Polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were prepared by emulsion polymerization and loaded with an enhanced green fluorescent protein plasmid (pEGFP) encoding human brain-derived neurotrophic factor (BDNF). This study investigated the potential effects of PBCA-pEGFP-BDNF NPs for the treatment of experimental cerebral hemorrhage mouse model animals.

Eight-week-old male mice (30 ± 5 g) were randomly divided into four groups (sham, intracerebral hemorrhage (ICH), ICH+PBCA NPs, and ICH+ PBCA-pEGFP-BDNF NPs; n = 14). An ICH model was constructed by right striatum injection of bacterial collagenase VII. Neurological function was evaluated by modified Garcia score after treatment of ICH mice with PBCA-pEGFP-BDNF NPs. The area of cerebral hematoma was measured and the water content of brain tissues was calculated by the wet/dry ratio method. Finally, immunofluorescence staining was used to detect neuron-specific nuclear protein (NeuN) positive cells around hematomas. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and western blot were used to detect inflammatory BDNF, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and either interleukin-1 beta (IL-1β) mRNA or protein levels.

Treatment with PBCA-pEGFP-BDNF NPs significantly improved neurological function and reduced acute brain edema and neuroinflammation in the mouse model of ICH. qPCR, ELISA, and western blot results showed that PBCA-pEGFP-BDNF NPs increased BDNF expression, inhibited NF-κB signaling pathway activity, and decreased the levels of inflammatory factors (IL-6, TNF-α, IL-1β) when compared with the recombinant plasmid pEGFP-BDNF.

PBCA-pEGFP-BDNF NPs improves neurological function in experimental ICH mice at least in part related to increased BDNF expression and decreased p65 NF-κB signaling axis activation, suggesting that PBCA NPs might be a suitable pEGFP-BDNF-carrying delivery system for ICH treatment.

Stroke survivors often experience varying levels of psychological stress, depression, and anxiety, which can exacerbate their physical impairments and adversely affect their recovery process. Virtual reality (VR) technology has been proven to be effective for patients with depression, garnering significant interest from researchers focused on stroke rehabilitation. However, the precise impact of VR on stroke-related psychology remains unclear. This meta-analysis aimed to appraise the effect of VR on depression, anxiety, and the abilities of daily living in stroke survivors.

The research involved a search of six electronic databases, including the Cochrane Library, Embase, Web of Science, PubMed, CINAHL, and PsycINFO, from the inception of the databases to June 2, 2024. Two investigators independently screened the databases based on the inclusion and exclusion criteria, extracted data from the included studies, and tested their methodological quality using Cochrane’s risk of bias tool. The intervention effect was estimated using Review Manager 5.4 to calculate the standard mean difference (SMD) and 95% confidence interval (CI).

This review identified 16 studies out of the 4439 records retrieved, consisting of a total of 756 stroke patients. Post-intervention analysis provided low certainty evidence that VR training reduced depression (SMD = –0.47; 95% CI: –0.88, –0.05, p = 0.03), but there was no significant effect on anxiety (SMD = –0.25; 95% CI: –0.53, 0.03, p = 0.08) and activities of daily living (SMD = 0.34; 95% CI: –0.05, 0.73, p = 0.09). Subgroup analysis indicated that participants under 60 years old who received VR intervention had a significant reduction in depression scores (SMD = –1.13; 95% CI: –1.89, –0.37, p = 0.004) compared with the control group. Those with moderate depression (SMD = –1.02; 95% CI = –1.96 to –0.07, p = 0.04) and intervention that lasted more than 6 weeks (SMD = –1.16; 95% CI: –1.87, –0.44, p = 0.002) also showed lower scores.

Due to heterogeneity concerns and the poor quality of included studies, our meta-analysis that provided evidence with very low certainty indicates that VR technology may be a beneficial approach for improving the psychological health issues faced by stroke survivors, helping to reduce their depression, but has no significant effect on reducing anxiety and improving their activities of daily life. However, additional comprehensive research is required to reinforce these conclusions. Specifically, future research needs to involve larger scale and more rigorous approaches, utilizing tailored VR interventions to further improve patient well-being.

CRD42024575981, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024575981.

Spatial working memory (SWM) deficit is a common problem in attention deficit disorder with hyperactivity (ADHD), often correlating with the severity of ADHD symptoms and academic difficulties. Although previous studies have broadly described abnormal brain structural changes in ADHD, the potential changes in brain morphology in children with ADHD with SWM dysfunction are still uncharacterized. This cross-sectional study was used to elucidate the brain morphological alterations associated with SWM performance in boys with ADHD.

Data for this investigation were retrieved from one public dataset. A cohort of 23 boys diagnosed with ADHD and an age-matched group of 23 healthy male controls were selected for the study. Participants were administered n-back SWM tasks, with task accuracy and response times recorded. Voxel-based morphometry (VBM) was used to quantify gray matter (GM) volume, thereby characterizing the brain morphological features in both the ADHD and healthy control groups. Linear or rank correlation analyses were conducted to examine the relationship between GM volume and SWM task performance.

VBM analysis revealed significantly lower GM volume in the right middle cingulate cortex (MCC), left precuneus, and right retrosubicular region among boys with ADHD. Moreover, a significant positive correlation was observed between the GM volume of the right MCC and the accuracy of the 2-back SWM task under conditions of small reward and immediate feedback.

The reduced GM volume in the right MCC, left precuneus, and right retrosubicular might have a potential impact on SWM performance in children with ADHD.

Neuropsychiatric disorders make up 14% of the global disease burden and are the leading cause of disability from noncommunicable diseases worldwide. The primary treatment for these disorders is drug therapy. Nonetheless, these therapies do not work completely for most patients, and even with attempts to create novel drugs, no medication has been confirmed as safe and effective for treating neuropsychiatric disorders. Recent studies have emphasized the role of gene therapy in neuropsychiatric disorders. Unc-51-like kinase (ULK) has connections to central nervous system functions and disorders, but the role of ULK4 is less well understood than other members of that family.

The PubMed database was searched for articles regarding ULK4 in neuropsychiatric disorders and neurodevelopment with no restriction on publication date.

ULK4 is believed to function as a pseudokinase, potentially acting as a scaffold to connect kinases or other enzymes with their substrates or to manage the subcellular location of interacting proteins in different biological processes, abnormal low expression of which may increase the risk of neuropsychiatric disorders.

This review updates the latest evidence on the roles of ULK4 in brain development and neuronal function, and highlights some controversies and uncertainties in the current research on ULK4. This review offers perspectives on the continuous development and design of drugs targeting ULK4, supporting possibilities for their future clinical application.

Functional mobility, which encompasses movements required for everyday activities, involves the ability to perform two tasks simultaneously, a concept known as dual-tasking (DT). The impact of interference between these tasks is observed by comparing the performance of a single task with that of the same task when associated with a second task, known as the dual-task effect (DTE). The decline in these functions due to aging and the associated increase in DTE might impair basic functions involving mobility, consequently increasing the risk of falls. Thus, this study aims to evaluate the DTE in functional mobility tasks across young, middle-aged, and older adults and to examine how different types of secondary tasks affect DT performance.

This laboratory-based cross-sectional observational study involved forty-four young adults (32.5 ± 6.9 years), thirty-five middle-aged adults (54.6 ± 6.3 years), and twenty-eight older adults (73.9 ± 7.0 years). DT conditions included performing three functional mobility tasks (the 3-meter Walking Test, Figure-8 Walk, and Four Square Step Test) alone and simultaneously with four different secondary tasks [Coin Transference (CTT), Stroop Color Word (SCWT), Digit Span (DST), and Semantic Verbal Fluency (SVFT) tasks]. The time taken to complete the mobility tasks was measured, while performance on secondary tasks was assessed based on the CTT rate, number of errors (SCWT and DST), and rate of recalled words (SVFT). The DTE was calculated, and patterns of dual-task cost were analyzed across all task conditions.

Decreases in functional mobility performance during dual-task performance were observed across all experimental groups. Older adults took longer to perform complex tasks involving turning and anterior/lateral/posterior displacements during dual-task conditions compared to young and middle-aged adults. The CTT and SCWT caused a high level of interference under dual-task conditions, while the SVFT and DST induced reduced impairments in functional mobility tasks. Most dual-task conditions led to “mutual interference”, where participants performed worse on both the primary and secondary tasks in the dual-task conditions.

All primary functional mobility tasks experienced interference under dual-task conditions. The relationship between dual motor and cognitive tasks may depend on the difficulty level presented to a given population. This study highlights the importance of understanding dual-task interference to develop targeted interventions for reducing fall risk, especially in older adults.

Peripheral immune cells participate in the pathogenesis and progression of central nervous system diseases including relapsing-remitting multiple sclerosis (RRMS), which is an immune-mediated demyelinating disorder. The association between IL-6 and RRMS pathogenesis is clear but there is some uncertainty about the role of IL-6 and IL-6 pathway components in blood and the molecular mechanisms through which T regulatorys (Tregs) contribute to MS pathogenesis. The purpose of this study was to identify markers of IL-6 pathways in serum and regulatory CD8⁺ and CD4⁺ T cells in the blood of RRMS patients and to analyze their associations with multiple sclerosis, with each other, and with age.

Peripheral blood was collected from female RRMS patients (16), and healthy controls (18) recruited between December, 2019 and July, 2022. The serum levels of IL-6, TGF-β1, IL-6Rα, IL-6/IL-6Rα complex, and soluble glycoprotein-130 (sgp-130) were measured by ELISA. Flow cytometry was used to quantify the surface expression of IL-6R (CD126), membrane glycoprotein 130 (gp130, CD130), and phospho-STAT3 (pSTAT3) and pSTAT5 in CD4⁺CD25⁺FoxP3⁺, CD8⁺CD25⁺FoxP3⁺, and CD8⁺CD122⁺ Tregs. Differences were compared using the Student’s t-test or Welch’s t-test. Pearson product-moment correlations were used to detect correlations. A p-value ≤ 0.05 was considered statistically significant.

The CD8⁺CD122⁺ Treg subset in RRMS patients exhibited an increased level of surface CD126 and CD130 associated with classical IL-6R signaling without STAT3 phosphorylation. For CD4⁺CD25⁺FoxP3⁺ and CD8⁺CD25⁺FoxP3⁺ Tregs, no changes in classical IL-6R surface markers were observed in RRMS, but there was an increased percentage of pSTAT3 in these cells. Age-related changes in pSTAT5 expression across Treg subsets in healthy controls were absent in RRMS patients.

Our findings underscore the complex interplay between IL-6 signaling and Tregs as well as age-related immune regulation. The observed alterations in the expression of receptors and in signaling activity may contribute to the dysregulation of CD8⁺CD122⁺ Treg function activated via the classic IL-6 pathway and suggests IL-6 trans-signaling in CD25-positive Tregs. RRMS may interfere with normal immune aging patterns, possibly by promoting a sustained inflammatory state that overrides the senescence of Tregs.

Preterm infants are commonly exposed to hyperoxia, which can induce hyperoxia-induced white matter injury (WMI), commonly resulting in cognitive deficits. Existing neonatal rat models of WMI show significant variability. Therefore, this study aimed to develop a reliable rat model of hyperoxia-induced WMI.

Two-day-old male newborn rats were randomly assigned to either the hyperoxia (HO) or the normoxia (NO) group. Mice in the HO group were exposed to a high-oxygen-inspired fraction (0.80) for either 24 h, 48 h, 5 d, 7 d, or 10 d, while the NO group was exposed to the standard oxygen-inspired fraction (0.21). Histological examination, immunofluorescence staining, western blot analysis, and transmission electron microscopy were performed to observe myelinogenesis. The Morris water maze test was used to assess cognitive function. The proliferation, migration, differentiation, and apoptosis of oligodendrocytes in the corpus callosum (CC) were evaluated using immunofluorescence. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were quantified to evaluate oxidative stress and inflammatory responses within the cerebral tissue.

Following hyperoxic exposure, demyelination and poor performance in the Morris water maze test were observed in the HO group, notably within the 5 d subgroup (p < 0.05). In addition, compared with the NO group, there were significant oligodendrocyte apoptosis, oxidative stress, and inflammatory responses in ROS, MDA, IL-1β, TNF-α, GFAP, and Iba-1 within the cerebral tissue of the HO group. The numbers of Ki67⁺/oligodendrocyte transcription factor 2 (Olig2)⁺ and Vimentin⁺/Olig2⁺ cells in the NO and HO groups were not significantly different (p > 0.05). Compared with the NO group, the average fluorescence intensity of Nerve-glia antigen 2 (NG2) and oligodendrocyte-specific marker 4 (O4) in the CC of the HO group increased, whereas the number of cyclic nucleotide phosphodiesterase (CC1) -positive cells significantly decreased (p < 0.05).

Hyperoxia causes WMI in neonatal rat brains. Exposure of neonatal rats to 80% oxygen for 5 d induces a reliable animal model of hyperoxia-induced WMI. Aberrant differentiation and apoptosis of oligodendrocytes might be the reason for hyperoxia-induced WMI.

Epilepsy is a neurological syndrome with a significant associated morbidity and mortality. An electroencephalogram (EEG) is an important tool to assist in the diagnosis of epilepsy. Sleep deprivation is a well-known risk factor for seizures and forms a basis for why sleep-deprived EEGs may assist in diagnosing epilepsy. There is mixed evidence regarding the utility of sleep deprivation in identifying signs of seizure activity, known as epileptiform activity. This study aimed to assess whether sleep-deprived EEGs increase the yield of epileptiform activity, compared with routine EEGs.

This was a retrospective observational study (January, 2018 to January, 2023) in patients of all ages who underwent routine and sleep-deprived EEGs at a major tertiary referral centre. Descriptive statistical analysis was undertaken in addition to the Fisher exact test and McNemar test to facilitate comparison of matched pairs.

There were 116 patients included in the study. The median age at time of first EEG was 32.5 years (interquartile range (IQR) 18–53). Fifty four percent of patients were male and 80% of patients were aged ≥18 years. The diagnostic yield of epileptiform activity was 21% when the results of both the routine and sleep-deprived EEG studies were included. There was no significant difference in the yield of epileptiform activity in routine versus sleep-deprived EEGs (12% versus 13% respectively, p = 1.0). Nine patients had epileptiform activity present on routine but not sleep-deprived EEG, and the reverse was true for 10 patients. There were several study limitations, including the varied time interval between EEG studies and limited referral documentation.

The study findings suggest that, in the correct clinical context, undertaking both a routine and sleep-deprived EEG, regardless of the order, may have benefit in identifying epileptiform activity. These findings also reinforce important data points that should be included with EEG referrals, to help optimise future research in this area.

Directing attention to relevant visual objects while ignoring distracting stimuli is crucial for effective perception and goal-directed behavior. Event-related potential (ERP) studies using the additional-singleton paradigm have provided valuable insights into how the human brain processes competing salient stimuli by monitoring N2pc and P_D, two event-related components thought to reflect target selection and distractor suppression, respectively. However, whether these components reflect the activity of a single or distinct neural mechanism remains controversial. Herein, we investigated the neural substrate of N2pc and P_D by manipulating the vertical elevation of target and distractor relative to the visual horizontal meridian using two variants of the additional-singleton paradigm.

In Experiment 1, participants searched for a shape singleton and identified the orientation of an embedded tilted bar while ignoring a color singleton. In Experiment 2, the tilted bars were removed and participants performed a shape search while ignoring a color singleton. Electroencephalogram (EEG) recordings at posterior sites (PO7/8) measured N2pc and P_D components. Reaction times and ERP amplitudes were analyzed across conditions.

The results of both Experiments 1 and 2 showed that N2pc and P_D responded in opposite ways to the manipulation of vertical elevation. N2pc was robust for targets in the lower visual hemifield and reversed in polarity (i.e., post-N2pc positivity ) for targets in the upper visual hemifield. Conversely, P_D was more pronounced for distractors in the upper visual hemifield and nil for those in the lower visual hemifield. Critically, vertical elevation did not influence psychophysical estimates of search efficiency in either experiment, suggesting that the relationship between these components and their functional significance is less straightforward than previously thought.

These results provide empirical support for the idea that N2pc and P_D are influenced by the retinotopic organization of the visual cortex in a manner consistent with the neural and functional dissociation of target selection and distractor suppression in visual search.

Executive function (EF) impairment is a recognized common cognitive deficit in early-onset Parkinson’s disease (EOPD), profoundly impacting patient autonomy and quality of life. While EF-related cognitive decline has been extensively studied in late-onset Parkinson’s disease (LOPD), research on EOPD remains limited. Addressing this gap, this study uniquely employed functional near-infrared spectroscopy (fNIRS), a technique well-adapted for assessing patients with motor challenges, to explore EF-related neural mechanisms in EOPD patients with mild cognitive impairment.

This study included 30 patients with PD, classified into distinct cognitive profiles based on comprehensive assessments of their cognitive function. To assess functional changes in the prefrontal cortex (PFC) we administered a verbal fluency test to evaluate EF during task performance. In the resting state, we recorded neural activity and analyzed the amplitude of low-frequency fluctuations (ALFF) to assess spontaneous brain activity.

During executive tasks, patients with EF-dominant impairment (EOPD-EL) showed increased activation in the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC), indicating disrupted balance between the executive and default mode networks. Resting-state analysis revealed reduced spontaneous activity in the ventrolateral prefrontal cortex (VLPFC), suggesting impaired regulatory efficiency in these regions. These findings support the dual syndrome hypothesis in EOPD, with EF dysfunction as a primary deficit that may lead to secondary cognitive challenges.

This study underscores the central role of PFC dysfunction in EOPD-related EF impairment, identifying abnormalities in the DLPFC, mPFC, and VLPFC as key contributors to cognitive decline. These results lay the groundwork for early detection of EF deficits and inform targeted interventions to mitigate cognitive decline in EOPD.

Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in spinal cord injury (SCI) and its relationship with autophagy, which is essential for cellular homeostasis, warrant further investigation.

We established a mouse model of SCI using complete spinal transection. The neuroprotective effects of LTG were assessed using immunostaining and functional assessments, including Basso Mouse Scale (BMS) scores, lesion site area, and synapse survival. Western blot analyses were also performed to further examine the underlying cellular and molecular mechanisms of autophagy.

LTG treatment promoted the post-traumatic survival of spinal neurons, improved BMS scores, reduced lesion site area, and enhanced synapse survival in a mouse model of SCI. Furthermore, LTG attenuated apoptosis following SCI by activating autophagy during the secondary injury phase. These findings indicate that LTG-enhanced autophagosome formation and autolysosome degradation play a key role in reducing neuronal loss after SCI.

LTG appears to attenuate post-traumatic spinal neural injury by enhancing autophagy flux.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare disease with a high disability rate, characterized by acute-to-subacute psychiatric and/or neurological symptoms. Continuous intrathecal antibody synthesis does not correlate with the active phase of encephalitis and antibody titers do not directly reflect the severity of the condition. Currently, there is a lack of biomarkers for disease monitoring. This study focuses on finding novel peripheral blood biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis.

Peripheral blood samples were collected from patients with anti-NMDAR encephalitis, including those with acute-phase (autoimmune encephalitis (AE)-a group) and stable-phase (AE-s group) autoimmune encephalitis. Healthy individuals were included as controls (HC group). We isolated exosomal microRNAs (miRNAs) from the samples and screened differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using quantitative real-time qPCR (RT-qPCR). Furthermore, we conducted a correlation analysis between the expression levels of the screened miRNAs and clinical severity. Finally, we performed functional pathway analysis to explore the underlying mechanisms in anti-NMDAR encephalitis.

We found that exosomal miR-432-5p, miR-4433b-5p, and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at various phases of the disease. The expression of miR-432-5p and miR-4433b-5p were negatively correlated with clinical severity. We further identified that key pathways including rhythmic processes and glutamatergic signaling play significant roles in the pathogenesis of anti-NMDAR encephalitis.

Our research indicated that exosomal miR-432-5p, miR-4433b-5p, and miR-599 were correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. Moreover, the key functional pathways predicted by these miRNAs may play crucial roles in disease progression.