Search

Reactive astrogliosis is one of the most frequency neuropathological alterations in the hippocampus of animal models and patients with temporal lobe epilepsy (TLE). Valproic acid (VPA), a widely used antiepileptic drug (AED), acts by blocking ion channels and enhancing GABAergic activity. This study investigated the effects of VPA on hippocampal astrogliosis in a rat model of TLE. The results demonstrated that chronic administration of VPA at a dose of 200 mg/kg significantly reduced the severity of astrogliosis and ameliorated neuronal loss in the hippocampus at the early and middle stages post-status epilepticus (SE), while also improving cognitive impairments at the middle and late stages in KA-SE rats. Long-term administration of VPA at 400 mg/kg attenuated astrogliosis in the hippocampus at the middle stage post-SE, but lacked neuroprotective effects and exacerbated cognitive impairments at the late stage. These findings suggest that VPA at an appropriate dose could mitigate hippocampal astrogliosis, potentially offering a new antiepileptic mechanism for its long-term use.

Objectives: Stroke is the second leading cause of global death and is characterized by excitotoxic neuronal death caused by NMDA (N-Methyl-D-Aspartate) receptor overactivation. The present study was conducted to investigate the therapeutic potential of IC87201, a novel small molecule interfering with the NMDA receptor intracellular signaling pathway, in reducing the extent of ischemic stroke-induced brain damage. Materials and Methods: Cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) method in 24 anesthetized adult male rats for one hour. The animals were randomized into sham, MCAO, MCAO+ DXM (Dextromethorphan hydrobromide monohydrate) as an NMDA antagonist, and MCAO+ IC87201 groups which in the last two groups, DXM (50 mg/kg) and IC87201 (10 mg/kg) were injected intraperitoneally after ischemia. The neurobehavioral scores were appraised for 7 days and after that, brain tissue was appropriately prepared to perform the stereological evaluations. Results: The administration of IC87201 significantly recovered post-ischemia damages, including neurobehavioral function, reduction of volume of the total hemisphere, cortex, and striatum in rat brain, and the percentage of infarcted areas. Additionally, in the striatum region, IC87201 caused an increase in the total number of neuronal and non-neuronal cells as well as a decrease in the total number of dead cells. Some of these parameters were improved by DXM, but in general, IC87201 outperformed that. Conclusions: IC87201 was successful in minimizing ischemia-induced damage, especially in the striatal region. In addition, IC87201, as a molecule that acts on the intracellular signaling cascade of the NMDA receptor, performed better than DXM, as an antagonist of this receptor.

Schizophrenia (SCZ) is a common psychiatric disorder that has a complex pathological mechanism. During the Coronavirus disease 2019 (COVID-19) epidemic, patients with SCZ had substantially higher rates of infection with SARS-CoV-2, the virus that causes COVID-19, as well as higher COVID-19 mortality relative to patients with other mental disorders. However, the reasons for these increased rates in patients with SCZ remain unknown. In this review, we hypothesize that certain molecular pathways exhibit abnormal function in both COVID-19 and SCZ, with a focus on those related to energy metabolism dysregulation, immune system disruption, and abnormalities of the central nervous system. We review that dysregulation of energy metabolism can result in disruptions to the immune system and abnormalities within the central nervous system (CNS). Furthermore, immune system disturbances may also contribute to CNS abnormalities in both SCZ and COVID-19. We also discuss macro-factors associated with the high infection and mortality rates of COVID-19 in patients with SCZ, including sociodemographic factors, reduced access to psychiatric healthcare, structural barriers to COVID-19 vaccination, and proposed approaches to mitigate these macro-factors.

Given the high prevalence of tinnitus and anxiety among patients, understanding the mechanisms that increase anxiety is crucial. Neuroligin 2 (NLGN2) is an anxiety-related protein that has received much attention in recent years. On the other hand, the Brain-Derived Neurotrophic Factor (BDNF) affects various neurotransmitter systems, neuropeptides, and intracellular signaling pathways. These are neurochemical systems that, if out of balance, could lead to anxiety behavior. This is the first study to investigate whether changes in protein expression in the amygdala nucleus are associated with high anxiety in tinnitus. After inducing and confirming tinnitus in rats using gap-prepulse inhibition of the acoustic startle (GPIAS) and Pre-pulse inhibition (PPI), the Elevated Plus Maze (EPM) and the Open Field Test (OFT) were used to assess anxiety levels in both groups. Subsequently, amygdala tissue samples were collected from both groups and analyzed for NLGN2 and BDNF protein expression. The GPIAS score decreased following sodium salicylate administration in the tinnitus group, while the PPI score did not change. Additionally, the tinnitus group exhibited higher anxiety levels than the control group in both behavioral tests. Moreover, NLGN2 protein expression was increased in the amygdala nucleus of sodium salicylate-induced tinnitus rats compared to controls, while BDNF protein expression was reduced. These findings suggest that increased NLGN2 and decreased BDNF protein levels in the amygdala nucleus contribute to tinnitus-related anxiety and identify these proteins as potential therapeutic targets for tinnitus.

Introduction: Neurofibrillary tangles (NFTs) are composed of hyperphosphorylated forms of microtubule-associated protein tau (Tau), which is responsible for neurodegeneration in Alzheimer’s disease (AD). The hippocampal region has been a major focus of AD research because the deposits of phosphorylated tau protein in these regions are correlated with early memory deficits. Despite extensive studies, therapeutic strategies to reduce tau hyperphosphorylation and NFTs deposition remain unclear. AL04, a recently developed recombinant fusion protein comprising Cystatin C, human serum albumin, and a novel blood brain barrier (BBB) penetrating peptide, is currently under investigation. Previous studies have demonstrated its effectiveness in reducing amyloid beta plaques in AD mouse model. Methods: In this study, we investigated the effects of AL04 on lowering hyperphosphorylated tau and NFTs in JNPL3 mouse model harboring human tau-P301L mutation. 3-month-old female mice intraperitoneally received AL04 (5 mg/kg) or PBS treatment every other week for 24 weeks. We used confocal microscopy and western blot to visualize and analyze changes in hyperphosphorylated tau Ser202/Thr205 labeled with AT8 antibody in the brain. Results: We found that the AL04 treatment decreases hyperphosphorylated tau at PP2A-sensitive epitope Ser202/Thr205 in the hippocampus of the brain. In the brain lysates of AL04 treated mice, we observed the reduction of I2PP2A, inhibitor of PP2A, and the induction of autophagy receptor proteins such as SQSTM-1/p62 and OPTN. Conclusion: Our data suggests that AL04 can be used as an AD prophylactic/therapeutic agent as it lowers the hyperphosphorylated tau by downregulating I2PP2A. We also propose that AL04 can induce the degradation of hyperphosphorylated tau aggregates through the upregulation of the autophagy pathway.

In the era of rapid digitalization, the widespread integration of digital technology into various aspects of daily life has sparked significant interest in understanding its impact on cognitive mental processes. While the emerging data suggests that its influence may be positive or negative, the depth of evidence regarding neurobiological mechanisms remains limited. This review aims to synthesize previously published studies and develop a comprehensive framework that systematically categorizes digital technologies, the cognitive functions they impact, and developmental stages around the concept of neuroplasticity, while clearly illustrating their interconnections. Despite acknowledged limitations, through an exhaustive approach, this paper intends to offer a dynamic perspective on the effects of digital media on the human brain, before the onset of addiction.

Background: This study aims to evaluate the clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS) when used as an add-on therapy for individuals with persistent postural-perceptual dizziness (PPPD). Methods: In this randomized controlled, double-blind trial conducted at Shangluo Central Hospital, patients with PPPD diagnosed in the neurology departments were included. Participants were randomized into a rTMS treatment group and a control group in a 1:1 ratio by the randomized grouping method. Patients in both groups received conventional treatment, with the rTMS treatment group underwent daily rTMS sessions, whereas the control group received sham rTMS treatments following the same schedule. The effectiveness of the treatments was primarily assessed using the Dizziness Handicap Inventory (DHI), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD), which measured symptoms of vertigo, anxiety, and depression at baseline, after two weeks, and at the end of four weeks. Findings: Of the 46 participants recruited, 2 were excluded due to contraindications, 22 were randomly assigned to the rTMS treatment group, and 22 were assigned to the control group. Ultimately, 2 withdrew for personal reasons, and data from 42 participants were included in the outcome analysis. HAMA, HAMD and DHI scores were significantly lower in the rTMS treatment group than in the control group after 4 weeks of treatment (p

Introduction: Processes that generate systemic inflammation are strongly associated with neurodegenerative diseases. This study aimed to explore the potential anti-oxidative and anti-inflammatory effects of fasudil and its role in modulating aquaporin-4 (AQP-4) to improve cognitive impairment in a systemic inflammation model induced by lipopolysaccharide (LPS). Method: fourty C57BL/6 mice were assigned to four groups, including sham, LPS, sham+fasudil, and LPS+fasudil). Intraperitoneal LPS was given (500 μg/kg/day) at hours 0, 24, 48, and 72, and fasudil (30 mg/kg) administered intraperitoneal injections 2 hours after LPS injection. The open field, Y-maze, and Novel object tasks was used to assess learning and memory. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the hippocampus also measured as markers of oxidative stress and inflammation. Furthermore, the expression of AQP-4 measured in the intact and experimental groups. Results: The results showed that Fasudil significantly improved memory and anxiety behavior induced by LPS in the open field maze, spatial recognition memory in the Y-maze, and performance in the novel object recognition task. It also mitigates hippocampal MDA and SOD levels. Additionally, fasudil ameliorated LPS-induced hippocampal levels of TNFα and IL-10 and increased hippocampal levels of AQP-4 expression in mice. Conclusion: Our results suggest that fasudil in the LPS model of systemic inflammation could improve cognition by suppressing oxidative stress and inflammation and increasing AQP-4 protein expression. These findings highlighted the potential of fasudil as a neuroprotective agent. However, further research is required to fully understand its neuroprotective properties in the treatment of neurodegenerative disorders.

In Cameroon, epilepsy is one of the most common neurological diseases. Available anti-epileptic medication, on the other hand, have been associated with pharmacological toxicity and emotional impairment. The identification of a more efficient replacement is critical. Recent research reveals that ferroptosis contributes to the pathophysiology of epilepsy and related anxiety disorders. Lantana camara is a plant with a high neuropharmacological potential, but its mechanisms of action have yet to be understood. The purpose of this study was to determine the effect of ethanolic and aqueous extracts of Lantana camara on the kainate model of epilepsy in mice. The focus was on these extracts' capacity to suppress ferroptosis. Mice were injected with kainate (12 mg/kg, i.p.) to induce epilepsy. After status epilepticus, animals were left for 19 days, which correspond to an epileptogenic period. After the appearance of spontaneous recurrent seizures, mice were treated with distilled water (10 ml/kg, p.o.), levetiracetam (80 mg/kg, p.o.), sodium valproate (300 mg/kg, p.o.), ethanolic extract of L. camara (230, 460, 920 mg/kg, p.o.), or an aqueous extract of L. camara (460 mg/kg p.o.). These treatments lasted for 14 days. During this period, the number and duration of seizures were recorded. The mice were then subjected to elevated zero-maze and open field tests to assess anxiety-like behavior. At the end, mice were sacrificed and hippocampus, amygdala, and striatum were dissected out for biochemical and histological analyses. The extracts alleviated seizure- and anxiety-like behavior in KA-treated mice. Decreased iron levels, reflected by a decrease in ferritin levels and a increase in transferrin levels, were observed in the hippocampus, striatum and amygdala of the extract-treated group compared to the KA-treated group. In addition, increase in GABA and GSH levels, and a decrease in MDA levels were observed in these groups. Hematoxylin-eosin staining revealed less pronounced neuronal degeneration and a more sustained architecture in the brain region of extract-treated mice. These findings indicated that ethanolic and aqueous extracts of L. camara effectively attenuate seizures and anxiety disorders. Probable mechanisms of action include GABAergic, iron, GSH, and MDA modulations.

Background: Early detection of spinal cord injury (SCI) is conducive to improving patient outcomes. In addition, many studies have revealed the role of immune cells in the progression or treatment of SCI. The objective of this study was to identify the early signature genes and clarify how they are related to immune cell infiltration in SCI. Methods: We analysed and identified early signature genes associated with SCI via bioinformatics analysis of the GSE151371 dataset from the GEO database. These genes were subsequently verified in the GSE33886 dataset and qRTPCR. Finally, the CIBERSORT algorithm was used to examine the immune cell infiltration in SCI and its relationship with signature genes. Results: Seven SCI-related signature genes, including ARG1, RETN, BPI, GGH, CCNB1, HIST1H2AC, and HIST1H2BJ, were identified, and their expression was verified via an external validation cohort and qRTPCR. Moreover, the ROC curves revealed the diagnostic value of these genes. In addition, on the basis of immune cell infiltration analysis, plasma cells, M0 macrophages, activated CD4+ memory T cells, γδ T cells, naive CD4+ T cells, and resting CD4+ memory T cells may participate in the progression of SCI. Conclusion: This study identified seven early signature genes of SCI that may serve as biomarkers for the early diagnosis of SCI and contribute to our understanding of immune changes during the pathology of SCI.

Autism spectrum disorder (ASD) and Huntington's disease (HD) are complex neurological conditions with unclear causes and limited treatments, affecting individuals, families, and society. Despite ASD and HD representing two opposing stages of neuronal development and degeneration, they share similar clinical-pathological features in motor function. In this study, we leveraged transcriptomic data from the prefrontal cortex available in public databases to identify shared transcriptional characteristics of ASD and HD. Differential expression analysis revealed that the majority of differentially expressed genes (DEGs) were up-regulated in ASD carriers, whereas most DEGs were down-regulated in HD carriers. Among the DEGs shared between both diseases, three out of seven protein-coding genes were related to the immune system. Furthermore, we identified two enriched pathways shared between ASD and HD DEGs. The gene interaction network analysis unveiled four hub genes shared by both diseases, all of which are associated with immune functions. The findings suggest a shared gene expression pattern in the prefrontal cortex of people with ASD and HD, closely linked to the immune system. These findings will contribute to exploring the biological mechanisms underlying the shared phenotypes of these two diseases from an immunological perspective.

This research is to explore the impacts of irisin on hyperalgesia and behavioral deficits caused by chronic constriction injury (CCI) and the underlying mechanisms. The CCI mice model was used in this study. The experimental mice were assigned into sham, sham + irisin (3 μg/kg), CCI, CCI + irisin (0.1, 1, and 3 μg/kg), and CCI + irisin (3 μg/kg) + ML385 (30 mg/kg) groups. The results showed that after CCI injury, the mice exhibited hyperalgesia, depression, and anxiety. In addition, the levels of inflammatory cytokines NF-κB, IL-1β, IL-6, TNF-α, and iNOS increased in the mice hippocampus, frontal cortex, and spinal cord. Moreover, oxidative stress relevant factor MDA increased, while GSH and SOD decreased in the mice hippocampus, frontal cortex, and spinal cord. However, irisin treatment ameliorated CCI-induced mechanical allodynia, thermal hyperalgesia, depressive, and anxiety behaviors, and reversed the abnormal expressions of inflammatory and oxidative stress relevant cytokines. Interestingly, these therapeutic effects of irisin were partly abolished by ML385, a specific Nrf2 antagonist. Taken together, irisin may be an effective therapeutic agent for CCI-induced neuralgia and the affective disorders, and the mechanisms may be associated with the anti-neuroinflammation mediated by NF-κB and the anti- oxidative stress function regulated by Nrf2.

The establishment of Russian neurology in the late 19th century was significantly shaped by the neurology department at La Salpêtrière Hospital under Professor Jean-Martin Charcot's leadership. A group of Russian neurologists, guided by Professor Kozhevnikov and featuring his disciples such as Korsakov, Minor, Darkshevich, and Bekhterev, had the privilege of being mentored by Professor Charcot. Subsequently, they played pivotal roles in founding various neurology services in Russia, greatly influenced by the teachings and insights they acquired under Charcot's tutelage.

Introduction: About 15–20 % of babies that suffer perinatal asphyxia die and around 25 % of the survivors exhibit permanent neural outcomes. Minimization of this global health problem has been warranted. This study investigated if the offspring of pregnant female rats allowed to spontaneously exercise on running wheels along a 11-day pregnancy period were protected for somatic and neurodevelopmental disturbs that usually follow neonatal anoxia. Methods: spontaneous exercise was applied to female rats which were housed in cages allowing free access to running wheels along a 11-day pregnancy period. Their offspring were submitted to anoxia 24–36 h after birth. Somatic and sensory-motor development of the pups were recorded until postnatal day 21 (P21). Myelin basic protein (MBP)-stained areas of sensory and motor cortices were measured at P21. Neuronal nuclei (NeuN)-immunopositive cells and synapsin-I levels in hippocampal formation were estimated at P21 and P75. Results: gestational exercise and / or neonatal anoxia increased the weight and the size of the pups. In addition, gestational exercise accelerated somatic and sensory-motor development of the pups and protected them against neonatal-anoxia-induced delay in development. Further, neonatal anoxia reduced MBP stained area in the secondary motor cortex and decreased hippocampal neuronal estimates and synapsin-I levels at P21; gestational exercise prevented these effects. Therefore, spontaneous exercise along pregnancy is a valuable strategy to prevent neonatal-anoxia-induced disturbs in the offspring. Conclusion: spontaneous gestational running wheel exercise protects against neonatal anoxia-induced disturbs in the offspring, including (1) physical and neurobehavioral developmental impairments, and (2) hippocampal and cortical changes. Thus, spontaneous exercise during pregnancy may represent a valuable strategy to prevent disturbs which usually follow neonatal anoxia.

Fluid intelligence is an individual's innate ability to cope with complex situations and is gradually reduced across adults aging. The realization of fluid intelligence requires the simultaneous activity of multiple brain regions and depends on the structural connection of distributed brain regions. Uncovering the structural features of brain connections associated with fluid intelligence decline will provide reference for the development of intervention and treatment programs for cognitive decline. Using structural magnetic resonance imaging data of 454 healthy participants (18–87 years) from the Cam-CAN dataset, we constructed structural similarity network for each participant and calculated the node degree. Spearman correlation analysis showed that age was positively correlated with degree centrality in the cingulate cortex, left insula and subcortical regions, while negatively correlated with that in the orbito-frontal cortex, right middle temporal and precentral regions. Partial least squares (PLS) regression showed that the first PLS components explained 32 % (second PLS component: 20 %, pperm < 0.001) of the variance in fluid intelligence. Additionally, the degree centralities of anterior insula, supplementary motor area, prefrontal, orbito-frontal and anterior cingulate cortices, which are critical nodes of the multiple-demand network (MDN), were linked to fluid intelligence. Increased degree centrality in anterior cingulate cortex and left insula partially mediated age-related decline in fluid intelligence. Collectively, these findings suggest that the structural stability of MDN might contribute to the maintenance of fluid intelligence.

Aims: This study is to investigate the effects of Cannabinoid type 2 receptor (CB2R) deficiency on microglia and cognitive function in both Aβ1–42-injected CB2R knockout mice and a transgenic mouse model of Alzheimer’s disease (AD) in brain. Methods: After hippocampal injection with Aβ1–42 oligomers in CB2R knockout mice with and without CB2R agonist treatment and in transgenic APP/PS1 mice with CB2R deletion, the novel object recognition (NOR) and Morris water maze (MWM) tests were performed to assess the animal behavior performance. Immunofluorescence staining was conducted to detect the microglial morphology and activation status. The expression of proinflammation and anti-inflammation cytokines were determined by qRT-PCR. Results: CB2R deficiency significantly aggravated cognitive impairment in both Aβ1–42-induced and transgenic APP/PS1 animal model in NOR. In Aβ-injected mice lacking CB2R and transgenic APP/PS1 mice with CB2R deletion, microglia in the prefrontal cortex exhibited enhanced immunoreactivity with altered morphology. Furthermore, transformation of activated microglial phenotype in the prefrontal cortex was reduced in Aβ1–42-injected CB2R knockout mice after CB2R agonist treatment. The CB2R deficiency significantly increased the expression of proinflammatory cytokines in the prefrontal cortex, while it was observed in the hippocampus in both Aβ1–42-injected and transgenic APP/PS1 AD mouse model. Furthermore, CB2R deficiency increased concentrations of soluble Aβ 40 in the prefrontal cortex, but did not affect plaques deposition. Conclusion: CB2R deletion led to enhanced neuroinflammatory responses via direct upregulating microglia activation in the prefrontal cortex during the early symptomatic phase of AD mice. CB2R modulates prefrontal cortical neuroinflammation, which is essential for regulating cognitive functions such as recognition memory at the early stage of AD.

Postnatal neurogenesis appears to be highly sensitive to environmental factors, including microwave electromagnetic radiation (MWR). Here, we investigated the impact of MWR during intrauterine development on juvenile and adult neurogenesis in the rostral migratory stream (RMS) and the dentate gyrus of the hippocampus in the rat brain, as well as its effect on animal behavior. Female rats were exposed to MWR at a frequency of 2.45 GHz for 2 hours daily throughout pregnancy. The offspring of irradiated mothers survived to either juvenile age or adulthood. The brains of the rats were subjected to morphological analysis, assessing cell proliferation and death in both neurogenic regions. In the RMS, the differentiation of nitrergic neurons was also investigated. The effect of MWR on behavior was evaluated in rats surviving to adulthood. Prenatal MWR exposure caused significant changes in the number of proliferating and dying cells, depending on the age of the animals and the observed neurogenic region. In addition, MWR attenuated the maturation of nitrergic neurons in the RMS in both juvenile and adult rats. Morphological alterations in neurogenesis were accompanied by changes in animals’ behavior. Affected neurogenesis and changes in animal behavior suggest a high sensitivity of the developing brain to MWR.

Background: Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by dopamine depletion and severe motor impairments. Preladenant, an adenosine A2 receptor antagonist, is an investigational treatment for PD. This systematic review and meta-analysis aimed to critically evaluate the efficacy of Preladenant in improving motor symptoms in patients with PD. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to March 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing Preladenant with placebo in PD patients were included. The primary outcome was the change in daily ON time without troublesome dyskinesia. Secondary outcomes included the change in daily OFF time and adverse events. The risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Four RCTs with a total of 2097 PD patients were included. Pooled analysis showed that Preladenant could generally increase daily ON time (pooled effect 0.15 and 95 % CI: −0.19–0.48) and reduce daily OFF time (pooled effect −0.04 and 95 % CI: −0.43–0.36) compared to placebo, however it was not significant. The included studies had moderate to high heterogeneity. No significant differences in adverse events were observed between Preladenant and placebo. Conclusion: This meta-analysis suggests that Preladenant may improve motor fluctuations in PD patients by increasing ON time and reducing OFF time. However, the high heterogeneity among studies warrants further large-scale, high-quality RCTs to confirm these findings and establish the long-term safety and efficacy of Preladenant in PD management.

The Antisecretory Factor (AF) is a protein that can reduce intestinal hypersecretion and various inflammation disorders in vivo. Discovered in many mammalian tissues and plasma, its mechanism of action remains unknown. Interestingly, its induction has been found to counteract vertigo in patients with Méniere's disease. This suggests an inherent ability to control body balance and posture, an activity that may play a role in cerebellar function. Therefore, it may be worthwhile to investigate whether this activity can inhibit neuronal cells involved in cerebellar circuitries and its potential action on enteric nervous system ganglia, which could explain its antisecretory effect in the intestine.Previously, we studied the role of AF on GABAA receptors in cerebellar granule cells, taking advantage of electrophysiology and evaluating the effects of the administration of AF-16, an AF peptide. Treatment with AF-16 increased GABAA receptor responses, especially those containing the α6 subunit. Here, we performed immunofluorescence experiments by staining α1 and α6 subunits before and after incubation with AF-16, analyzed super-resolved images comparing pre- and post-treatment maps and critically examined these experimental results with our previous electrophysiological data to shed light on the mechanisms of action of AF protein on GABAA receptor subpopulations, specifically the ''fast'' receptors of αn β2/3 γ2 composition that contain either the α1 or the α6 subunit.The results indicate that the α6 subunit is redistributed, with a decrease in neurites and an increase in soma. Conversely, the α1 subunit shows opposite results, with an increase in neurites and a decrease in soma.

Interleukin-33 (IL-33) is a member of the interleukin-1 cytokine family. Its function in regulating microglial M1/M2 polarization in neuromyelitis optica spectrum disorder (NMOSD) is still unelucidated. To evaluate the role of IL-33 in NMOSD, we constructed NMOSD mice model by injecting purified serum IgG from AQP4-IgG seropositive NMOSD patients into experimental autoimmune encephalomyelitis (EAE) mice, and IL-33 was intraperitoneally injected into NMOSD mice 3 d before the model induction. We found that pretreatment of the NMOSD mice with IL-33 relieved brain neuron loss, and demyelination and improved the structure of axons, astrocytes, and mitochondria. In the neuronal and microglial coculture system, pretreatment with IL-33 in microglia alleviated NMOSD serum-induced inflammation and damaged morphology in cultured neurons. IL-33 transformed microglia to the M2 phenotype, and NMOSD serum promoted microglia to the M1 phenotype in cultured BV2 cells. Moreover, IL-33 influenced microglial polarity via the IL-33/ST2 pathway. IL-33 may be a novel insight useful for further developing NMOSD-targeted therapy and drug development.

Background: Following recent research advancements, an increasing level of evidence had been published to indicate that celastrol exerted a therapeutic effect on a range of nervous system diseases. This study therefore aimed to investigate the potential involvement of celastrol on ferroptosis and the blood-brain barrier disruption in intracerebral haemorrhage. Methods: We established a rat intracerebral haemorrhage and adrenal pheochromocytoma cell (PC12) OxyHb models using an ACSL4 overexpression vector. Ferroptosis-related indices were assessed using corresponding assay kits, and immunofluorescence and flow cytometry were used to measure reactive oxygen species (ROS) levels. Additionally, quantitative PCR (qPCR) and western blot analyses were conducted to evaluate the expression of key proteins and elucidate the role of celastrol in intracerebral haemorrhage (ICH). Results: Celastrol significantly improved neurological function scores, blood-brain barrier integrity, and brain water content in rats with ICH. Moreover, subsequent analysis of ferroptosis-related markers, such as Fe2+, ROS, MDA, and SOD, suggested that celastrol exerted a protective effect against the oxidative damage induced by ferroptosis in ICH rats and cells. Furthermore, Western blotting indicated that celastrol attenuated ferroptosis by modulating the expression levels of key proteins, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and anti-transferrin receptor 1 (TFR1) both in vitro and in vivo. ACSL4 overexpression attenuated the neuroprotective effects of celastrol on ICH in vitro. Molecular docking analysis revealed that celastrol interacted with ACSL4 via the GLU107, GLN109, ASN111, and LYS357 binding sites. Conclusions: Celastrol exerted antioxidant properties and aids in neurological recovery after stroke by suppressing ACSL4 expression during ferroptosis. As such, this drug represented a promising pharmaceutical candidate for the treatment of ICH.

Middle cerebral artery occlusion (MCAO) is a model for inducing ischemic stroke in rodents, leading to devastating brain damage. Oxidative stress (OS) plays a crucial role in the pathogenesis of ischemia. In this study, the effect of melatonin and N-acetylcysteine on ischemia-reperfusion-induced oxidative stress injury in the cerebral cortex of male rats was investigated. 30 male Wistar rats were divided into sham, ischemic, NAC, melatonin and NAC + melatonin groups. All groups, except the sham group, underwent MCAO on the left side, and the treatment groups received intraperitoneal injections of either 50 mg/kg N-acetylcysteine (NAC) or 5 mg/kg melatonin or a combination of both 24 and 48 hours later. At 24 and 72 hours after surgery, the animals were examined for sensory and motor activity. The cerebral cortex was dissected after sacrificing the rats, infarct volume estimated and the concentrations of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nuclear factor erythroid-2 related factor 2 (Nrf2) were analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicate that the NAC + melatonin group exhibited elevated sensory-motor activity and a reduced infarct volume rate in comparison to the ischemic group (p≤ 0.05). Compared to the ischemic group, the NAC + melatonin group showed a significant increase in SOD concentration and a significant decrease in MDA (p≤ 0.05). It can therefore be concluded that the simultaneous administration of NAC and melatonin can reduce the cerebral infarction volume, and improve neurological functions by modulating SOD and MDA.

Optomotor responses are a popular way to assess sub-cortical visual responses in mice. We studied photoreceptor inputs into optomotor circuits using genetically-modified mice lacking the exocytotic calcium sensors synaptotagmin 1 (Syt1) and 7 (Syt7) in rods or cones. We also tested mice that in which cone transducin, GNAT2, had been eliminated. We studied spatial frequency sensitivity under mesopic conditions by varying the spatial frequency of a grating rotating at 12 deg/s and contrast sensitivity by varying luminance contrast of 0.2c/deg gratings. We found that eliminating Syt1 from rods reduced responses to a low spatial frequency grating (0.05c/deg) consistent with low resolution in this pathway. Conversely, eliminating the ability of cones to respond to light (by eliminating GNAT2) or transmit light responses (by selectively eliminating Syt1) showed weaker responses to a high spatial frequency grating (3c/deg). Eliminating Syt7 from the entire optomotor pathway in a global knockout had no significant effect on optomotor responses. We isolated the secondary rod pathway involving transmission of rod responses to cones via gap junctions by simultaneously eliminating Syt1 from rods and GNAT2 from cones. We found that the secondary rod pathway is sufficient to drive robust optomotor responses under mesopic conditions. Finally, eliminating Syt1 from both rods and cones almost completely abolished optomotor responses, but we detected weak responses to large, bright rotating gratings that are likely driven by input from intrinsically photosensitive retinal ganglion cells.

Purpose: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. Methods: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ1–42/Aβ1–40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. Results: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P

Salix mucronata is one of the herbal plants offered by the traditional health practitioners in KwaZulu-Natal, South Africa for the treatment of schizophrenia. This study aimed to investigate the effects of repeated administration of ketamine on social interaction, novelty and motivation in adult, male Sprague Dawley rats. It also aimed to investigate the potential of risperidone and the herbal extract of S. mucronata to reverse impairments that are induced by ketamine. Experimental rats (n=45) received a dose of ketamine at 30 mg/kg via intraperitoneal injection for 5 consecutive days. They were then allocated into their respective treatment groups and given risperidone (APD) and the herbal extract of S. mucronata (TM) at doses of 6 mg/kg and 5 mg/kg, respectively, for 7 consecutive days. Social behaviour was tested using the 3-chambered sociability test, and anhedonia was tested using the sucrose preference test. Ketamine induction elicited social withdrawal and reduced social novelty which were later successfully reversed by risperidone and S. mucronata. The rats showed reduced preference to sucrose post-induction and post-treatment. Ketamine and mild stress caused by scruff restraint elicited reduced weight gain for the animals. No differences were noted on brain mass between controls and experimental groups and also between risperidone and S. mucronata groups. However, reduced brain volume was noted in experimental groups. Dopamine and acetylcholine concentration levels were high in groups which received risperidone and S. mucronata. These findings highlight that the antipsychotic potential of S. mucronata is similar to risperidone.

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians’ awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.

About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were unresponsive to the antidepressant-like effects induced by the tricyclic antidepressant imipramine and the selective serotonin reuptake inhibitor fluoxetine. However, acute pharmacological inhibition of PI3Kγ did not block the antidepressant-like effect of ketamine, showing that a chronic deficiency of the PI3Kγ-mediated pathway is necessary for the effects of classic doses of ketamine and antidepressants. Therefore, we propose that PI3Kγ participates in the antidepressant activity and is likely implicated in the neurobiology and phenotype observed in patients with MDD who demonstrate treatment resistance.

Neuroblastomas are pediatric tumors arising from undifferentiated cells of neural crest origin with stem cell-like characteristics. Dysregulation of Wnt/β-catenin signaling has been shown to be linked to the development of various tumors. Activated Wnt signaling results in β-catenin accumulation in the nucleus to support pro-neoplastic traits. DKK1, a secreted glycoprotein, is an inhibitor of Wnt signaling, and the addition of DKKI to the culture medium has been used to suppress the Wnt pathway. This study aimed to analyze the role of Dickopff-1 as a potential differentiating agent for the neuroblastoma cell line SH-SY5Y and neurospheres derived from it. The treatment of SH-5Y5Y derived neurospheres by DKK1 resulted in their disintegration and reduced proliferation markers like Ki67, PCNA. DKK1 treatment to the neurospheres also resulted in the loss of cancer stem cell markers like CD133, KIT and pluripotency markers like SOX2, OCT4, NANOG. DKK1 treatment caused reduction in mRNA expression of β-catenin and TCF genes like TCF4, TCF12. When the SH-SY5Y cancer cells were grown under differentiating conditions, DKKI caused neuronal differentiation by itself, and in synergy with retinoic acid. This was verified by the expression of markers like MAPT, DCX, GAP43, ENO2 and also with changes in neurite length. We concluded that Wnt inhibition, as exemplified by DKK1 treatment, is therefore a possible differentiating condition and also suppresses the proliferative and cancer stemness related properties of SH-SY5Y neuroblastoma cells.

Lead (Pb) is a ubiquitous, non-biodegradable heavy metal contaminant with a significant impact on both human and animal health. The adverse effect of lead on health and productivity of avian species has received little attention. Alchornea laxiflora (Benth) belongs to Euphorbiaceae family and grows naturally in the Nigerian rain forest. Decoction of the leaves is usually administered traditionally to treat inflammatory and infectious diseases. The ethanol extract of Alchornea laxiflora (EaAL) leaves was used in this study to ameliorate lead-induced neurodegeneration.Seven groups of 5-week-old cockerels (n=5) were treated for 6 weeks thus: Group A - Control (water only), Group B - (100 mg/kg of EaAL daily), Group C - (200 mg/kg of EaAL daily, p.o.), Group D - (1 % lead acetate in drinking water), Group E - (1 % lead acetate in drinking water and 100 mg/kg of EaAL daily), Group F - (1 % lead acetate and 200 mg/kg of EaAL daily), Group G - (1 % lead acetate and 100 mg/kg of Vitamin C). All administrations were per os birds were euthanized on day 43 by quick cervical dislocation. Histological stains (H&E and Nissl) and Black Gold II (BGII) histochemistry were used to assess alterations in the cerebrum and cerebellum.Administration of EaAL at the two concentrations resulted in a drastic reduction in the incidence of neuropathologies observed (e.g. pyknosis and multilayering of Purkinje cells, neuronal degeneration in hippocampus cerebrum and ependymal cells, distortion of meningeal epithelial cells, etc). BGII histochemistry revealed severe demyelination caused by the administration of lead acetate, while the two doses of EaAL showed significant restoration of myelin in the cerebellum. The amelioration of demyelination observed with the use of vitamin C was considerably lower than that recorded with the use of EaAL.The use of EaAL significantly ameliorated morphological alterations and demyelination caused by the administration of lead acetate, however, caution should be exercised in the administration, as individual species idiosyncrasies may arise and the tendency to pro-oxidation at 200 mg/kg when administered alone was observed in one subject.

Previous investigations have revealed the role of GABAergic and serotonergic systems in the modulation of pain behavior. This research aimed to examine the effects of intracerebroventricular (i.c.v.) infusion of GABAA receptor agonist and antagonist as well as citalopram on pain behavior in male mice. For i.c.v. microinjection, a guide cannula was surgically implanted in the left lateral ventricle of male mice. Pain behavior was evaluated using a tail-flick test. Tail flick latency was measured in each experimental group of mice every 15 min (for 60 min). I.c.v. microinjection of muscimol (0.5 and 1 µg/mouse; GABAA receptor agonist) into the left lateral ventricle dose-dependently induced an antinociceptive effect. On the other hand, i.c.v. infusion of bicuculline (1 µg/mouse; GABAA receptor antagonist) induced a hyperalgesia response. Moreover, intraperitoneally (i.p.) administration of citalopram (8 mg/kg) produced an antinociceptive effect. Co-treatment of citalopram (8 mg/kg) along with muscimol (0.25 µg/mouse) or bicuculline (0.25 µg/mouse) potentiated the antinociceptive effect produced by citalopram. We found an additive antinociceptive effect of citalopram and muscimol in male mice. In conclusion, our results suggested an interaction between citalopram and GABAergic agents on the modulation of pain behavior in male mice.

First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. Csf3r and Fkbp5). Some, e.g. Alox15 and Slc12a5, were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.

Previous studies have demonstrated an increasing trend of the number of authors across various fields over the years. This trend has been attributed to the necessity for larger collaborations and, at times, to ethical issues regarding authorship attribution. Our study focuses on the evolution of authorship trends in the field of Neuroscience. We conducted our analysis based on a dataset containing 580,782 neuroscience publications produced from 2000 to 2022, focusing on the publications within the Group of ten (G10) countries. Using a matrix-based methodology, we extracted and analyzed the average number of authors per country. Our findings reveal a consistent rise in authorship across all G10 countries over the past two decades. Italy emerged with the highest average number of authors, while France stood out for experiencing the most significant increase, particularly in the last decade. The countries with the lowest number of authors per publication were the USA, UK and Canada. Differences between countries could result from variations in the size of collaboration between researchers in different countries. Additionally, these differences may depend on utilitarian considerations aimed at receiving higher scores in the individual evaluation of their own work. We propose that a normalization procedure for the number of authors should be implemented to ensure a fair evaluation of researchers.

Visual errors induced by movement drive implicit corrections of that movement. When similar errors are experienced consecutively, does sensitivity to the error remain consistent each time? This study aimed to investigate the modulation of implicit error sensitivity through continuous exposure to the same errors. In the reaching task using visual error-clamp feedback, participants were presented with the same error in direction and magnitude for four consecutive trials. We found that implicit error sensitivity decreased after exposure to the second error. These results indicate that when visual errors occur consecutively, the sensorimotor system exhibits different responses, even for identical errors. The continuity of errors may be a factor that modulates error sensitivity.

Concussions sustained while playing sports are a prominent cause of mild traumatic brain injury (mTBI), which is prevalent among teenagers. The early and intermediate stages of mild traumatic brain injury (mTBI) can be characterized by inflammation, neurodegeneration, and brain tissue edema, which can lead to permanent brain damage.The present study investigated the therapeutic effects of triptolide in mTBI and brain damage recovery. After building mTBI model in male rat, triptolide administrated daily for 1 week in the treated group. On day 3 and day 7 of administration, hippocampus tissues were collected to evaluate inflammation and autophagy in the brain. The expressions of inflammatory factors interleukin (IL)-1β and tumor necrosis factor-alpha in serum were downregulated, while IL-10 expression was upregulated when compared with the mTBI group on day 3 and day 7. The expression of IL-10 on day 7 was higher than on day 3. Quantitative polymerase chain reaction (qPCR) analysis of inflammatory-related factors (i.e., Il-1β and nuclear factor-κB (Nf-κb), and western blot as well as immunofluorescence staining of autophagy-related proteins (i.e., LC3B) and aquaporin (AQP 4) showed lower expression on day 3 and day 7 in the triptolide-treated group. Moreover, NeuN immunostaining, and hematoxylin and eosin (HE) staining for hippocampus region revealed that the triptolide-treated group showed a decrease in damaged cells. Our findings emphasize the effectiveness of triptolide therapy after mild traumatic brain injury via modulating autophagy, attenuating inflammation and reduces edema by decreasing AQP 4 expression.

Symmetry breaking leading to axis formation and spatial patterning is crucial for achieving more accurate recapitulation of human development in organoids. While these processes can occur spontaneously by self-organizing capabilities of pluripotent stem cells, they can often result in variation in structure and composition of cell types within organoids. To address this limitation, bioengineering techniques that utilize geometric, topological and stiffness factors are increasingly employed to enhance control and consistency. Here, we review how spontaneous manners and engineering tools such as micropattern, microfluidics, biomaterials, etc. can facilitate the process of symmetry breaking leading to germ layer patterning and the formation of anteroposterior and dorsoventral axes in blastoids, gastruloids, neuruloids and neural organoids. Furthermore, brain assembloids, which are composed of multiple brain regions through fusion processes are discussed. The overview of organoid polarization in terms of patterning tools can offer valuable insights for enhancing the physiological relevance of organoid system.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Death of dopaminergic cells in the SNpc leads to manifestations of motor dysfunction and non-motor symptoms of PD. The progression of PD symptoms severely affects the quality of life of patients and poses socio-economic problems to families and society at large. The clinical and neuropathological characteristics of PD are triggered by multiple factors such as oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein aggregation. Notwithstanding the advancements in pharmacological therapy in PD management, there is burgeoning interest in alternative and complementary approaches, essentially nutrition and plant extracts strategies. This review gives widespread analysis of the role of nutrition and plant extracts in the management of PD. Studies that investigated the effects of various dietary compounds and plant extract on PD symptoms and progression were reviewed from existing literatures. Nutraceuticals, including vitamins and phytochemicals such as Mucuna pruriens have shown potential neuroprotective functions in preclinical and clinical studies. Indeed, these strategies ameliorate mitochondrial dysfunction, oxidative stress, and neuroinflammation, all which are implicated in the pathogenesis of PD. The neuroprotective mechanisms of nutrition and plant extracts in PD, with emphasis on their capacity to target multiple pathways implicated in PD are discussed. Additionally, challenges and limitations related with translating preclinical findings into clinical practice including standardization of dosing regimens, bioavailability, and inter-individual variability are discussed. Largely, this review elucidates on the role of nutrition and plant extracts as adjunctive therapy in PD management.

Abstract Background Lithium is our oldest continuously prescribed medication in psychopharmacology, with its history as an agent for treating mood disorders extending from the 19th century. Although clinicians prescribe it less frequently than in the past, its utility in treating bipolar disorder is unquestionable. Novel potential indications for its use in psychiatry have created excitement about broader roles for lithium in treating and preventing other disorders. Content Lithium is effective both in treating acute mania, as an adjunctive antidepressant, and as a maintenance treatment in bipolar disorder. Lithium has also shown some efficacy in treating and preventing unipolar depression, but less clearly than for bipolar maintenance treatment and acute mania. Common side effects include nausea, polyuria, tremor, weight gain and cognitive dulling. These side effects are typically manageable with reasonable clinical strategies. Lithium affects renal, thyroid and parathyroid function. With clinical monitoring, these effects are easily managed although infrequent cases of severe renal insufficiency may occur with long term use. Although not all studies are positive, a consistent database suggests the efficacy of lithium in decreasing suicide attempts and suicides, likely due to its effect on impulsivity and aggression as well as its prophylaxis against depressive and manic recurrences. Recent data have suggested lithium’s potential efficacy for a number of new clinical indications. Lithium’s neuroprotective effects suggest potential efficacy in preventing mild cognitive impairment (MCI) and dementia as well as in aiding recovery from strokes. Higher (but still trace) lithium levels in drinking water are associated with lower rates of dementia. It is still not clear how much lithium-and what serum lithium levels- are required for either of these effects. Other preliminary research suggests that lithium may also have antiviral effects and may decrease cancer risk. Conclusions Lithium continues to be the mainstay treatment of mood disorders in general and in bipolar disorder specifically. Other potential clinical uses for lithium in psychiatry have re-invigorated excitement for research in other areas such as suicide, preventing cognitive impairment and possibly preventing viral infections and diminishing cancer risk.

Abstract Background Cognitive impairment is frequently observed in bipolar disorder (BD). Previous findings indicated that predominant polarity could have an effect on cognitive deficits. This study aimed to examine the association between predominant polarity and cognitive impairments in BD. Materials and methods Euthymic BD patients with manic (MPP, n = 31), depressive (DPP, n = 25), undetermined predominant polarity (UPP, n = 28), and healthy controls (HC, n = 27) participated in the study. A battery of neurocognitive and social cognitive tests was implemented. Neurocognitive domains were identified via principal component analysis. Results The MPP group performed worse in the Controlled Oral Word Association Test (COWAT), Reading the Mind in the Eyes Test (RMET), and Hinting Test (HT) compared to the DPP group and reasoning/problem-solving skills compared to the UPP group. Both MPP and UPP groups showed impairments in processing speed compared to HC. Among patient groups, there was no significant difference in working memory, attention, processing speed, verbal, and visual domain scores. The MPP group had poorer scores compared to controls in most of the social cognitive and neurocognitive domains in the study, while the overall cognitive impairment in the DPP group was relatively milder. Conclusions Although our sample size was relatively small, the MPP group yielded more severe cognitive impairment in verbal fluency and social cognition tests compared to DPP. Patients with MPP are particularly vulnerable to cognitive impairment, making them a priority for cognitive enhancement interventions. Future studies should focus on the outcomes of cognitive and pharmacological interventions in these polarity subgroups.

Abstract Background Mutations in the X-linked CDKL5 gene underlie a severe epileptic encephalopathy, CDKL5 deficiency disorder (CDD), characterized by gross motor impairment, autistic features and intellectual disability. Absence of Cdkl5 negatively impacts neuronal proliferation, survival, and maturation in in vitro and in vivo models, resulting in behavioral deficits in the Cdkl5 KO mouse. While there is no targeted therapy for CDD, several studies showed that treatments enabling an increase in brain BDNF levels give rise to structural and behavioral improvements in Cdkl5 KO mice. P021, a tetra-peptide derived from the biologically active region of the human ciliary neurotrophic factor (CNTF), was found to enhance neurogenesis and synaptic plasticity by promoting an increase in BDNF expression in preclinical models of brain disorders, such as Alzheimer’s disease and Down syndrome, resulting in a beneficial therapeutic effect. Considering the positive actions of P021 on brain development and cognition associated with increased BDNF expression, the present study aimed to evaluate the possible beneficial effect of treatment with P021 in an in vitro and in vivo model of CDD. Methods We used SH-CDKL5-KO cells as an in vitro model of CDD to test the efficacy of P021 on neuronal proliferation, survival, and maturation. In addition, both young and adult Cdkl5 KO mice were used to evaluate the in vivo effects of P021, on neuroanatomical and behavioral defects. Results We found that P021 treatment was effective in restoring neuronal proliferation, survival, and maturation deficits, as well as alterations in the GSK3β signaling pathway, features that characterize a human neuronal model of CDKL5 deficiency. Unexpectedly, chronic in vivo P021 treatment failed to increase BDNF levels and did not improve neuroanatomical defects in Cdkl5 KO mice, resulting in limited behavioral benefit. Conclusions At present, it remains to be understood whether initiating the treatment prenatally, or prolonging the duration of treatment will be necessary in order to achieve similar results in vivo in CDD mice to those obtained in vitro.

Abstract This report presents results of parent-implemented behavioral treatments for a child with cortical visual impairment (CVI), intellectual disability (ID), epilepsy, and autism spectrum disorder (ASD) associated with a pathogenic variant in the SCN2A gene (i.e., SCN2A-Related Disorder). Treatment evaluations were informed by combined results of functional behavior assessment (FBA) and functional vision assessment (FVA) which yielded CVI-related accommodations. The treatment of escape-maintained challenging behavior involved the evaluation of behavioral prompting strategies in accordance with CVI-related accommodations, extinction (EXT), and differential reinforcement modifications. The treatment for behavior problems maintained by access to food (tangible-edible) included functional communication training (FCT), EXT, and schedule thinning with schedule-correlated visual signals. Overall, integrating child-specific CVI-related accommodations was essential for developing effective behavioral interventions for this child. FVAs are accessible and practical for uptake by behavior analysts in vision-informed assessment and treatment of challenging behavior.

Abstract Procedural learning and automatization have widely been studied in behavioral psychology and typically involves a rapid improvement, followed by a plateau in performance throughout repeated training. More recently, brain imaging studies have implicated frontal-striatal brain circuits in skill learning. However, it is largely unknown whether frontal-striatal activation during skill learning and behavioral changes follow a similar learning curve pattern. To address this gap in knowledge, we performed a longitudinal brain imaging study using a procedural working memory (pWM) task with repeated measurements across two weeks to map the temporal dynamics of skill learning. We additionally explored the effect of the BDNF Val 66 Met polymorphism, a common genetic polymorphism impacting neural plasticity, to further inform the relevance of the identified neural markers. We used linear and exponential modeling to characterize procedural learning by means of learning curves on the behavioral and brain functional level. We show that repeated training led to an exponential decay in a distributed set of brain regions including fronto-striatal circuits, which paralleled the exponential improvement in task performance. In addition, we show that both behavioral and neurofunctional readouts were sensitive to the BDNF Val 66 Met polymorphism, suggesting less efficient learning in 66 Met-allele carriers along with protracted signal decay in frontal and striatal brain regions. Our results extend existing literature by showing the temporal relationship between procedural learning and frontal-striatal brain function and suggest a role of BDNF in mediating neural plasticity for establishing automatized behavior.

Abstract Healthy aging often entails a decline in cognitive and motor functions, affecting independence and quality of life in older adults. Brain stimulation shows potential to enhance these functions, but studies show variable effects. Previous studies have tried to identify responders and non-responders through correlations between behavioral change and baseline parameters, but results lack generalization to independent cohorts. We propose a method to predict an individual’s likelihood of benefiting from stimulation, based on baseline performance of a sequential motor task. Our results show that individuals with less efficient learning mechanisms benefit from stimulation, while those with optimal learning strategies experience none or even detrimental effects. This differential effect, first identified in a public dataset and replicated here in an independent cohort, was linked to one’s ability to integrate task-relevant information and not age. This study constitutes a further step towards personalized clinical-translational interventions based on brain stimulation.

Abstract Using register data and linked student-level sociometric survey data from the Netherlands, this study examines whether the impact of the COVID-19 pandemic on schooling outcomes (track recommendation and track enrollment in the seventh and ninth grades) is conditional on students’ academic and social embeddedness in the school setting. We estimated the counterfactual outcomes for the cohort that went through the school transition during the pandemic based on the outcomes of the pre-pandemic cohort, with similar earlier achievements, schools, and social backgrounds. Results show that the pandemic’s effect on tracking outcomes is weaker than its effect on student test scores elsewhere reported. Nevertheless, the pandemic has had stronger adverse impact on disadvantaged students. Moreover, student self-efficacy, academic motivation, and parental involvement are related to more negligible negative pandemic effects on schooling outcomes. We find no evidence for an association between student grit or parental network centrality and the magnitude of estimated pandemic effects.

Abstract Purpose Lung injury associated with bronchopulmonary dysplasia (BPD) and its related neurodevelopmental disorders have garnered increasing attention in the context of premature infants. Establishing a reliable animal model is essential for delving into the underlying mechanisms of these conditions. Methods Newborn rats were randomly assigned to two groups: the hyperoxia-induced BPD group and the normoxia (NO) group. For the BPD group, they were nurtured in a hyperoxic environment with a high oxygen inspired fraction (0.85) from birth until day 14 within 28 days postnatally. In contrast, the NO group consisted of newborn rats that were nurtured in a normoxic environment with a standard oxygen inspired fraction (0.21) for 28 days postnatally. Various pathological sections of both lung and brain tissues were examined. TUNEL staining, immunofluorescence assays, and functional tests were performed, and the results were meticulously analyzed to assess the impact of hyperoxia environments on the developing organs. Results In the newborn rats of the BPD group, a significant reduction in alveolar number coupled with enlargement was observed, alongside severe fibrosis, collagen deposition, and constriction of bronchi and vascular lumens. This was accompanied by an accumulation of inflammatory cells and a marked deterioration in lung function compared to the NO group (P

Abstract Introduction The prevalence of important public health problems like road traffic accidents (RTA) and depression are surging. This study was aimed to estimate distribution and determine the association between RTA and depression among Indian population aged 45 years and above: overall and stratified into age group, gender and across states/union territories as aspirants, achievers, and front runners. Methods Using Longitudinal Aging Study in India (LASI) dataset (April 2017–December 2018), we have conducted this study among middle aged (45–59 years) and older adults and elderly (≥ 60 years) Indians. Bivariate analysis was conducted to estimate the prevalence of RTA and depression nationally and across aspirants, achievers, and front runner states. States and union territories were categorised as low, medium, and high as per RTA and depression prevalence, which were further cross tabulated. Spatial distribution maps were created using Microsoft Excel. We have documented the association of RTA with depression. To reduce the confounding effects of demographic and socioeconomic; health related and behavioural covariates; propensity score matching (PSM) was conducted. Nested multilevel regression modelling was analysed using STATA version 17. Results Prevalence of RTA was 1.84% (1.74–1.94) nationally, highest among achiever states [2.04% (1.82–2.30)]. Prevalence of depression was 6.08% (5.90–6.26) nationally, highest among aspirant states [7.02% (6.74–7.30)]. The adjusted odds of having RTA was significantly among depressed [aOR (95% CI) 1.76 (1.45–2.15)] than non-depressed participants; which was much higher among females [aOR (95% CI) 1.93 (1.43–2.62)] than in males [aOR (95%CI) 1.67 (1.29–2.16)] and much higher among middle aged [aOR (95%CI) 2.08 (1.63–2.65)]. Odds of RTA was highest across front runners [aOR (95%CI) 1.86 (1.26–2.72)] followed by aspirant states [aOR (95%CI) 1.79 (1.37–2.33)]. Conclusion This study established the positive association between depression and road traffic accidents among middle aged, older adults and elderly. Therefore, efforts must be taken to address mental health issues in them with proper policy implication more focused on females and middle aged. Front runner’s states should get the limelight followed by aspirant states.

Abstract Background Psychological distress is becoming more prominent among employees in various workplaces, and domestic work may not be an exception. This study aimed to determine the prevalence of psychological distress and associated factors among domestic workers in Rwanda. Methods This cross-sectional study captured data from 870 domestic workers in Kigali City, Rwanda. Psychological distress was measured using questions from the Kessler Psychological Distress Scale (K10). Binary Logistic regression analyses were used to ascertain the factors associated with psychological distress. Results The prevalence of psychological distress was 50.1%. The likelihood of having psychological distress was higher among females, those using substances of abuse, those having over four dependents in the household, and those having worked as domestic workers longer. Conclusion Half of the domestic workers in Kigali-Rwanda experience distress. To mitigate this burden, awareness of psychological distress among domestic workers and improvement of services to mitigate psychological distress should be increased. These services should particularly target those who are female, with more dependents, who have worked longer in the profession, and who use substances of addiction.

Abstract We retrospectively reviewed charts of 253 self-harming patients admitted to emergency units in Northern Uganda in 2021. Twenty-two (8.7%) died by suicide, especially due to organophosphate poisoning (n = 14, 63.6%). Regarding self-harm management, observed differences were noted in the type of hospital and the use of antidotes between public and private facilities. There is a need for more studies and a multisector approach to prevent and treat self-harm in Uganda.

Abstract Background We evaluated the feasibility, safety, and efficacy of a 2D-planar robot for minimally supervised home-based upper-limb therapy for post-stroke hemiparesis. Methods The H-Man, end effector robot, combined with web-based software application for remote tele-monitoring were evaluated at homes of participants. Inclusion criteria were: strokes > 28 days, Fugl-Meyer Motor Assessment (FMA) > 10-60/66, presence of a carer and absence of medical contraindications. Participants performed self-directed, minimally supervised robotics-assisted therapy (RAT) at home for 30 consecutive days, after 2 therapist-supervised clinic on-boarding sessions. Web-based compliance measures were: accessed sessions of > 20 min/day, training minutes/day and active training hours/30 days. Clinical outcomes at weeks 0, 5 (post-training), 12 and 24 (follow-up) consisted of FMA, Action Research Arm Test (ARAT) and WHO-Stroke Specific Quality of Life (SSQOL). To estimate immediate economic benefits of the home-based robotic therapy, we performed cost-effectiveness analysis (CEA), followed by budget impact analysis (BIA). Results Altogether, all 12 participants completed Home-RAT without adverse events; 9 (75.0%) were males, mean (SD) age, 59.4 years (9.5), median (IQR) stroke duration 38.6 weeks (25.4, 79.6) baseline FMA (0–66) 42.1 ± 13.2, ARAT (0–57) 25.4 ± 19.5, SSQOL (0–245) 185.3 ± 32.8. At week 5 follow-up, mean (SD) accessed days were 26.3 days ± 6.4, active training hours of 35.3 h ± 14.7/30 days, or ~ 6 days/week and 77 training minutes ± 20.9/day were observed. Significant gains were observed from baseline across time; ΔFMA 2.4 at week 5 (FMA 44.5, CI 95% 39.7–49.3, p

Abstract Background Robot-assisted rehabilitation is considered beneficial for functional recovery in patients with stroke, but the therapeutic effect remains inconclusive. The present study investigated the therapeutic effects of gait training assisted by a user-initiated powered exoskeletal robot (UIPER) in patients in the early stage after stroke. We also characterized patients’ improvement by analyzing chronological changes in clinical measurements together with gait parameters obtained from internal sensors in the exoskeletal robot. Methods In this pilot case-controlled study, 17 and 81 patients with stroke onset durations of

Abstract Background Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are common non-invasive brain stimulation (NIBS) methods for functional recovery after stroke. Motor imagery (MI) can be used in the rehabilitation of limb motor function after stroke, but its effectiveness remains to be rigorously established. Furthermore, there is a growing interest in the combined application of NIBS with MI, yet the evidence regarding its impact on the recovery of upper limb function after stroke is inconclusive. This meta-analysis aimed to demonstrate whether combining the two is superior to NIBS alone or MI alone to provide a reference for clinical decision-making. Methods PubMed, EMBASE, Cochrane Library, Web of Science, Science Direct, CNKI, WANFANG, and VIP databases were searched for randomized controlled trials on the effects of MI combined NIBS in motor function recovery after stroke until February 2024. The outcomes of interest were associated with body functions or structure (impairment) and activity (functional). The primary outcome was assessed with the Fugl-Meyer assessment of the upper extremity (FMA-UE) for motor function of the upper limbs and the modified Barthel Index (MBI) for the ability to perform daily living activities. For secondary outcomes, functional activity level was measured using wolf motor function test (WMFT) and action research arm test (ARAT), and cortical excitability was assessed using cortical latency of motor evoked potential (MEP-CL) and central motor conduction time (CMCT). The methodological quality of the selected studies was evaluated using the evidence‑based Cochrane Collaboration’s tool. A meta-analysis was performed to calculate the mean differences (MD) or the standard mean differences (SMD) and 95% confidence intervals (CI) with random-effect models. Results A total of 14 articles, including 886 patients, were reviewed in the meta-analysis. In comparison with MI or NIBS alone, the combined therapy significantly improved the motor function of the upper limbs (MD = 5.43; 95% CI 4.34–6.53; P