Damage To Cortex Research Articles

Sulfasalazine improves neuronal function in mice with ischemic stroke by inhibiting the STING/NF-κB pathway.

Inflammation plays an essential role in the pathological processes of ischemic stroke (IS). Sulfasalazine is used in clinical practice for the treatment of inflammatory diseases. This study investigated the effects of sulfasalazine in mice with IS and its underlying mechanisms. We employed an in vivo mice model of middle cerebral artery occlusion (MCAO)/reperfusion, investigating the impact of sulfasalazine on MCAO mice using tetrazolium chloride (TTC) staining, behavioral experiments, and pathological staining. Utilizing of network pharmacology methodologies, we speculated that the protective effect of sulfasalazine against IS may be related to inflammation. The effects of sulfasalazine on inflammation and polarization in oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced BV2 cells were examined through immunofluorescence and PCR techniques. Additionally, the influence of sulfasalazine on the STING/NF-κB pathway was assessed using Western blot and immunofluorescence techniques. Sulfasalazine significantly reduced the infarct area in MCAO mice, restored cerebral blood flow, and improved motor function in the MCAO mice. Pathological staining results indicated that sulfasalazine can mitigate neuronal damage in the cerebral cortex of MCAO mice. Immunofluorescence and PCR testing showed that sulfasalazine promotes M1 to M2 polarization, and reduces inflammation in OGD/R-induced BV2 cells. Furthermore, the Western blot and immunofluorescence results both confirmed that sulfasalazine can inhibit the activation of the STING/NF-κB pathway. This study elucidated the potential therapeutic role of sulfasalazine in IS through its anti-inflammatory effects and modulation of STING/NF-κB pathway, offering novel insights into treatment strategies for IS.

Relationship Between Cognitive Estimation, Executive Functions, and Theory of Mind in Patients With Prefrontal Cortex Damage.

Conflicting evidence has arisen from the few studies that have examined the role of the prefrontal cortex and executive control functions in theory of mind (ToM). Moreover, the involvement of other cognitive domains in the ability to infer mental states is still under debate. This study aims to examine, in addition to the potential contribution of executive functions, the role of cognitive estimation in ToM abilities, given that cognitive estimation processes are strongly associated with some aspects of executive control functions. The cognitive estimation task, along with a set of neuropsychological tasks assessing executive functions, was administered to 30 patients with prefrontal cortex damage and 30 control subjects matched by gender, age, and education level. Patients with prefrontal cortex damage were impaired in all measures of executive functions, cognitive estimation, and theory of mind compared with control subjects. Regression analysis showed a significant interaction between executive measures and cognitive estimation in predicting ToM performance for patients with prefrontal cortex damage. Additionally, voxel-based lesion analysis identified a partially common bilaterally distributed prefrontal network involved in all three domains, centered within the ventral and dorsomedial areas with extension to the dorsolateral prefrontal cortex. Our findings highlight that, apart from executive functions, cognitive estimation plays a crucial role in the ability to interpret others' cognitive and emotional states in both patients with prefrontal cortex damage and control subjects.

Gallic acid attenuates lipopolysaccharide - induced memory deficits, neurochemical changes, and peripheral alterations in purinergic signaling.

Neuroinflammation is associated with many neurological disorders. Gallic acid (GA) has attracted significant attention due to its biological properties, such as neuroprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the effects of GA in memory, TNF-α levels, oxidative stress, and activities of acetylcholinesterase (AChE), Na+, K+-ATPase and Ca2+-ATPase in the brain of mice exposed to lipopolysaccharide (LPS). Additionally, we evaluated alterations in adenine nucleotides and nucleosides in the serum. Male mice were orally pretreated with vehicle or GA (50 or 100mg/kg) for 14 days. Between days 8 and 14, the animals also received LPS injection (250µg/kg) or saline. At the end of the experimental protocol, the animals were submitted to object recognition test, euthanized and cerebral cortex, hippocampus, striatum and blood were collected. LPS induced memory deficits, which were prevented by GA treatment. GA protected against LPS-induced oxidative damage in the cerebral cortex, hippocampus and striatum by reducing reactive oxygen species and nitrite levels, while increasing total thiol content and activities of antioxidant enzymes. GA also prevented LPS-induced alterations in AChE, Na+, K+-ATPase, and Ca2+-ATPase activities in brain structures. LPS elevated TNF-α levels in the hippocampus and cerebral cortex, which were attenuated by GA treatment. Furthermore, LPS caused a reduction in ADP and AMP hydrolysis and an increase in adenosine deamination in the serum, which were also prevented by GA. The effects of GA against neuroinflammation may be attributed to its potent antioxidant and anti-inflammatory properties, which modulate various pathways, including those involved in memory mechanisms.

Application of TCM network pharmacology and experimental verification to explore the mechanism of kaempferol against epilepsy

BackgroundKaempferol (KF), the main active ingredient in identifying the authenticity of safflower, has a variety of pharmacological activities and neuroprotective effects. However, the mechanism of KF in the treatment of epilepsy remains unclear. This study aimed to investigate the protective effects of KF on epilepsy and its related mechanisms. MethodsNetwork pharmacology was used to explore the targets and mechanisms of safflower antiepileptic action. The protective effect of KF on epilepsy was assessed in the behavior and tissues of epileptic mice. Additionally, the impact of KF on the excitability and calcium transients of rat cortical neurons and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor (AMPAR) were investigated using patch clamp and calcium imaging techniques. ResultsNetwork pharmacology indicated safflower could be involved in calcium signaling pathways and calcium channel inhibitor activity. Experimental validation demonstrated that KF delayed seizure onset and mitigated neuronal damage in the prefrontal cortex of mice. It also reduced neuronal excitability, as indicated by action potential parameters, and suppressed Glutamate (Glu)-induced calcium transients. In tsA201 cells, KF inhibited AMPAR-mediated currents, suggesting a role in regulating [Ca2+]i homeostasis. ConclusionThese results indicate that KF's anticonvulsant properties may arise from its neuroprotection against cell injury, edema, and necrosis, its reduction of neuronal hyperexcitability, and its prevention of calcium-induced cytotoxicity, potentially involving AMPAR modulation. This study positions KF as a promising candidate for epilepsy therapy, offering a scientific foundation for its clinical investigation.

Optimal angles for independent femoral tunnel drillings to prevent damage to anatomic structures in single-bundle anterior cruciate ligament reconstruction

PurposeTo determine the optimal angles for independent femoral tunnel drillings in single-bundle anterior cruciate ligament reconstruction (ACLR) in different races and genders with the aim of preventing damage to lateral femoral anatomic structures (LFAS), posterior cortex and medial femoral condyle.MethodsThis study included 180 volunteers, including 90 Caucasian and 90 matched Chinese. Magnetic resonance imaging (MRI) was used to scan the knees to create three-dimensional bone models, the ACL femoral footprint centre and the LFAS. In each femur model, femoral tunnels were established using a set of 16 distinct angular combinations: 15°, 30°, 45°, and 60° in the axial plane, as well as 15°, 30°, 45°, and 60° in the coronal plane. The minimum distance from the tunnel exit to the LFAS was evaluated, and the tunnel length, posterior cortex damage and medial femoral condyle injury were assessed.ResultsAmong the 180 patients with simulated ACL femoral tunnels, there was damage to the anatomical structure in parts of the model. According to the Cochran Q test results (P < 0.001), the percentage of safe tunnels varied significantly among the 16 different drilling angle combinations. The overall occurrence of the tunnel exit causing injury to LFAS were 8.3% and 8.1% in Chinese and Caucasian groups (P = 0.786). The means for tunnel length in Caucasians was 40.1 ± 7.9 mm, respectively; for Chinese, the results was 38.8 ± 6.6 mm (P < 0.001). Females had significantly shorter femoral tunnels than males in both Chinese and Caucasian (P < 0.001). The overall invasion rate of the posterior cortex and medial femoral condyle were 32.6% and 7.4% for Chinese; 31.0% and 7.4% for Caucasians, respectively.ConclusionTo reduce risks of injury to anatomical structures, such as the LFAS, posterior cortex and medial femoral condyle, specific angle combinations of 30°/45°, 45°/30°, 45°/45°, 45°/60°, 60°/30°, 60°/45° and 60°/60° should be used when creating the femoral tunnel in single-bundle ACLR. The selected drilling angles are critical for optimizing femoral tunnel placement.

Ameliorative effects of aqueous extract of Colocasia esculenta leaf against lipopolysaccharide-induced prefrontal cortex damage in mice

IntroductionThe prefrontal cortex (PFC), crucial for cognition and memory, occupies a third of the cerebral cortex. This study investigated the protective effects of aqueous extract of Colocasia esculenta leaf (AECEL) against lipopolysaccharide (LPS)-induced PFC damage in mice.Methods42 male Swiss albino mice (18–22 g) were divided into six groups. Group A: healthy controls. Groups B-F received daily intraperitoneal LPS injections (0.5 mg/kg) for seven days. Group B: received distilled water, (2 ml) subsequently. Groups C-E: AECEL at 400, 600, and 800 mg/kg, respectively. Group F: donepezil (DPZ, 2.5 mg/kg) by oral gavage. All treatments continued for 28 days.ResultsLPS exposure significantly increased brain oxidative stress markers and reduced antioxidant enzymes compared to controls (p < 0.05). AECEL and DPZ administration significantly reduced brain oxidative stress markers and reduced antioxidant enzymes, as well as tumor necrosis factor-α and interleukin-6 levels (p < 0.05) compared to LPS ONLY group. Y-maze testing revealed decreased alternation (%) in the LPS group compared to controls (p < 0.05). Based on Y-maze performance, AECEL at 400 mg/kg emerged as the most effective dose, significantly improving alternation (%) compared to both LPS and LPS + DPZ groups (p < 0.05). Bielschowsky staining showed senile plaques and neurofibrillary tangles in the LPS group.ConclusionLPS induced PFC damage. Among the tested doses, AECEL at 600 mg/kg demonstrated the most effective improvement in cognitive function, memory, and anxiety-like behaviors as measured by the Y-maze test.

Investigation of the Effects of White Tea Against Cerebral Cortex Damage Induced by Cisplatin

Investigation of the Effects of White Tea Against Cerebral Cortex Damage Induced by Cisplatin

Ameliorating Effect of 10-Dehydrogingerdione against Cerebral Cortex Damage caused by Tramadol in Adult Male Albino Rats (Histological and Immunohistochemical study)

Ameliorating Effect of 10-Dehydrogingerdione against Cerebral Cortex Damage caused by Tramadol in Adult Male Albino Rats (Histological and Immunohistochemical study)

In-silico analysis of ethanol peel extract of Citrus sinensis on mercury chloride-induced prefrontal cortex damage in Wistar rat

This study evaluated the effect of ethanolic extract of Citrus sinensis peel on mercury chloride-induced changes in the prefrontal cortex of adult Wistar rats. Twenty-five Wistar rats were purchased and divided into five groups containing five animals in each group. Group 1 was administered with distilled water, Group 2, Group 3, Group 4, and Group 5 were administered with 5 mg/kg of mercury chloride only, 5 mg/kg of mercury chloride and 140 mg/kg Silymarin, 5 mg/kg mercury chloride and 1000 mg/kg of ethanoic extract of orange peel, and 5 mg/kg mercury chloride and 1500 mg/kg of ethanoic extract of orange peel. All administration was done orally and the administration lasted for 14 days. The animals were sacrificed humanely using 75 mg/kg ketamine intraperitoneally and prefrontal was dissected out. Part was homogenized in 0.1M phosphate buffered saline for the estimation of superoxide dismutase (SOD), and catalase (CAT) activities, and Malondialdehyde (MDA) level and the other part was fixed by immersion in 10 neutral buffered formal-saline for histological evaluation. The chemical structure of sixteen compounds from Citrus sinensis peel obtained from GC-MS analysis reported in the literature were retrieved from the PubChem compound database and the crystal structure of human peroxisome proliferator- activated receptor gamma (PPARγ; PDB:ID: 2P4Y) reported to increase the expression of catalase gene, human extracellular copper-zinc superoxide dismutase enzyme (PDB ID: 2JLP) and mammalian 15-lipoxygenase - 1 enzyme (PDB ID: 2P0M) responsible for the production of lipid peroxidation were retrieved from the PDB database. Ligands and protein preparation, docking and MM-GBSA relative binding free energy calculation were done in Maestro 2023.1. Data obtained was analyzed using the IBM SPSS (version 25) using one-way ANOVA and p-value &lt; 0.05 was considered statistically significant. The results indicate that the MDA level in control Group(13.29±1.183 μmol) is statistically significantly lower compared to the Group 2 (21.88±1.96 μmol), group 3 (27.44±3.52 μmol), Group 4 (22.20±1.16 μmol) and Group 5 (25.40±3.13 μmol). No statistically significant difference was observed in SOD activity. The CAT activities in control group (53.51±6.83 nmol/ml) was statistically significantly lower compared to the group 2 (26.21±3.70 nmol/ml), Group 3 (27.17±5.32 nmol/ml), Group 4 (25.30±4.24 nmol/ml) and Group5 (26.59±4.22 nmol/ml).The present study suggests, ethanolic extract of Citrus sinensis peel have protective effects on mercury-induced changes in prelimbic part of the prefrontal cortex of adult Wistar rats.

Biochemical and histological analysis of ethanol peel extract of Citrus sinensis on mercury chloride-induced prefrontal cortex damage in Wistar rats

Mercury is one of the heavy metals which is found extensively in many environmental and certain occupational settings. It is the third most dangerous heavy metal and its toxicity causes serious risks to health through unfavorable pathological and biochemical effects. Sweet orange is the fruit of the citrus species (Citrus sinensis) in the family Rutaceae.. Over time there has been increasing interest in the utilization of these peels for both nutritional and medicinal purposes. Studies have reported the antioxidant potential of orange peel oil in laboratory rodents, indicating its protective effect against oxidative stress-mediated ailments. The study evaluated the effect of ethanolic extract of Citrus sinensis peel on mercury chloride-induced changes in the prefrontal cortex of adult Wistar rats. Twenty-five Wistar rats were purchased and divided into five groups containing five animals in each group. Group 1 was administered with distilled water, Group 2, Group 3, Group 4, and Group 5 were administered with 5 mg/kg of mercury chloride only, 5 mg/kg of mercury chloride and 140 mg/kg Silymarin, 5 mg/kg mercury chloride and 1000 mg/kg of ethanoic extract of orange peel, and 5 mg/kg mercury chloride and 1500 mg/kg of ethanoic extract of orange peel. All administration was done orally and the administration lasted for 14 days. The animals were sacrificed humanely using 75 mg/kg ketamine intraperitoneally and prefrontal was dissected out. Part was homogenized in 0.1M phosphate buffered saline for the estimation of superoxide dismutase (SOD), and catalase (CAT) activities, and Malondialdehyde (MDA) level and the other part was fixed by immersion in 10 neutral buffered formal-saline for histological evaluation. The results indicate that the MDA level in control Group(13.29±1.183 μmol) is statistically significantly lower compared to the Group 2 (21.88±1.96 μmol), group 3 (27.44±3.52 μmol), Group 4 (22.20±1.16 μmol) and Group 5 (25.40±3.13 μmol). No statistically significant different that was observed in SOD activity. It CAT activities in control group (53.51±6.83 nmol/ml) is statistically significantly lower compared to the group 2 (26.21±3.70 nmol/ml), Group 3 (27.17±5.32 nmol/ml), Group 4 (25.30±4.24 nmol/ml) and Group5 (26.59±4.22 nmol/ml). Protective role of the extract was observed from the histological evaluation. This study suggests that ethanolic extract of Citrus sinensis peel have protective effects on mercury-induced changes in prelimbic part of the prefrontal cortex of adult Wistar rats.

CD36-mediated ROS/PI3K/AKT signaling pathway exacerbates cognitive impairment in APP/PS1 mice after noise exposure

There is an association between noise exposure and cognitive impairment, and noise may have a more severe impact on patients with Alzheimer's disease (AD) and mild cognitive impairment; however, the mechanisms need further investigation. This study used the classic AD animal model APP/PS1 mice to simulate the AD population, and C57BL/6J mice to simulate the normal population. We compared their cognitive abilities after noise exposure, analyzed changes in Cluster of Differentiation (CD) between the two types of mice using transcriptomics, identified the differential CD molecule: CD36 in APP/PS1 after noise exposure, and used its pharmacological inhibitor to intervene to explore the mechanism by which CD36 affects APP/PS1 cognitive abilities. Our study shows that noise exposure has a more severe impact on the cognitive abilities of APP/PS1 mice, and that the expression trends of differentiation cluster molecules differ significantly between C57BL/6J and APP/PS1 mice. Transcriptomic analysis showed that the expression of CD36 in the hippocampus of APP/PS1 mice increased by 2.45-fold after noise exposure (p < 0.001). Meanwhile, Western Blot results from the hippocampus and entorhinal cortex indicated that CD36 protein levels increased by approximately 1.5-fold (p < 0.001) and 1.3-fold (p < 0.05) respectively, after noise exposure in APP/PS1 mice. The changes in CD36 expression elevated oxidative stress levels in the hippocampus and entorhinal cortex, leading to a decrease in PI3K/AKT phosphorylation, which in turn increased M1-type microglia and A1-type astrocytes while reducing the numbers of M2-type microglia and A2-type astrocytes. This increased neuroinflammation in the hippocampus and entorhinal cortex, causing synaptic and neuronal damage in APP/PS1 mice, ultimately exacerbating cognitive impairment. These findings may provide new insights into the relationship between noise exposure and cognitive impairment, especially given the different expression trends of CD molecules in the two types of mice, which warrants further research.

Clinicopathologic and Neuroimaging Correlations of Nonverbal Oral Apraxia in Patients With Neurodegenerative Disease.

Nonverbal oral apraxia (NVOA) is the inability to plan, sequence, and execute voluntary oromotor movements in the absence of weakness. In the context of neurodegenerative disease, it remains unclear whether it is linked to a specific underlying pathologic, clinical, or neuroimaging finding. Thus, we aimed to assess the clinicopathologic and neuroimaging associations of NVOA. We conducted a retrospective study of autopsy-confirmed patients previously assessed through an NVOA evaluation tool with a previously published cutpoint to screen for NVOA. We compared demographic and clinical characteristics and postmortem pathology between those who developed NVOA and those who did not. We also compared clinicopathologic characteristics in mild vs greater than mild NVOA and early vs late-emerging NVOA. SPM12 was used to assess patterns of gray matter loss in NVOA vs non-NVOA with age and sex included as covariates. A total of 104 patients (median age at symptom onset 63 years, 43% female) were included in the study. 63 (60.6%) developed NVOA. NVOA appeared at a median of 4.3 years from symptom onset. 29% developed NVOA within the first 3 years. Primary progressive apraxia of speech and the nonfluent variant of primary progressive aphasia were the most common baseline diagnoses in the NVOA group while progressive supranuclear palsy (PSP) syndrome and logopenic progressive aphasia (LPA) were the most common in patients without NVOA. Atrophy of the left lateral and medial posterior frontal cortex was related to NVOA. The most common pathologies associated with NVOA were PSP (36.5%) and corticobasal degeneration (CBD) (33.3%). In patients without NVOA, PSP (26.8%) and other pathologies (26.8%) were the most frequent. 11% of patients with NVOA had persistently mild NVOA and were more likely to have baseline diagnoses of LPA, PSP syndrome, or semantic dementia. The most frequent pathologies in this group were Alzheimer disease and PSP. The pathologic associations of greater than mild NVOA were CBD and PSP. NVOA is present in several clinical syndromes. It is most associated with PSP and CBD. NVOA is a manifestation of left lateral and medial posterior frontal cortex damage rather than a particular pathology.

Pretreatment with 4-methylumbilliferon improves anxiety-like behaviors and memory impairment in stressed rats via modulation of neuronal cell death and oxidative stress

This work was done to investigate the ameliorating impact of 4-methylumbilliferon (4-MU) on spatial learning and memory dysfunction and restraint stress (STR)-induced anxiety-like behaviors in male Wistar rats and the underlying mechanisms. Thirty-two animals were assigned into 4 cohorts: control, 4-MU, STR, and STR+4-MU. Animals were exposed to STR for 4 h per day for 14 consecutive days or kept in normal conditions (healthy animals without exposure to stress). 4-MU (25 mg/kg) was intraperitoneally administered once daily to STR rats before restraint stress for 14 consecutive days. The behavioral tests were performed through Morris water maze tests and elevated-plus maze to examine learning/memory function, and anxiety levels, respectively. The levels of the antioxidant defense biomarkers (GPX, SOD) and MDA as an oxidant molecule in the brain tissues were measured using commercial ELISA kits. Neuronal loss or density of neurons was evaluated using Nissl staining. STR exposure could cause significant alterations in the levels of the antioxidant defense biomarkers (MDA, GPX, and SOD) in the prefrontal cortex and hippocampus, induce anxiety, and impair spatial learning and memory function. Treatment with 4-MU markedly reduced anxiety levels and improved spatial learning and memory dysfunction via restoring the antioxidant defense biomarkers to normal values and reducing MDA levels. Moreover, more intact cells with normal morphologies were detected in STR-induced animals treated with 4-MU. 4-MU could attenuate the STR-induced anxiety-like behaviors and spatial learning and memory dysfunction by reducing oxidative damage and neuronal loss in the prefrontal cortex and hippocampus region. Taken together, our findings provide new insights regarding the potential therapeutic effects of 4-MU against neurobehavioral disorders induced by STR.

ISRIB ameliorates spatial learning and memory impairment induced by adolescent intermittent ethanol exposure in adult male rats

Alcohol exposure in adolescence is considered a major cause of cognitive impairments later in life including spatial learning and memory. Integrated stress response (ISR), a program of conservative translation and transcription, is crucial in synaptic plasticity and memory. Although previous studies have elucidated ISR in different brain areas involved in learning and memory disorders, the impact of ISR on learning and memory following adolescent alcohol exposure remains unclear. Here, we demonstrated that adolescent intermittent ethanol (AIE) exposure caused spatial learning and memory impairment, combined with neuronal damage in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (HIP) in adult rats. Moreover, integrated stress response inhibitor (ISRIB) administration not only improved spatial learning and memory impairment and neuronal damage but also inhibited the endoplasmic reticulum stress (ER) and reversed changes in synaptic proteins. These findings suggested that ISRIB ameliorates AIE exposure-induced spatial learning and memory deficits by improving neural morphology and synaptic function through inhibiting ER stress signaling pathway in the mPFC, NAc and HIP in adulthood. Our findings may enhance comprehension of cognitive function and neuronal effects of adolescent ethanol exposure and ISRIB treatment may be an underlying potential option for addressing alcohol-induced learning and memory deficits.

Speech-language performance and comorbid disorders in children with perisylvian syndrome induced by viral encephalitis.

Viral encephalitis is one of the main causes of the perisylvian syndrome, which can cause damage to children's language-speech, feeding, and swallowing functions. Comprehensive assessment of language-speech and swallowing function and comorbidity research on these children will help children's rehabilitation workers to better understand the disease and strengthen the systematic management of comorbid disorders. To describe speech and language pathology and the occurrence of comorbid disorders in children with perisylvian syndrome induced by viral encephalitis. Twenty-two children with acquired perisylvian syndrome were recruited in this study. Language and speech functions, including oral motor function, swallowing function, language ability, and dysarthria were assessed in these patients. Craniocerebral magnetic resonance imaging (MRI), electroencephalogram examination, and intelligence evaluation were performed to determine brain lesions and comorbid disorders. All children exhibited different degrees of oral movement, dysphagia, and speech and language disorders. There was a significant difference between expressive and receptive language ability (P<0.05). There were 10, 8, and 12 children who had an intellectual disability, limb disability, and epilepsy, respectively. In addition to the damage of the peri-tegmental cortex found in MRI, thalamus lesions occurred in 19 cases and white matter involvement in six cases. Children with acquired perisylvian syndrome caused by viral encephalitis are characterized by persistent pseudobulbar dysfunction, speech and language impairment, and orofacial diplegia. They have a high probability of secondary epilepsy and are prone to motor and cognitive impairment, which need systematic management.

Efficacy of stem cells versus microvesicles in ameliorating chronic renal injury in rats (histological and biochemical study)

Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1β, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.

Jiawei Bai-Hu-decoction ameliorated heat stroke-induced brain injury by inhibiting TLR4/NF-κB signal and mitophagy of glial cell

Ethnopharmacological relevanceJiawei Bai-Hu-Decoction (JWBHD), a prescription formulated with seven traditional Chinese medicinal material has demonstrated clinical efficacy in mitigating brain injury among heat stroke (HS) patients. Aim of the studyThis study aimed to evaluate the therapeutic efficacy of JWBHD on rat model of HS and to explore its therapeutic mechanisms by integrating network pharmacology and pharmacodynamic methodologies, which major components were analyzed by using UPLC-MS/MS. Materials and methodsThe network pharmacology analysis was firstly conducted to predict the potential active ingredients and therapeutic targets of JWBHD. The anti-HS effectiveness of JWBHD was then evaluated on rats experienced HS. Rat brain tissues were harvested for a comprehensive array of experiments, including Western blot, PCR, H&E staining, Nissl staining, ELISA, transmission electron microscope, flow cytometry and immunofluorescence to validate the protective effects of JWBHD against HS-induced brain damage. Furthermore, the inhibitory effects of JWBHD on TLR4/NF-κB signal and mitophagy of glial were further verified on HS-challenged F98 cell line. Finally, the chemical compositions of the water extract of JWBHD were analyzed by using UPLC-MS/MS. ResultsNetwork pharmacology has identified fifty core targets and numerous HS-related signaling pathways as potential therapeutic targets of JWBHD. Analysis of protein-protein interaction (PPI) and GO suggests that JWBHD may suppress HS-induced inflammatory signals. In experiments conducted on HS-rats, JWBHD significantly reduced the core temperature, restored blood pressure and alleviated neurological defect. Furthermore, JWBHD downregulated the counts of white blood cells and monocytes, decreased the levels of inflammatory cytokines such as IL-1β, IL-6 and TNF-α in peripheral blood, and suppressed the expression of TLR4 and NF-κB in the cerebral cortex of HS-rats. Besides, JWBHD inhibited the apoptosis of cortical cells and mitigated the damage to the cerebral cortex in HS group. Conversely, overactive mitophagy was observed in the cerebral cortex of HS-rats. However, JWBHD restored the mitochondrial membrane potential and downregulated expressions of mitophagic proteins including Pink1, Parkin, LC3B and Tom20. JWBHD reduced the co-localization of Pink1 and GFAP, a specific marker of astrocytes in the cerebral cortex of HS-rats. In addition, the inhibitory effect of JWBHD on TLR4/NF-κB signaling and overactive mitophagy were further confirmed in F98 cells. Finally, UPLC-MS/MS analysis showed that the main components of JWBHD include isoliquiritigenin, liquiritin, dipotassium glycyrrhizinate, ginsenoside Rb1, ginsenoside Re, etc. ConclusionsJWBHD protected rats from HS and prevented HS-induced damage in the cerebral cortex by suppressing TLR4/NF-κB signaling and mitophagy of glial.

Diallyl trisulfide regulates PGK1/Nrf2 expression and reduces inflammation to alleviate neurological damage in mice after traumatic brain injury

BackgroundDiallyl trisulfide (DATS) has a direct antioxidant capacity and emerges as a promising neuroprotective agent. This study was designed to investigate the role of DATS in traumatic brain injury (TBI). MethodsTBI mouse models were established using the controlled cortical impact, followed by DATS administration. The effects of DATS on neurological deficit, brain damage, inflammation and phosphoglycerate kinase 1 (PGK1) expression were detected using mNSS test, histological analysis, TUNEL assay, enzyme-linked immunosorbent assay and immunofluorescence. PC12 cells were subjected to H2O2-induced oxidative injury after pre-treatment with DATS, followed by cell counting kit-8 assay, flow cytometry and ROS production detection. Apoptosis-related proteins and the PGK1/nuclear factor erythroid-2 related factor 2 (Nrf2) pathway were examined using Western blot. ResultsDATS ameliorated the cerebral cortex damage, neurological dysfunction and apoptosis, as well as decreased PGK1 expression and expressions of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in mice after TBI. DATS also enhanced viability, blocked apoptosis and inhibited ROS production in H2O2-induced PC12 cells. DATS downregulated Cleaved-Caspase3, Bax and PGK1 levels, and upregulated Bcl-2 and Nrf2 levels in TBI mouse models and the injured cells. ConclusionDATS regulates PGK1/Nrf2 expression and inflammation to alleviate neurological damage in mice after TBI.

Temporal organization of narrative recall is present but attenuated in adults with hippocampal amnesia.

Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well-established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non-brain-injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non-brain-injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal-dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment.

KeYu ShuShen Granule alleviates symptoms of depression by targeting the mTOR pathway in a rat model of depression induced by chronic unpredictable mild stress

BackgroundKeYu ShuoShen Granules (KSG) is a traditional Chinese medicine formula with radix bupleuri as the kingpin, which is widely used in the treatment of depression, but its exact mechanism of action is not yet fully understood. The aim of this study is to investigate the therapeutic mechanisms of KSG in a model of depression in rats. MethodsRats were equally divided into 5 groups including control, model, fluoxetine, KSG at high and low doses, chronic unpredictable mild stress combined with solitary rearing for 28 days was used to prepare a rat model of depression followed by 14 days of continuous gavage and modelling, and the antidepressant effects of KSG were analyzed using behavioral tests, proteomic techniques and pharmacological methods. ResultsAfter KGS treatment, the body weight, Sucrose Preference of the model rats increased significantly, and their motor and learning memory abilities were significantly improved in the open field test and Morris water maze (P<0.01 or P<0.05); At the same time, proteomics revealed a total of 7 differential proteins, 3 differential pathways, including Agps, Eif4e2, Pter, Sys1, Rgcc, Polr1d and Npy1r, mTOR signalling pathway, insulin signalling pathway, and human papillomavirus infection; the expression of p-mTOR, mTOR, and Eif4e2 was significantly up-regulated after drug administration (P<0.01 or P<0.05), and neuronal damage in the cerebral cortex was significantly restored. ConclusionKSG improved depression symptoms in model rats by modulating protein synthesis processes involved in the mTOR pathway and Eif4e2, producing a combined effect on the nervous system. This finding provides new theoretical support and a mechanistic explanation for the use of KSG in the treatment of depression.