages of differentiating OLGs, and OLG maturation was found to occur precociously in Lpar6 knockout mice. To further substantiate these findings, a novel small molecule ligand with selectivity for preferentially LPA6 and LPA6 agonist characteristics was functionally characterized in vitro in primary cultures of rat OLGs and in vivo in the developing zebrafish. Utilizing this approach, a negative modulatory role of LPA6 signaling in OLG maturation could be corroborated. During development, such a functional role of LPA6 signaling likely serves to ensure timely coordination of circuit formation and myelination. Under pathological conditions as seen in the major human demyelinating disease multiple sclerosis (MS), however, persistent LPA6 expression and signaling in OLGs can be seen as an inhibitor of myelin repair. Thus, it is of interest that LPA6 protein levels appear elevated in MS brain samples, thereby suggesting that LPA6 signaling may represent a potential new druggable pathway suitable to promote myelin repair in MS.

Regulation of Glial Function by Noncoding RNA in Central Nervous System Disease.

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.

Herbal Approaches to Pediatric Functional Abdominal Pain.

Chronic abdominal pain is one of the most common problems seen by both pediatricians and pediatric gastroenterologists. Abdominal-pain-related functional gastrointestinal disorders (AP-FGIDs) are diagnosed in children with chronic and recurrent abdominal pain meeting clinical criteria set forth in the Rome IV criteria. AP-FGIDs affect approximately 20% of children worldwide and include functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain (FAP), and abdominal migraine. IBS accounts for 45% of pediatric AP-FGIDs. The pathophysiology of functional abdominal pain involves an interplay of factors including early life events, genetics, psychosocial influences, and physiologic factors of visceral sensitivity, motility disturbance, altered mucosal immune function, and altered central nervous system processing. Treatment approaches are varied and can include dietary, pharmacologic, and complementary medicine interventions, as well as psychosocial support, depending on the many aspects of the disorder and the needs of the individual patient. There is a strong interest in complementary and integrative medicine approaches to pediatric pain from both patients, providers, and families. In this article, we discuss popular herbal treatments typically used in the field of complementary medicine to treat pediatric AP-FGIDs: peppermint oil, Iberogast®, cannabis, fennel, and licorice. While high-quality data are rather limited, studies generally show that these remedies are at least as effective as placebo, and are well tolerated with minimal side effects. We will need more placebo-controlled, double-blind, and unbiased prospective studies to document and quantify efficacy.

Preliminary brain-behavioral neural correlates of anterior cruciate ligament injury risk landing biomechanicsusing a novelbilateral leg press neuroimaging paradigm.

Anterior cruciate ligament (ACL) injury risk reduction strategies primarily focus on biomechanical factors related to frontal plane knee motion and loading. Although central nervous system processing has emerged as a contributor to injury risk, brain activity associated with the resultant ACL injury-risk biomechanics is limited. Thus, the purposes of this preliminary study were to determine the relationship between bilateral motor control brain activity and injury risk biomechanics and isolate differences in brain activity for those who demonstrate high versus low ACL injury risk. Thirty-one high school female athletes completed a novel, multi-joint leg press during brain functional magnetic resonance imaging (fMRI) to characterize bilateral motor control brain activity. Athletes also completed an established biomechanical assessment of ACL injury risk biomechanics within a 3D motion analysis laboratory. Knee abduction moments during landing were modelled as a covariate of interest within the fMRI analyses to identify directional relationships with brain activity and an injury-risk group classification analysis, based on established knee abduction moment cut-points. Greater landing knee abduction moments were associated with greater lingual gyrus, intracalcarine cortex, posterior cingulate cortex and precuneus activity when performing the bilateral leg press (all z > 3.1, p < .05; multiple comparison corrected). In the follow-up injury-risk classification analysis, those classified as high ACL injury-risk had greater activity in the lingual gyrus, parietal cortex and bilateral primary and secondary motor cortices relative to those classified as low ACL injury-risk (all z > 3.1, p < .05; multiple comparison corrected). In young female athletes, elevated brain activity for bilateral leg motor control in regions that integrate sensory, spatial, and attentional information were related to ACL injury-risk landing biomechanics. These data implicate crossmodal visual and proprioceptive integration brain activity and knee spatial awareness as potential neurotherapeutic targets to optimize ACL injury-risk reduction strategies.

Multisensory sensitivity differentiates between multiple chronic pain conditions and pain-free individuals.

Multisensory sensitivity (MSS) to nonpainful stimuli has been identified as a risk factor for the presence of coexisting chronic pain conditions. However, it remains unclear whether MSS can differentiate pain phenotypes involving different levels of central sensitivity. Both pain-free and those with chronic pain, particularly fibromyalgia (FM), migraine, or low back pain (LBP) were recruited, with pain comorbidities assessed. MSS was highest in FM, followed by migraine, then LBP, and lowest in pain-free individuals (adjusted between condition Cohen d = 0.32-1.2, P ≤ 0.0007). However, when secondly grouping patients by the total number of pain comorbidities reported, those with a single pain condition (but not FM) did not have significantly elevated MSS vs pain-free individuals (adj d= 0.17, P = 0.18). Elevated MSS scores produced increased odds of having 2 or more pain comorbidities; OR [95% CI] =2.0 [1.15, 3.42], without, and 5.6 [2.74, 11.28], with FM ( P ≤ 0.0001). Furthermore, those with low MSS levels were 55% to 87% less likely to have ≥ 2 pain comorbidities with or without FM (OR 0.45 [0.22, 0.88]-0.13 [0.05, 0.39]; P ≤ 0.0001). Our findings support that MSS can differentiate between pain phenotypes with different degrees of expected central mechanism involvement and also serve as a risk and resilience marker for total coexisting chronic pain conditions. This supports the use of MSS as a marker of heightened central nervous system processing and thus may serve as a clinically feasible assessment to better profile pain phenotypes with the goal of improving personalized treatment.

Impact of Nuclear Envelope Stress on Physiological and Pathological Processes in Central Nervous System.

The nuclear envelope (NE) separates genomic DNA from the cytoplasm and provides the molecular platforms for nucleocytoplasmic transport, higher-order chromatin organization, and physical links between the nucleus and cytoskeleton. Recent studies have shown that the NE is often damaged by various stresses termed "NE stress", leading to critical cellular dysfunction. Accumulating evidence has revealed the crucial roles of NE stress in the pathology of a broad spectrum of diseases. In the central nervous system (CNS), NE dysfunction impairs neural development and is associated with several neurological disorders, such as Alzheimer's disease and autosomal dominant leukodystrophy. In this review, the structure and functions of the NE are summarized, and the concepts of NE stress and NE stress responses are introduced. Additionally, the significant roles of the NE in the development of CNS and the mechanistic connections between NE stress and neurological disorders are described.

Interaction between TMEFF1 and AHNAK proteins in ovarian cancer cells: Implications for clinical prognosis

TMEFF1 is a newly discovered protein involved in the physiological functions of the central nervous system, embryonic development, and other biological processes. Our previous study revealed that TMEFF1 acts as a tumor-promoting gene in ovarian cancer. AHNAK, as a giant scaffolding protein, plays a role in the formation of the blood–brain barrier, cell architecture and the regulation of cardiac calcium channels. However, its role in ovarian cancer remains poorly researched. In this study, we detected the expression of AHNAK and TMEFF1 in 148 different ovarian cancer tissues, determined their relationship with pathological parameters and prognosis, clarified the interaction between the two proteins, and explored the related cancer-promoting mechanisms through immunohistochemistry, immunoprecipitation, immunofluorescence double staining, western blotting, and bioinformatics. The high expression of ANHAK and TMEFF1 in ovarian cancer indicated a higher degree of tumor malignancy and a worse prognosis. Furthermore, the expression of TMEFF1 and AHNAK was significantly positively correlated. The results also showed that AHNAK and TMEFF1 co-localized and interacted with each other in ovarian cancer tissues and cells. And knockdown of AHNAK promoted proliferation, migration and invasion of ovarian cancer cells in vitro. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that AHNAK and related genes were enriched during mitosis regulation, cytoskeleton formation, gene epigenetics, etc., whereas TMEFF1 and related genes are enriched during immune regulation and other processes. We also clarified the network of kinases, microRNA, and transcription factor targets, and the impact of genetic mutations on prognosis. Notably, AHNAK was regulated by the expression of TMEFF1 and can activate the MAPK pathways. Overall, high expression of AHNAK and TMEFF1 in ovarian cancer cells indicated a higher degree of tumor malignancy and a worse prognosis. Therefore, the interaction between AHNAK and TMEFF1 may become a potential anti-tumor target for ovarian cancer treatment.

Magnesium sulphate within multimodal analgesia, pre-emptive, or preventive analgesia

BackgroundMagnesium (Mg) is a non-competitive N-methyl d-aspartate receptor antagonist with antinociceptive effects. Multimodal therapy is the optimal strategy for perioperative pain control to minimize the need for opioids. Inflammation caused by tissue trauma or direct nerve injury is responsible for the perioperative pain. The concept of “pre-emptive” analgesia, analgesic strategies administered prior to the stimulus, can modify the peripheral and central nervous system processing of noxious stimuli, thereby reducing central sensitization, hyperalgesia, and allodynia remains controversial. A more encompassing approach to the reduction of postoperative pain is the concept of “preventive” analgesia. The purpose of the study is to detect the proper use of MgSO4 as an analgesic being a non-competitive N-methyl d-aspartate (NMDA).ResultsThere is no statistically significant difference in the haemodynamic parameters, intraoperative (33% vs 20%) and postoperative requirement for analgesics 6.6% vs 10% among groups I and II, respectively. There is no significant difference in the numerical analogue scale, where 16 vs 17 patients with no pain, 12 vs 10 with mild pain, and 2 vs 3 with moderate pain in groups I and II, respectively.ConclusionThe use of MgSO4 in a bolus with or without infusion is comparable in the control of intraoperative and postoperative pain.

Assessment of the YKL-40 concentration in patients with tick-borne encephalitis

Tick-borne encephalitis (TBE) is a viral infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV). It might take several clinical courses such as: meningitis, meningoencephalitis or meningoencephalomyelitis. The aim this study was to compare the YKL-40 concentration in cerebrospinal fluid (CSF) of patients with different clinical presentations of TBE and patients with excluded meningitis (control group). The concentration of YKL-40 in CSF was determined using Fujirebio tests (Ghent, Belgium) in 32 patients with TBE: Group I—patients with meningoencephalitis (n = 16); Group II—patients with meningitis (n = 16). The control group (CG) consisted of 17 patients in whom any inflammatory process in central nervous system was excluded. The concentration of YKL-40 was significantly higher in encephalitis group than in the CG after 7 days from the last dose of treatment. The concentration in patients with neuroinflammation had a significantly different concentration of YKL-40 compared to patients from the neuroinflammation control group. The ROC curve analysis indicates that CSF YKL-40 concentration at cut-off 783.87 differentiated TBE patients from CG with 100% specificity and 70% sensitivity and CSF YKL-40 concentration at cut-off 980.11 differentiated meningitis from meningoencephalitis with 87.5% specificity and 62.5% sensitivity. YKL-40 takes part in TBE pathogenesis, its concentration is the highest at the early stage of CNS involvement and decreases in the convalescent period. As YKL-40 was significantly higher in the meningitis than in the meningoencephalitis group, it might be used as biomarker in differentiation of these clinical forms of TBE.

A study to assess reaction time and its association with adiposity indices in healthy individuals in Uttarakhand

Introduction: Reaction time is the central indicator of the central nervous system's sensorimotor coordination and processing skills, as well as coordinated peripheral movement response. There is a substantial positive link between body mass index (BMI) and reaction time. However, no studies on the impact of old and novel adiposity indices on cognitive capacity measurement have been done. As a result, this study was carried out to see if there was a link between visceral adiposity index (VAI) and lipid accumulation product (LAP) and reaction time in healthy Uttarakhand residents. Materials and Methods: The observational study was conducted in 2018 from January to June at AIIMS, Rishikesh to screen 89 individuals aged 20–40 years, who were in good health and lived in adjacent areas to examine reaction time simple reaction time (SRT) and choice reaction time [CRT]) and its relationship with adiposity indices. The Deary-Liewald reaction time task (software) was used to examine the participants' reaction time, which was followed by anthropometric measurements and other biochemical tests. Results: Among 89 individuals, 61% were male and 39% were female. In terms of age, BMI, waist circumference (WC), waist-to-hip ratio, and response time, there was no significant difference between males and females. However, males had a faster reaction time than females. VAI is substantially higher in females than in males. Females have more LAP than males, although the difference is not statistically significant. Conclusion: LAP had a substantially better association than BMI and WC in the case of females with respect to the association with CRT because LAP includes both anthropometric WC and lipid parameters (triglycerides). In healthy people, LAP could be recommended as a superior indicator for assessing response time as a measure of cognitive ability.

Gadd45 in Neuronal Development, Function, and Injury.

The growth arrest and DNA damage-inducible (Gadd) 45 proteins have been associated with numerous cellular mechanisms including cell cycle control, DNA damage sensation and repair, genotoxic stress, neoplasia, and molecular epigenetics. The genes were originally identified in in vitro screens of irradiation- and interleukin-induced transcription and have since been implicated in a host of normal and aberrant central nervous system processes. These include early and postnatal development, injury, cancer, memory, aging, and neurodegenerative and psychiatric disease states. The proteins act through a variety of molecular signaling cascades including the MAPK cascade, cell cycle control mechanisms, histone regulation, and epigenetic DNA demethylation. In this review, we provide a comprehensive discussion of the literature implicating each of the three members of the Gadd45 family in these processes.