Bacterial meningitis represents a devastating inflammatory disease of the central nervous system (CNS), characterized by the invasion of pathogens across the blood-brain barrier (BBB) and subsequent dysregulated immune responses. Key inflammatory mechanisms include pathogen recognition by microglial TLRs and NLRP3, neutrophil infiltration, and cytokine storms such as IL-1β and TNF-α, leading to BBB disruption, cerebral edema, and neuronal injury. Despite antimicrobial therapy, excessive inflammation often results in neurological sequelae. Emerging strategies target immunomodulation through inflammasome inhibitors and BBB preservation using nanoparticle drug delivery to mitigate inflammation-driven CNS damage. This review focuses on the intricate interplay between bacterial virulence factors and neuroinflammatory cascades, with particular emphasis on Streptococcus pneumoniae as a model pathogen. By integrating recent advances in molecular pathogenesis and translational immunology, this review provides a framework for developing precision therapies to mitigate inflammation-mediated CNS damage in bacterial meningitis.

Parkinson’s disease (PD) imposes a significant health burden among older adults and may be related to zinc and ring finger 2 (ZNRF2)—a member of the ubiquitination family. To investigate the role and mechanism of action of ZNRF2 in the regulation of mammalian target of rapamycin (mTOR)-mediated neuroinflammation in a mouse model of PD. Healthy mice were injected intraperitoneally with either saline (control) or MPTP 30 mg/kg. Mouse behavior was tested using rotarod and open field tests. The distribution and expression of tyrosine hydroxylase (TH) were determined by immunoblotting and immunohistochemistry. Inflammatory factors were evaluated using immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence assay. Compared with mice injected with saline, MPTP-treated mice showed significantly impaired locomotor activity, a significant decrease in the number of TH neurons, and a markedly altered morphology. ZNRF2 expression was significantly increased in the mesencephalon of MPTP-treated mice compared to that in control mice. ZNRF2 knockdown exacerbated motor dysfunction, accelerated dopamine neuron degeneration and death, increased the levels of pro-inflammatory factors (e.g., interleukin (IL)-1β, IL-6), and suppressed the expression of anti-inflammatory factors (e.g., IL-4, IL-10) in the central nervous system of MPTP-treated mice, with more pronounced activation of microglia and astrocytes. ZNRF2 knockdown significantly elevated phosphorylated mTOR protein levels after MPTP treatment; subsequently, phosphorylated mTOR protein levels were inhibited; dyskinesia and dopamine neuronal damage were significantly ameliorated, and neuroinflammation was suppressed in PD mice. ZNRF2 regulates the pathogenesis of MPTP-induced PD in mice via mechanisms related to mTOR-mediated neuroinflammation.

This study investigates the effects of adding whey protein powder and Bifidobacterium quadruplex live bacterial tablets to enteral nutrition on nutritional indicators, complications, and prognosis in neurological ICU patients. Between April 2022 and December 2023, 100 patients requiring enteral nutrition in our hospital’s Neurology ICU were randomly assigned to four groups (25 each): EN1 (enteral nutrition only), EN2 (enteral nutrition + Bifidobacterium), EN3 (enteral nutrition + Bifidobacterium + whey protein), and EN4 (enteral nutrition + whey protein). Nutritional indicators (albumin, total protein, prealbumin), complication rates (diarrhea, constipation, gastric issues), prognosis indicators (hospital stay, ventilator use, lung infections, antibiotic use), and APACHE II scores were compared. This study has been approved by the Ethics Committee of the Affiliated Hospital of Zunyi Medical University, NO: KLL-2021-112. We confirm that all experiments were performed in accordance with relevant guidelines and regulations. After 7 days, EN3 and EN4 groups showed significantly improved nutritional indicators compared to EN1, with EN3 outperforming EN2. Diarrhea and gastric mucosal bleeding were less frequent in EN2 and EN3 compared to EN1 and EN4. APACHE II scores improved significantly in EN3 and EN4 post-treatment. EN3 had the lowest pulmonary infection rate and reduced antibiotic use, but hospitalization time differences were not significant across groups. Metabolic indicators showed no significant differences between groups. Supplementing enteral nutrition with whey protein powder and Bifidobacterium quadruplex improves nutritional status, reduces gastrointestinal complications, and enhances prognosis in critically ill neurological patients. Trial registration: ChiCTR2300079322, (30/12/2023); Website where it was obtained: https://www.chictr.org.cn/bin/home

Epilepsy is one of the common clinical disorders with comorbid anxiety and depression that severely affects their quality of life and increases their suicidality, while screening for anxiety and depression currently lacks objective identifiers. This study aimed to analyze the characteristics of the electroencephalogram (EEG) power spectrum in patients with epilepsy with comorbid anxiety and depression, utilizing resting EEG data. Resting EEG data were collected under standard conditions from two groups: patients with epilepsy comorbid with anxiety and depression (n = 42) and patients without comorbidities (n = 45). EEG power was calculated using data processing with EEGLAB and MATLAB. This study compared the absolute and relative powers of the δ, θ, α, β, and γ frequency bands, as well as the values of (δ + θ)/(α + β), between the two groups. Additionally, the correlation between the EEG power of each frequency band and anxiety and depression scores was analyzed. 1) Among individuals with epilepsy comorbid with anxiety and depression, lower absolute power of δ, α, and θ at specific sites was observed (P < 0.05), along with lower relative power of θ at certain sites (P < 0.05). Conversely, higher relative power of β and γ at specific sites was noted in those with comorbidities (P < 0.05). 2) There was no statistically significant difference in the values of (δ + θ)/(α + β) between the two groups (P > 0.05). 3) Depression scores exhibited a negative correlation with θ absolute power at the T3 and T4 sites (P < 0.05), while showing a positive correlation with β relative power at the C4 and T6 sites (P < 0.05). Anxiety scores displayed a positive correlation with β relative power at the F4, C3, C4 and T6 sites and γ relative power at F8 site (P < 0.05). The findings suggest that comorbid anxiety and depression may impact resting EEG power spectra in individuals with epilepsy, particularly in regions exhibiting altered network connectivity. Furthermore, a positive correlation was observed between anxiety and depression scores and β relative power in the right central and right posterior temporal regions, indicating potential screening utility.

Cerebrovascular diseases, particularly ischemic stroke, are a leading cause of global disability. Effective management of ischemia-reperfusion injury is crucial in stroke treatment. Emodin, known for its anti-inflammatory and neuroprotective properties, has been shown to protect against ischemia-reperfusion injury by modulating pyroptosis. However, the molecular mechanisms underlying its effects in cerebral ischemia-reperfusion injury are not well understood. This study aims to investigate the neuroprotective mechanisms of Emodin in ischemic stroke. SD rats were randomly assigned to different groups: control, sham, model, and Emodin intervention groups with varying dosages. Cerebral ischemia-reperfusion injury was induced using the middle cerebral artery occlusion (MCAO) method, and Emodin (10 mg/kg, 20 mg/kg, 40 mg/kg) was administered intraperitoneally. Neurological deficits were evaluated using the modified Neurological Severity Score (mNSS), and infarct volume was assessed via TTC staining. Pathomorphological changes were observed using HE staining. Protein expression levels associated with pyroptosis, including NLRP3, Caspase 1, and GSDMD, were analyzed by Western blotting and immunofluorescence. The levels of IL-1β and IL-18 were measured using ELISA (Caspase 1 indicates cleaved Caspase 1, GSDMD indicates the active pro-forms of GSDMD, used throughout). Emodin exhibits significant beneficial effects in improving neurological deficits caused by cerebral ischemia-reperfusion injury. It effectively reduces the ratio of infarct volume, alleviates cytopathic damage, and suppresses the expression of pyroptosis-related proteins, including NLRP3, Caspase 1, Caspase 1, and GSDMD. Furthermore, Emodin decreases the levels of pro-inflammatory cytokines IL-1β and IL-18, thus attenuating the inflammatory response. The expression of pyroptosis-related proteins is upregulated in rats after cerebral ischemia-reperfusion injury. Emodin demonstrates neuroprotective effects against cerebral ischemia-reperfusion injury in rats, potentially by modulating the expression of pyroptosis-related proteins mediated through the Caspase 1-GSDMD axis.

Parkinson’s disease (PD) is a common neurodegenerative disease in the older adults. The main pathological change in PD is the degenerative death of dopamine (DA) neurons in the midbrain substantia nigra, which causes a significant decrease in the DA content of the striatum. However, the exact etiology of this pathological change remains unclear. Genetic factors, environmental factors, aging, and oxidative stress may be involved in the degenerative death of dopaminergic neurons in PD. Pharmacological treatment using levodopa (l-DOPA) remains the main treatment for PD. Most patients with PD consuming l-DOPA for a long time usually develop levodopa-induced dyskinesia (LID) after 6.5 years of use, and LID seriously affects the quality of life and increases the risk of disability. Recently, studies have revealed that cerebral iron deposition may be involved in LID development and that iron deposition has neurotoxic effects and accelerates disease onset. However, the relationship between cerebral iron deposition and LID remains unclear. Herein, we reviewed the mechanisms by which iron deposition may be associated with LID development, which are mainly related to oxidative stress, neuroinflammation, and mitochondrial and lysosomal dysfunction. Using iron as an important target, the search and development of safe and effective brain iron scavengers, and thus the alleviation and treatment of LID, has a very important scientific and clinical value, as well as a good application prospect.

Cerebrovascular diseases (CVDs) have become a global public health problem and ischemia‑reperfusion injury, the major cause of neurological impairment exacerbation, is closely related to excitotoxicity. The present study aimed to investigate the effects of changes in heat shock protein (HSP)90β expression and verify whether HSP90β regulates EAAT2 expression in a cerebral ischemia‑reperfusion injury model. Healthy adult Sprague‑Dawley (SD) male rats were used to establish a control group, sham‑operated group, middle cerebral artery occlusion (MCAO) group, empty virus group and lentivirus group. A model of cerebral ischemia‑reperfusion was established using the MCAO method. Lentivirus construction and injection were used to interfere with the expression of HSP90β. The modified neurological severity score was used to assess neurological deficits. Triphenyltetrazolium chloride staining was used to detect infarct areas. Immunofluorescence was used to detect HSP90β expression localization and the expression levels of HSP90β and EAAT2 were determined using western blotting and reverse transcription‑quantitative PCR. An MCAO model was successfully established and it was found that HSP90β, but not HSP90α, was upregulated after MCAO. HSP90β expression coincided with astrocyte markers in the ischemic penumbra area, while no expression was observed in microglia. Inhibition of HSP90β expression improved neurological deficits and alleviated brain injury by increasing EAAT2 expression. These results suggested that HSP90β is involved in the process of cerebral ischemia‑reperfusion injury in rats and that inhibition of HSP90β expression increases EAAT2 levels, conferring a neuroprotective effect in MCAO model rats.

Parkinson's disease (PD) is a common degenerative disease of the central nervous system that is characterized by movement disorders and non-motor symptoms (NMSs). The associated NMSs primarily include neuropsychiatric symptoms, autonomic dysfunction, sleep-wake disorders, pain, fatigue, and hyposmia. These NMSs can occur at any stage of PD, especially before the onset of motor symptoms, and may affect a patient's quality of life more than motor symptoms. Although PD is most commonly diagnosed in people over 65 years, some patients exhibit symptom onset before the age of 50, which is clinically known as early-onset Parkinson's disease (EOPD). The high heterogeneity and incidence of EOPD-associated NMSs can lead to the misdiagnosis of EOPD as other neurodegenerative diseases. In this review, we discuss the research progress related to NMSs in patients with EOPD, focusing on neuropsychiatric disorders, autonomic dysfunction, sleep disorders, and sensory impairment, and outline the association of NMSs with different genotypic alterations, with the aim of providing assistance in the clinical management of patients.

Objective To analyze the risk factors for dismal prognosis in patients with cryptococcal meningitis and construct a prediction scoring system Nomogram model. Methods A total of 100 patients with cryptococcal meningitis who treated with anticryptococcal therapy admitted to Affiliated Hospital of Zunyi Medical University from January 2010 to August 2022 were selected. The patients were divided into favorable prognosis group (n = 19) and dismal prognosis group (n = 81) according to the results of cerebrospinal fluid (CSF) cryptococcal culture during hospitalization and clinical symptoms and signs at the time of discharge. Risk factors were screened by using univariate and multivariate stepwise Logistic regression analyses. A Nomogram model was constructed based on the risk factors, the receiver operating characteristic (ROC) curve and calibration curves of the model were plotted, and Hosmer - Lemeshow goodness-of-fit test was performed. Results The proportion of patients in the dismal prognosis group with Nutritional Risk Screening 2002 (NRS 2002) score (Z = - 3.898, P = 0.000), CSF pressure > 250 mm H2O (χ2 = 9.512，P = 0.002) and duration of antifungal treatment < 14 d (χ2 = 17.847，P = 0.000) on admission were higher than those in the favorable prognosis group, and the blood routine red blood cell count (t = - 2.802, P = 0.006) and lymphocyte count (Z = - 2.878, P = 0.004), plasma albumin (t = - 4.332, P = 0.000), and the proportion of amphotericin B application (χ2 = 4.597, P = 0.032) were lower than those in the favorable prognosis group. Logistic regression analysis showed the admission high NRS 2002 score (OR = 3.258, 95%CI: 1.337-7.940; P = 0.009), CBF pressure > 250 mm H2O (OR = 0.108, 95%CI: 0.018-0.659; P = 0.016), and the duration of antifungal treatment < 14 d (OR = 0.092, 95%CI: 0.011-0.742; P = 0.025) were risk factors for dismal prognosis of cryptococcal meningitis. A Nomogram model was constructed based on the above 3 risk factors, and the area under the ROC curve was 0.927 (95%CI: 0.873-0.980, P = 0.000), which predicted a cut - off value of 53.50 points for dismal prognosis in cryptococcal meningitis; the calibration curve (with good consistency), and the Hosmer-Lemeshow goodness-of-fit test (χ2 = 2.694, P = 0.912) indicated that the model had good discrimination, calibration and stability. Conclusions Patients with cryptococcal meningitis with a high NRS 2002 score, CSF pressure > 250 mm H2O, and antifungal treatment < 14 d had a dismal prognosis, and the Nomogram model constructed accordingly has a high predictive value of dismal prognostic risk.

Cerebral toxoplasmosis is a common opportunistic infectious disease in immunocompromised patients that usually involves the central nervous system. The clinical features and neuroimaging findings of cerebral toxoplasmosis are often similar to brain abscess and tuberculoma. We report a case of hepatitis C with cerebral toxoplasmosis, with the aim of enhancing understanding of the imaging manifestations of cerebral toxoplasmosis and thereby improving the differential diagnosis of brain space-occupying lesions.

This study aimed to examine the mediating role of anxiety and depression in the relationship between coping styles and life satisfaction among frontline medical workers during the COVID-19 pandemic. Five hundred and fourteen frontline medical workers from Zunyi were recruited to complete questionnaires, including the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Satisfaction with Life Scale (SWLS), and Simplified Coping Style Questionnaire (SCSQ). SPSS 24.0 was used to measure the characteristics of anxiety, depression, life satisfaction, and coping styles. We found that the prevalence rates of anxiety and depression among study participants were 22.57% and 18.29%, respectively. Besides, anxiety was positively correlated with depression; anxiety and depression were positively correlated with passive coping style but negatively correlated with life satisfaction and active coping style; life satisfaction was positively correlated with active coping style and negatively correlated with passive coping style (all p < 0.001). Moreover, anxiety and depression mediated the relationship between coping styles and life satisfaction. Anxiety accounted for 18.6% of the effect of active coping style and 35.48% of the effect of passive coping style on life satisfaction. Depression accounted for 48.84% of the effect of active coping style and 67.74% of the effect of passive coping style on life satisfaction. The present study provides novel insights into the effect of subclinical anxiety and depression on frontline medical workers in the pandemic area. Anxiety and depression yielded a mediating effect on the relationship between coping styles and life satisfaction.

Compound porcine perebroside and ganglioside injection (CPCGI) was used to treat stroke. The study was initiated because of the high incidence of low-does CPCGI use in our area. However, no research has confirmed the effectiveness of CPCGI below the standard dose. Therefore, the aim of this study was to provide a reference for the clinical selection of different dose treatments. We collected ischemic stroke patients and divided them into three groups (low-dose group: Group A = 4 mL, Group B = 6 mL, standard-dose group: Group C = 10 mL). The modified Rankin Scale (mRS) scores, the National Institutes of Health Stroke Scale (NIHSS) scores, and the Barthel Index (BI) scores were performed before treatment and 14 days and 90 days post CPCGI treatment. For 90 days, the primary outcomes were calculated including the degree of disability, neurological recovery, and activities of daily living. All data were compared between pretherapy and posttreatment and among groups. NIHSS, mRS and BI scores improved on 14 and 90 days in each group. Group B and C improved than Group A on 14 and 90 days. The difference between groups B and C was not statistically significant. On 90 days, there were differences in the degree of disability, the recovery of neurological function, and the ability of daily living among groups. No drug-related adverse reactions occurred in the groups. Although 4 or 6 mL CPCGI had some neuroprotective effects, the standard dose of 10 mL CPCGI had the best effect on reducing the degree of disability and improving abilities of daily living.

Parkinson’s disease (PD) is a common neurodegenerative disorder of middle-aged and elderly people, clinically characterized by resting tremor, myotonia, reduced movement, and impaired postural balance. Clinically, patients with PD are often administered levodopa (L-DOPA) to improve their symptoms. However, after years of L-DOPA treatment, most patients experience complications of varying severity, including the “on-off phenomenon”, decreased efficacy, and levodopa-induced dyskinesia (LID). The development of LID can seriously affect the quality of life of patients, but its pathogenesis is unclear and effective treatments are lacking. Glutamic acid (Glu)-mediated changes in synaptic plasticity play a major role in LID. The N-methyl-D-aspartic acid receptor (NMDAR), an ionotropic glutamate receptor, is closely associated with synaptic plasticity, and neuroinflammation can modulate NMDAR activation or expression; in addition, neuroinflammation may be involved in the development of LID. However, it is not clear whether NMDA receptors are co-regulated with neuroinflammation during LID formation. Here we review how neuroinflammation mediates the development of LID through the regulation of NMDA receptors, and assess whether common anti-inflammatory drugs and NMDA receptor antagonists may be able to mitigate the development of LID through the regulation of central neuroinflammation, thereby providing a new theoretical basis for finding new therapeutic targets for LID.

Autoimmune encephalitis (AE) is an autoimmune disease in the central nervous system. Clinical manifestations include cognitive dysfunction, psychiatric-behavioral abnormalities, epilepsy, motor disorders, speech disorders, and memory impairment. Some patients do not have the characteristic clinical manifestations of the disease when they see a doctor, so they are easily diagnosed incorrectly. Autoimmune antibodies originate from genetic and acquired factors. Clinical data have found a correlation between ovarian teratoma and autoimmune encephalitis. This case reports a 34-year-old woman who was diagnosed with teratoma-associated anti-N-methyl-D- aspartate receptor-mediated autoimmune encephalitis called anti-N-methyl-D-aspartate receptor encephalitis with bilateral hearing loss in 2021. Through this case report, clinicians will pay attention to autoimmune encephalitis and raise awareness of the specific clinical manifestations of autoimmune encephalitis, and focus on early identification. It means that clinicians should be familiar with the representative clinical manifestations of the disease.

Background This study was aimed to investigate whether patients with epilepsy (PWE) have higher depression and anxiety levels than the normal population in low-risk areas for coronavirus disease 2019 (COVID-19) in the northern part of Guizhou Province, China, during the COVID-19 epidemic, to evaluate their knowledge on COVID-19, and to analyze related factors for the psychological distress of PWE at this special time. Methods The survey was conducted online from February 28, 2020 to March 7, 2020 via a questionnaire. PWE from the outpatient clinic of epilepsy of the Affiliated Hospital of Zunyi Medical University, and healthy people matched for age and sex, participated in this study. Mental health was assessed via a generalized anxiety self-rating scale (GAD-7) and the self-rating depression scale (PHQ-9). The knowledge of COVID-19 in both groups was investigated. Results There were no significant differences in the general demographics between the PWE and healthy control groups. The scores of PHQ-9 ( P < 0.01) and GAD-7 ( P < 0.001) were higher in the PWE group than in the healthy group. There was a significant difference in the proportions of respondents with different severities of depression and anxiety, between the two groups, which revealed significantly higher degree of depression and anxiety in PWE than in healthy people ( P = 0, P = 0). Overwhelming awareness and stressful concerns for the pandemic and female patients with epilepsy were key factors that affect the level of anxiety and depression in PWE. Further, the PWE had less accurate knowledge of COVID-19 than healthy people ( P < 0.001). There was no statistically significant difference between the two groups in the knowledge of virus transmission route, incubation period, susceptible population, transmission speed, clinical characteristics, and isolation measures on COVID-19 ( P > 0.05). PWE knew less about some of the prevention and control measures of COVID-19 than healthy people. Conclusions During the COVID-19 epidemic, excessive attention to the epidemic and the female sex are factors associated with anxiety and depression in PWE, even in low-risk areas.

Abstract Encephalitis is one of the common diseases in neurology. Early diagnosis and appropriate treatments are essential. Autoimmune encephalitis (AE) generally refers to a type of encephalitis mediated by autoimmune mechanisms. It is gradually considered to be an important cause of reversible encephalitis caused by noninfectious factors. It can occur in children, adolescents, and adults, and is clinically characterized by multifocal or diffuse brain damage such as personality changes, seizures, and cognitive impairment, with an overall good effect of immunotherapy. According to the clinical features of the patients, blood and cerebrospinal fluid tests, neuroelectrophysiology, cranial imaging, treatment and prognosis, AEs can be broadly divided into specific antigen (antibody)‐related AEs and nonspecific antigen (or antibody) ‐related AEs. With the development of AEs research, more and more anti‐neuron antibodies have been found, which provides an important reference for the diagnosis and treatment of AEs. Understanding the knowledge about AEs is important to discover new diseases and deepen the understanding of the immunopathological mechanisms of existing central nervous system diseases. Anti‐γ‐aminobutyric acid B (GABA‐B) receptor encephalitis is a type of AE, but this disease is rare in AE, often develop to the clinical manifestations of marginal encephalitis, accompanied by obvious seizures or status epilepticus, Some patients had tumors, mainly small‐cell carcinoma, prompt diagnosis, early immunotherapy and, if necessary, tumor treatment resulted in complete or partial neurological improvement in most patients.

Introduction: The purpose of this paper is to evaluate the efficacy and safety of acupuncture in the treatment of childhood attention deficit hyperactivity disorder (ADHD). Methods and analysis: We will electronically search PubMed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to acupuncture treating pediatric ADHD will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The scores of Revised Conners' Parent Rating Scale (CPRS-R), Conners Teacher Rating Scale (CTRS-R), and Child Behavior Checklist (CBCL) will be the primary outcomes. Besides, the scores of the Conners Continuous Performance Test, Internal Restlessness Scale, and Behavior Assessment System for Children (BASC), and the possible adverse events will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), while dichotomous data will be expressed in the form of relative risk with 95% CIs. Ethics and dissemination: The protocol of this systematic review (SR) does not require ethical approval because it does not involve humans. We will publish this article in peer-reviewed journals and presented at relevant conferences. Systematic review registration: OSF Registries, DOI: 10.17605/OSF.IO/XVYP9 (https://osf.io/xvyp9)

Epilepsy is a chronic nervous system disease. Excessive increase of the excitatory neurotransmitter glutamate in the body results in an imbalance of neurotransmitters and excessive excitation of neurons, leading to epileptic seizures. Long-term recurrent seizures lead to behavior and cognitive changes, and even increase the risk of death by 2- to 3-fold relative to the general population. Adenosine A1 receptor (A1R), a member of the adenosine system, has notable anticonvulsant effects, and adenosine levels are controlled by the type 1 equilibrative nucleoside transporter (ENT1); in addition the p38 MAPK signaling pathway is involved in the regulation of ENT1, although the effect of its inhibitors on the expression levels of A1R and ENT1 is unclear. Therefore, in the present study, SB203580 was used to inhibit the p38 MAPK signaling pathway in rats, and the expression levels of A1R and ENT1 in the brain tissue of rats with acute LiCl-pilocarpine-induced status epilepticus was detected. SB203580 decreased pathological damage of hippocampal neurons, prolonged seizure latency, reduced the frequency of seizures, and decreased levels of A1R and ENT1 protein in rats.

Background and purpose: The present study was designed to investigate the potential role and the mechanism of equilibrative nucleoside transporter 1 (ENT1) on neuronal apoptosis and neurological deficits after middle cerebral artery occlusion (MCAO) in rats. Methods: One hundred and thirty-four male Sprague-Dawley rats were subjected to two hours of MCAO followed by reperfusion. The time course of the expression level of ENT1 and phosphorylation of CREB were detected by western blot and immunofluorescence staining. Another set of animals were administrated with NBTI, the ENT1 inhibitor, by daily intraperitoneal injection starting at 0.5 h post-MCAO, infarction volume and neurological deficits were measured both at 24 h and 72 h post MCAO. We further explored the neuroprotection machenism by using H89, cAMP dependent protein kinase inhibitor, the expression of Bcl-2, Bax, phosphorylated CREB and Cleaved caspase-3 were quantified by Western blot, neuronal apoptosis were analyed by TUNEL staining. Results: The endogenous expression of ENT1 were significantly increased and peaked at 12 h after MCAO. High-dose of NBTI (15 mg/kg) reduced brain infarction volume and improved neurologic deficits both at 24 h and 72 h post MCAO. Moreover, NBTI significantly increased the level of CREB phosphorylation and extracellular adenosine concentration, and decreased the neuronal apoptosis 24 h after MCAO. NBTI treatment reduced the expression of Bax and cleaved caspase-3, while up-regulated Bcl-2 compared with vehicle group. These effects were abolished by H89 pretreatment. Conclusions: ENT1 inhibition prevented neuronal apoptosis and improves neurological deficits through cAMP/ PKA/CREB/Bcl-2 signaling pathway after MCAO in rats. ENT1 might be an effective target in the treatment strategy for ischemic stroke.

BACKGROUND AND PURPOSE:The present study was designed to investigate the potential role and the mechanism of equilibrative nucleoside transporter 1 (ENT1) on neuronal apoptosis and neurological deficits after middle cerebral artery occlusion (MCAO) in rats. METHODS:One hundred and thirty-four male Sprague-Dawley rats were subjected to two hours of MCAO followed by reperfusion. The time course of the expression level of ENT1 and phosphorylation of CREB were detected by western blot and immunofluorescence staining. Another set of animals were administrated with NBTI, the ENT1 inhibitor, by daily intraperitoneal injection starting at 0.5 h post-MCAO, infarction volume and neurological deficits were measured both at 24 h and 72 h post MCAO. We further explored the neuroprotection machenism by using H89, cAMP dependent protein kinase inhibitor, the expression of Bcl-2, Bax, phosphorylated CREB and Cleaved caspase-3 were quantified by Western blot, neuronal apoptosis were analyed by TUNEL staining. RESULTS:The endogenous expression of ENT1 were significantly increased and peaked at 12 h after MCAO. High-dose of NBTI (15 mg/kg) reduced brain infarction volume and improved neurologic deficits both at 24 h and 72 h post MCAO. Moreover, NBTI significantly increased the level of CREB phosphorylation and extracellular adenosine concentration, and decreased the neuronal apoptosis 24 h after MCAO. NBTI treatment reduced the expression of Bax and cleaved caspase-3, while up-regulated Bcl-2 compared with vehicle group. These effects were abolished by H89 pretreatment. CONCLUSIONS:ENT1 inhibition prevented neuronal apoptosis and improves neurological deficits through cAMP/PKA/CREB/Bcl-2 signaling pathway after MCAO in rats. ENT1 might be an effective target in the treatment strategy for ischemic stroke.