Beam Walking Research Articles

6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1β (IL-1β), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.

C-phycocyanin shows neuroprotective effect against rotenone-induced Parkinson’s disease in mice

Objective: To investigate the neuroprotective effect of C-phycocyanin in a mouse model of rotenone-induced Parkinson’s disease. Methods: C-phycocyanin (50 mg/kg, i.p., daily) was administered to rotenone (30 mg/kg, p.o., daily) treated mice for 28 days. Behavioral studies (Y-maze, rotarod, round beam walk, and wire-hang tests) were carried out to assess neurobehavioral deficits. Glutathione and malondialdehyde were determined in both serum and striatal tissue. Molecular proteins (AKT, AMPK, NF-κB, BDNF, and alpha-synuclein) in the striatum were estimated using ELISA. Histopathological analyses (hematoxylin and eosin stainning as well as Nissl staining) were carried out to assess structural abnormalities in the striatum. Results: C-phycocyanin significantly increased BDNF levels and decreased alpha-synuclein levels. It also slightly upregulated AMPK and AKT levels without significant difference compared with the rotenone group. Additionally, rotenone-induced elevated oxidative stress and structural abnormalities in the striatum were markedly mitigated by C-phycocyanin. Conclusions: C-phycocyanin might have potential neuroprotective effects against Parkinson’s disease. Further studies are warranted to verify its efficacy and to understand the molecular mechanisms behind the neuroprotective effects of C-phycocyanin in Parkinson’s disease.

Bradykinin 2 Receptors Mediate Long-Term Neurocognitive Deficits After Experimental Traumatic Brain Injury.

The kallikrein-kinin system is one of the first inflammatory pathways to be activated following traumatic brain injury (TBI) and has been shown to exacerbate brain edema formation in the acute phase through activation of bradykinin 2 receptors (B2R). However, the influence of B2R on chronic post-traumatic damage and outcome is unclear. In the current study, we assessed long-term effects of B2R-knockout (KO) after experimental TBI. B2R KO mice (heterozygous, homozygous) and wild-type (WT) littermates (n = 10/group) were subjected to controlled cortical impact (CCI) TBI. Lesion size was evaluated by magnetic resonance imaging up to 90 days after CCI. Motor and memory function were regularly assessed by Neurological Severity Score, Beam Walk, and Barnes maze test. Ninety days after TBI, brains were harvested for immunohistochemical analysis. There was no difference in cortical lesion size between B2R-deficient and WT animals 3 months after injury; however, hippocampal damage was reduced in B2R KO mice (p = 0.03). Protection of hippocampal tissue was accompanied by a significant improvement of learning and memory function 3 months after TBI (p = 0.02 WT vs. KO), whereas motor function was not influenced. Scar formation and astrogliosis were unaffected, but B2R deficiency led to a gene-dose-dependent attenuation of microglial activation and a reduction of CD45+ cells 3 months after TBI in cortex (p = 0.0003) and hippocampus (p < 0.0001). These results suggest that chronic hippocampal neurodegeneration and subsequent cognitive impairment are mediated by prolonged neuroinflammation and B2R. Inhibition of B2R may therefore represent a novel strategy to reduce long-term neurocognitive deficits after TBI.

Reduced inhibitory synaptic transmission onto striatopallidal neurons may underlie aging-related motor skill deficits

Human beings are living longer than ever before and aging is accompanied by an increased incidence of motor deficits, including those associated with the neurodegenerative conditions, Parkinson's disease (PD) and Huntington's disease (HD). However, the biological correlates underlying this epidemiological finding, especially the functional basis at the synapse level, have been elusive. This study reveals that motor skill performance examined via rotarod, beam walking and pole tests is impaired in aged mice. This study, via electrophysiology recordings, further identifies an aging-related reduction in the efficacy of inhibitory synaptic transmission onto dorsolateral striatum (DLS) indirect-pathway medium spiny neurons (iMSNs), i.e., a disinhibition effect on DLS iMSNs. In addition, pharmacologically enhancing the activity of DLS iMSNs by infusing an adenosine A2A receptor (A2AR) agonist, which presumably mimics the disinhibition effect, impairs motor skill performance in young mice, simulating the behavior in aged naïve mice. Conversely, pharmacologically suppressing the activity of DLS iMSNs by infusing an A2AR antagonist, in order to offset the disinhibition effect, restores motor skill performance in aged mice, mimicking the behavior in young naïve mice. In conclusion, this study identifies a functional inhibitory synaptic plasticity in DLS iMSNs that likely contributes to the aging-related motor skill deficits, which would potentially serve as a striatal synaptic basis underlying age being a prominent risk factor for neurodegenerative motor deficits.

Analysisof Beam Walk in Inter-Satellite Laser Link: Implications for Differential Wavefront Sensing in Gravitational Wave Detection

Achieving space-based gravitational wave detection requires the establishment of an interferometer constellation. It is necessary to establish and maintain stable laser interferometric links using the differential wavefront sensing (DWS) technnique. When the distant measurement beam experiences pointing jitter, it causes beam walk on the surface of the local detector. The reduced overlap between the local reference spot and the distant spot increases the nonlinear errors in the DWS technique, which need to be suppressed. Numerical analysis was conducted on the spatial beam interference signals of the DWS technique when the distant measurement beam experienced pointing jitter. An experimental measurement system was designed, and the beam walk was suppressed using a conjugate imaging system. The results show that within a range of 300 μrad, the optical path with the imaging system can reduce measurement errors by at least 83%. This way also helps to reduce pointing jitter noise in inter-satellite links, thereby improving laser pointing control accuracy.This method would provide a valuable reference for future DWS measurement systems.

Intermittent fasting induced cerebral ischemic tolerance altered gut microbiome and increased levels of short-chain fatty acids to a beneficial phenotype

Preconditioning-induced cerebral ischemic tolerance is known to be a beneficial adaptation to protect the brain in an unavoidable event of stroke. We currently demonstrate that a short bout (6 weeks) of intermittent fasting (IF; 15 h fast/day) induces similar ischemic tolerance to that of a longer bout (12 weeks) in adult C57BL/6 male mice subjected to transient middle cerebral artery occlusion (MCAO). In addition, the 6 weeks IF regimen induced ischemic tolerance irrespective of age (3 months or 24 months) and sex. Mice subjected to transient MCAO following IF showed improved motor function recovery (rotarod and beam walk tests) between days 1 and 14 of reperfusion and smaller infarcts (T2-MRI) on day 1 of reperfusion compared with age/sex matched ad libitum (AL) controls. Diet influences the gut microbiome composition and stroke is known to promote gut bacterial dysbiosis. We presently show that IF promotes a beneficial phenotype of gut microbiome following transient MCAO compared with AL cohort. Furthermore, post-stroke levels of short-chain fatty acids (SCFAs), which are known to be neuroprotective, are higher in the fecal samples of the IF cohort compared with the AL cohort. Thus, our studies indicate the efficacy of IF in protecting the brain after stroke, irrespective of age and sex, probably by altering gut microbiome and SCFA production.

Neuroprotective effect of marrubiin against MPTP-induced experimental Parkinson’s disease in male wistar rats

In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson’s disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1β, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (p < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (p < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (p < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1β, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin’s neuroprotective ability have to be studied in detail.

Effects of the Pharmabiotic U-21 under Conditions of a Combined Neuroinflammatory Model of Parkinson's Disease in Rats.

Data on the participation of microbiota in the development of Parkinson's disease allow us to discuss the ability of bacterial preparations to influence the processes leading to neurodegeneration. We studied the effect of oral administration of Limosilactobacillus fermentum U-21 lyophilisate on a model of Parkinson's disease in rats induced by combined intranigral injection of LPS and systemic administration of paraquat. The toxins significantly increased the number of missteps in the "narrowing beam walking" test, but a tendency to a decrease in this parameter was shown after treatment with U-21. It should be noted that U-21 did not reduce the neuronal death in the substantia nigra, but mitigated the inflammatory glial response, decreased the accumulation of phosphorylated α-synuclein and complement protein C3. Our study demonstrated the efficiency of the combined model of parkinsonism and reduction of proinflammatory changes under the influence of pharmabiotic without changes in the nigral neuronal death and motor deficits.

Effect of low versus high balance training complexity on balance performance in male adolescents

ObjectiveThe current study aimed to determine the effects of low (i.e., balance task only) versus high (i.e., balance task combined with an additional motor task like dribbling a basketball) balance training complexity (6 weeks of training consisting of 2 × 30 min balance exercises per week) on measures of static and dynamic balance in 44 healthy male adolescents (mean age: 13.3 ± 1.6 years).ResultsIrrespective of balance training complexity, significant medium- to large-sized pretest to posttest improvements were detected for static (i.e., One-Legged Stance test, stance time [s], 0.001 < p ≤ 0.008) and dynamic (i.e., 3-m Beam Walking Backward test, steps [n], 0.001 < p ≤ 0.002; Y-Balance-Test-Lower-Quarter, reach distance [cm], 0.001 < p ≤ 0.003) balance performance. Further, in all but one comparison (i.e., stance time with eyes opened on foam ground) no group × test interactions were found. These results imply that balance training is effective to improve static and dynamic measures of balance in healthy male adolescents, but the effectiveness seems unaffected by the applied level of balance training complexity.

In Vivo Study of Moringa oleifera Seed Extracts as Potential Sources of Neuroprotection against Rotenone-Induced Neurotoxicity.

Parkinson's disease (PD) is a leading neurodegenerative disorder affecting 1-3 percent of the elderly population. Oxidative stress is the primary factor for the neurodegeneration of Substantia Nigra (SN). The current study aims to assess the seed extracts of Moringa oleifera (MO) on rotenone-mediated motor function impairments in a PD mouse model. For this purpose, two different seed extracts of MO were prepared, including aqueous MO (AqMO) and ethanolic MO (EthMO). Male Swiss albino mice were grouped into five groups. Mice received 2.5 mg/kg rotenone for 21 consecutive days, and control mice received the vehicle. Extract-treated mice received 200 mg/kg AqMO and EthMO separately, orally and daily for 28 days. Sinemet-treated mice received 20 mg/kg, oral dose, as a positive group. The motor function performance was evaluated using standard neurobehavioral tests. The antioxidant potentials of MO seed extracts were estimated by lipid peroxidation (LPO), reduced glutathione (GSH), glutathione-s-transferase (GST) and catalase (CAT) activities in mice brain homogenates. The PD mice brain SN sections were investigated for neurodegeneration. MO seed extract-treated mice showed a significant reduction in motor dysfunction compared to rotenone-treated mice as assessed through the open field, beam walk, pole climb-down, tail suspension, stride length and stepping tests. Increased antioxidant capacities of the PD mice brains of MO extract-administered groups were observed compared to the control. A histological study showed reduced signs of neurodegeneration, vacuolation around multipolar cells and cytoplasmic shrinkage in MO extract-treated mice SN brain sections. Collectively, MO seed extracts protected the animals from locomotor deficits induced by rotenone, possibly through antioxidant means, and seem to have potential applications in neurodegenerative diseases.

Walking on a Balance Beam as a New Measure of Dynamic Balance to Predict Falls in Older Adults and Patients with Neurological Conditions.

Beam walking is a new test to estimate dynamic balance. We characterized dynamic balance measured by the distance walked on beams of different widths in five age groups of healthy adults (20, 30, 40, 50, 60years) and individuals with neurological conditions (i.e., Parkinson, multiple sclerosis, stroke, age: 66.9years) and determined if beam walking distance predicted prospective falls over 12months. Individuals with (n = 97) and without neurological conditions (n = 99, healthy adults, age 20-60) participated in this prospective longitudinal study. Falls analyses over 12months were conducted. The summed distance walked under single (walking only) and dual-task conditions (walking and serial subtraction by 7 between 300 to 900) on three beams (4, 8, and 12-cm wide) was used in the analyses. Additional functional tests comprised grip strength and the Short Physical Performance Battery. Beam walking distance was unaffected on the 12-cm-wide beam in the healthy adult groups. The distance walked on the 8-cm-wide beam decreased by 0.34m in the 20-year-old group. This reduction was ~ 3 × greater, 1.1m, in the 60-year-old group. In patients, beam walking distances decreased sharply by 0.8m on the 8 versus 12cm beam and by additional 1.6m on the 4 versus 8cm beam. Beam walking distance under single and dual-task conditions was linearly but weakly associated with age (R2 = 0.21 for single task, R2 = 0.27 for dual-task). Age, disease, and beam width affected distance walked on the beam. Beam walking distance predicted future falls in the combined population of healthy adults and patients with neurological conditions. Based on receiver operating characteristic curve analyses using data from the entire study population, walking ~ 8.0 of the 12m maximum on low-lying beams predicted future fallers with reasonable accuracy. Balance beam walking is a new but worthwhile measure of dynamic balance to predict falls in the combined population of healthy adults and patients with neurological conditions. Future studies are needed to evaluate the predictive capability of beam walking separately in more homogenous populations. Clinical Trial Registration Number NCT03532984.

Corticomuscular and intermuscular coherence as a function of age and walking balance difficulty

We determined beta-band intermuscular (IMC) and corticomuscular coherence (CMC) as a function of age and walking balance difficulty. Younger (n=14, 23y) and older individuals (n=19, 71y) walked 13 m overground, on a 6-cm-wide ribbon overground, and on a 6-cm-wide (5-cm-high) beam. Walking distance as a proxy for walking balance and speed were computed. CMC was estimated between electroencephalographic signal at Cz electrode and surface electromyographic signals of seven leg muscles, while IMC was calculated in four pairs of leg muscles, during stance and swing gait phases. With increasing difficulty, walking balance decreased in old individuals and speed decreased gradually independent of age. Beam walking increased IMC, while age increased IMC in proximal muscle pairs, and decreased IMC in distal muscle pairs. Age and difficulty increased CMC independent of gait phases. Concluding, CMC and IMC increased with walking balance difficulty and age, except for distal muscle pairs, which had lower IMC with age. These findings suggest an age-related increase in corticospinal involvement in the neural control of walking balance. Data AvailabilityThe datasets used in this study are available from the corresponding author upon reasonable request.

The Effects of Mkpuru Mmiri Consumption on Cognitive Performance and Brain Histology in an Animal Study

Mkpuru mmiri, popularly known as ice or methamphetamine (METH) is one of the illegal substances that young people in Nigeria abuse most frequently. The purpose of the study is to determine how methamphetamine affects the cognitive-motor behavior of Wistar rats. In the study, twenty-five Wistar rats weighing between 117 and 138 grams were split into five groups: group A had only rat feed and water, group B - D received doses of METH ranging from 5 mg/kg to 20 mg/kg, and group E received a dose of 5 mg/kg of diazepam. Neurobehavioral tools such as the navigator maze test, elevated plus maze and beam walk were used to assess the rats’ memory, anxiety-related behavior, balance, motor coordination, and working memory respectively. Two weeks after the injection, samples were taken and examined for oxidative stress markers (Malondialdehyde - MDA) and tissue antioxidant indicators (Superoxide dismutase - SOD, Glutathione - GSH, and Total Antioxidant Capacity - TAC). The data were analyzed using SPSS and post hoc LSD and the significance level was established at p&lt;0.05. The results showed that the test groups' body weight was significantly lower than the control groups' (p&lt;0.05). The test groups' relative brain weights increased significantly (p&lt;0.05) when compared to the control group. The data also showed a significantly (p&lt;0.05), level of antioxidant enzymes (SOD, GSH, and TAC levels) and a significantly (p&lt;0.05) greater level of MDA when compared to the control group. When comparing the test groups' cognitive abilities to the controls, the experimental rats' cognitive powers significantly declined. The study's conclusion demonstrated that chronic consumption of methamphetamine may deteriorate cognitive function.

Cannabis sativa Boosts Brain Functions and Ameliorate Anxiety, when used Sensibly and not Abusively

Cannabis sativa is an illegal substance with documented analgesic, antipyretic, anti-inflammatory, and anti-diarrheal properties. Numerous other cannabinoids found in cannabis have an impact on brain activity. So, the purpose of this study was to examine how cannabis sativa extract affected the cognito-motor activity in rats. Twenty-four (24) Wistar rats weighing between 80.53 and 100.49g were randomly divided into four groups (A, B, C, and D) of six animals each after a 14-day acclimatization period to laboratory conditions. Only food and water were provided to Group A. Groups B and C received an oral ethanolic extract of Cannabis sativa at doses of 400 mg/kg and 800 mg/kg, respectively. Group D received an intraperitoneal dose of diazepam at a rate of 50 mg/kg. To ascertain the impact of the cannabis sativa extract on the neuro behavior of the rats, each animal in the four groups is subjected to an experimental test following each administration of the extract (the Barnes maze test, the beam walk test, and the inverted screen tests). The rats in groups B and C that received cannabis sativa extract showed a notable improvement in learning and memory, and the majority of the rats in group C who received cannabis sativa extract walked upright without stumbling. Group A, the control group, exhibited indicators of anxiety and panic but no discernible change in learning or memory. Due to muscle weakness, members of group D (standard drug group) were essentially inactive throughout the experiment, staggering and falling. It can be concluded that cannabis sativa's ethanolic leaf extract is not harmful, boosts brain functions, and promotes learning and memory when used sensibly and not abusively. Thus, it can be inferred that the plant may help with the treatment of several mental health conditions, such as anxiety.

Implication of Some Energy Drink Mixture with Flunitrazepam on Endurance Pattern and Cognitive/Motor Functions in Wistar Rats

This study was conducted to investigate the effects of some energy drinks mixture with Flunitrazepam on endurance pattern and cognitomotor activities in male Wistar rats. 45 Wistar rats were divided into 8 groups. Group 1 received distilled water; Group 2 received energy drink (A) (3.75 mg/kg). Group 3 energy drink (A) (7.5 mg/kg) Group 4 received energy drink (B) (3.75 mg/kg). Group 5 energy drink (B) (7.5 mg/kg) Group 6 received flunitrazepam (0.03 ml/kg), Group 7 received 3.75 ml/kg of energy drink (A) and 0.03 ml/kg of flunitrazepam, and Group 8 received 3.75 ml/kg of energy drink (B) and 0.03 ml/kg of flunitrazepam. Administration of the mixture lasted for 28 days while endurance test/Cognitive and motor functions test were conducted weekly using Handgrip test, beam walk test and navigational maze test. The result reveals significant improvement in endurance pattern and cognitomotor functions in groups administered with energy drinks alone at week one, however the mixture of energy drink with various doses of Flunitrazepam showed significant impairment in both endurance pattern, and cognitomotor activities. It was therefore concluded that while the combination of energy drinks and flunitrazepam may offer short-term benefits in terms of endurance, and alertness, there is a dose and time dependent significant decline in cognitive and motor functions functions in wistar rats. The findings suggest significant variations in endurance and cognitive-motor performance across different groups, highlighting the complex interactions between stimulant and sedative substances and their implications for health and behavior.

Neuroprotective potential of Mentha piperita extract prevents motor dysfunctions in mouse model of Parkinson's disease through anti-oxidant capacities.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Neurodegeneration of the substantia nigra (SN) and diminished release of dopamine are prominent causes of this progressive disease. The current study aims to evaluate the protective potential of ethanolic extract of Mentha piperita (EthMP) against rotenone-mediated PD features, dopaminergic neuronal degeneration, oxidative stress and neuronal survival in a mouse model. Swiss albino male mice were assigned to five groups: control (2.5% DMSO vehicle), PD (rotenone 2.5 mg/kg), EthMP and rotenone (200mg/kg and 2.5mg/kg, respectively), EthMP (200 mg/kg), and Sinemet, reference treatment containing levodopa and carbidopa (20 mg/kg and rotenone 2.5mg/kg). Behavioral tests for motor functional deficit analysis were performed. Anti-oxidant capacity was estimated using standard antioxidant markers. Histopathology of the mid-brain for neurodegeneration estimation was performed. HPLC based dopamine level analysis and modulation of gene expression using quantitative real-time polymerase chain reaction was performed for the selected genes. EthMP administration significantly prevented the rotenone-mediated motor dysfunctions compared to PD group as assessed through open field, beam walk, pole climb down, stepping, tail suspension, and stride length tests. EthMP administration modulated the lipid peroxidation (LPO), reduced glutathione (GSH), and superoxide dismutase (SOD) levels, as well as glutathione-s-transferase (GST) and catalase (CAT) activities in mouse brain. EthMP extract prevented neurodegeneration in the SN of mice and partially maintained dopamine levels. The expression of genes related to dopamine, anti-oxidant potential and synapses were modulated in M. piperita (MP) extract treated mice brains. Current data suggest therapeutic capacities of MP extract and neuroprotective capacities, possibly through antioxidant capacities. Therefore, it may have potential clinical applications for PD management.

The Cerebral Protective Effect of Novel Erinacines from Hericium erinaceus Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways.

Hericium erinaceus, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of H. erinaceus mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing H. erinaceus mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of H. erinaceus mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with H. erinaceus mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of H. erinaceus mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.

Time-course of balance training-related changes on static and dynamic balance performance in healthy children

ObjectiveIn healthy children, there is evidence of improvements in static and dynamic balance performance following balance training. However, the time-course of balance training-related changes is unknown. Thus, we determined the effects of balance training after one, three, and six weeks of exercise on measures of static and dynamic balance in healthy children (N = 44, 20 females, mean age: 9.6 ± 0.5 years, age range: 9–11 years).ResultsParticipants in the intervention group (2 × 25 min balance exercises per week) compared to those in the control group (2 × 25 min track and field exercises and soccer practice per week) significantly improved their static (i.e., by measuring stance time in the One-Legged Stance test) and dynamic (i.e., by counting step number in the 3-m Beam Walking Backward test) balance performance. Late effects (after 6 weeks) occurred most frequently followed by mid-term effects (after 3 weeks) and then early effects (after 1 week). These findings imply that balance training is effective to improve static and dynamic measures of balance in healthy children, whereby the effectiveness increases with increasing training period.Trial registrationCurrent Controlled Trials ISRCTN16518737 (retrospectively registered at 24th August, 2023).

Dihydroergotamine protects against ischemic stroke by modulating microglial/macrophage polarization and inhibiting inflammation in mice

ABSTRACT Objectives The search for drugs that can protect the brain tissue and reduce nerve damage in acute ischemic stroke has emerged as a research hotspot. We investigated the potential protective effects and mechanisms of action of dihydroergotamine against ischemic stroke. Methods C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO), and dihydroergotamine at a dose of 10 mg/kg/day was intraperitoneally injected for 14 days. Adhesive removal and beam walking tests were conducted 1, 3, 5, 7, 10, and 14 days after MCAO surgery. Thereafter, the mechanism by which dihydroergotamine regulates microglia/macrophage polarization and inflammation and imparts ischemic stroke protection was studied using enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting. Results From the perspective of a drug repurposing strategy, dihydroergotamine was found to inhibit oxygen-glucose deprivation damage to neurons, significantly improve cell survival rate, and likely exert a protective effect on ischemic brain injury. Dihydroergotamine significantly improved neural function scores and survival rates and reduced brain injury severity in mice. Furthermore, dihydroergotamine manifests its protective effect on ischemic brain injury by reducing the expression of TNF-α and IL-1β in mouse ischemic brain tissue, inhibiting the polarization of microglia/macrophage toward the M1 phenotype and promoting polarization toward the M2 phenotype. Conclusion This study is the first to demonstrate the protective effect of dihydroergotamine, a first-line treatment for migraine, against ischemic nerve injury in vitro and in vivo.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.