Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling.

Diterpene ginkgolides meglumine injection (DGMI) is a therapeutic extract of Ginkgo biloba L, which has been used for the treatment of cerebral ischemic stroke in China. Ginkgolides A, B and C are the main components of DGMI. This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion. Administration of DGMI significantly decreased rat neurological deficit scores, reduced brain infarct volume, and induced protein kinase B (Akt) phosphorylation, which prompted the nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and phosphorylation of the survival regulatory protein cyclic AMP-responsive element binding protein (CREB). Nrf2 activation led to expression of the downstream protein heme oxygenase-1 (HO-1). In addition, PC12 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) in vitro, treatment with DGMI (1, 10 and 20 µg/mL) or ginkgolides A, B or C (10 µmol/L for each) significantly reduced PC12 cell death and increased phosphorylation of Akt, nuclear translocation of Nrf2 and activation of CREB. Activation of Nrf2 and CREB could be reversed by co-treatment with a phosphoinositide-3-kinase (PI3K) inhibitor LY294002. These observations suggest that ginkgolides act as novel extrinsic regulators activating both Akt/Nrf2 and Akt/CREB signaling pathways, protecting against cerebral ischemia/reperfusion (I/R) damage in vivo and in vitro.

[Salvianolic acid A alleviate the brain damage in rats after cerebral ischemia-reperfusion through Nrf2/HO-1 pathway].

The aim of present study is to investigate the protective effects and mechanism of salvianolic acid A (SAA) on cerebral ischemia-reperfusion injury in rats. The model was established with middle cerebral artery occlusion and reperfusion (MCAO/R) with ischemia for 1.5 h and reperfusion for 24 h in adult male SD rats. After the behavior assessment, TTC assay was used to calculate the infarct volume of rat brain; the distribution of Nrf2 in nuclear and cytoplasm and expression of HO-1 were detected by Western blot. The PC12 cells injury model was established with oxygen-glucose deprivation for 6 h and reintroduction for 24 h. Cell viability was determined with MTT assay, and the expression of Nrf2 and HO-1 were detected through immunofluorescence staining. The mechanisms were investigated in PC12 cells with Nrf2 knocking down by siRNA. SAA (10 and 20 mg·kg(-1)) significantly reduced the neuronal damage in MCAO/R model, and SAA(0.5 and 5 µmol·L(-1)) increased cell viability in PC12 cells injury model. Meanwhile, the nuclear translocation of Nrf-2 and the expression of HO-1 were increased in PC12 cell and rats brain. SAA exhibited anti-cerebral ischemia- reperfusion effects. The mechanism may be related to activation of Nrf2/HO-1 signaling pathway, which promotes the synthesis and nuclear translocation of Nrf2 to enhance the expression of the antioxidant protein HO-1.

Efficacy and safety of acupuncture for polycystic ovary syndrome: An overview of systematic reviews.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility, bringing serious harm to women's physical and mental health. Acupuncture may be an effective treatment for PCOS. However, systematic reviews (SRs) on the efficacy and safety of acupuncture for PCOS have reported inconsistent results, and the quality of these studies has not been adequately assessed. OBJECTIVE: To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS, as well as to assess the quality and risks of bias of the available SRs. SEARCH STRATEGY: Nine electronic databases (Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Chinese Science and Technology Periodical Database, and China Biology Medicine disc) were searched from their establishment to July 27, 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "acupuncture," "polycystic ovary syndrome," and "systematic review." INCLUSION CRITERIA: SRs of randomized controlled trials that explored the efficacy and (or) safety of acupuncture for treating patients with PCOS were included. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted study data according to a predesigned form. Tools for evaluating the methodological quality, risk of bias, reporting quality, and confidence in study outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), were used to score the included SRs. RESULTS: A total of 885 studies were retrieved, and 11 eligible SRs were finally included in this review. The methodological quality of 2 SRs (18.18%) was low, while the other 9 SRs (81.82%) were scored as extremely low. Four SRs (36.36%) were considered to be of low risk of bias. As for reporting quality, the reporting completeness of 9 SRs (81.82%) was more than 70%. Concerning the confidence in study results, 2 study results were considered to have a high quality of evidence (3.13%), 14 (21.88%) a "moderate" quality, 28 (43.75%) a "low" quality, and 20 (31.24%) considered a "very low" quality. Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate (CPR) and ovulation rate, and reduce luteinizing hormone/follicle-stimulating hormone ratio, homeostasis model assessment of insulin resistance, and body mass index (BMI). When compared with medicine alone, acupuncture alone also can improve CPR. Further, when compared with no intervention, acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI. Acupuncture was reported to cause no adverse events or some adverse events without serious harm. CONCLUSION: The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence. More high-quality studies are needed to support the use of acupuncture in PCOS.

[Trans-sylvian-insular approach endoscopic surgery for basal ganglia hypertensive hemorrhage].

OBJECTIVE: To explore the operative techniques and efficacy of trans-sylvian-insular approach endoscopic surgery for hypertensive basal ganglia hemorrhage. METHODS: A retrospective analysis was conducted in 54 patients with hypertensive basal ganglia hemorrhage from December 2009 to December 2011. All of them underwent neuroendoscopic surgery via a trans-sylvian-insular approach. The hematoma volume was 30 - 40 ml (n = 8), 40 - 50 ml (n = 42) and > 50 ml (n = 4). And the Glasgow Coma Scale (GCS) was 8 - 12 (n = 48) and 13 - 15 (n = 6). RESULTS: The clearance rate of hematoma was > 90% (n = 44) and 80% - 90% (n = 10). None suffered re-hemorrhage or death. CONCLUSION: As a mini-invasive and efficacious approach for hypertensive basal ganglia hemorrhage, trans-sylvian-insular approach endoscopic surgery has a high clearance rate of hematoma is high and causes minimal damage to normal brain tissue. It is worth of clinical promotion.

The role of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type receptor modulators in object recognition memory reconsolidation.

OBJECTIVE: Numerous studies suggest that the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type (AMPA) receptor appears to play a central role in mediating brain functions, such as learning and memory. Trafficking of this receptor is related to different long-term memory processes. This study explores the role of two AMPA receptor (AMPAR) modulators in object recognition memory (ORM) reconsolidation. METHODS: First, the effects of immediate administration of each drug after memory reactivation were investigated and compared. Then, this drug's efficient time window and its effects without memory reactivation were investigated. RESULTS: Immediate CX546 administration after reactivation did not affect ORM reconsolidation. In contrast, administration of 10-mg/kg NBQX significantly impaired ORM reconsolidation within a 6-h time window. Importantly, the observed effects were not attributed to the exploratory behavior or locomotor activity of mice. CONCLUSION: These findings provide new evidence that the AMPA receptor plays an important role in the reconsolidation phase of ORM.

P-Coumaric Acid Reverses Depression-Like Behavior and Memory Deficit Via Inhibiting AGE-RAGE-Mediated Neuroinflammation.

Depression, a mood disorder, affects one in fifteen adults, has multiple risk factors and is associated with complicated underlying pathological mechanisms. P-coumaric acid (p-CA), a phenolic acid, is widely distributed in vegetables, fruits and mushrooms. P-CA has demonstrated a protective role against oxidative stress and inflammation in various diseases, including cardiovascular disease, diabetes and cancer. In the current study, we investigated the protection of p-CA against depression and memory impairment in a corticosterone (CORT)-induced chronic depressive mouse model. CORT administration resulted in depression-like behaviors and memory impairment. P-CA treatment alleviated CORT-induced depression-related behaviors and memory impairment. Network pharmacology predicted that p-CA had multiple targets and mediated various signaling pathways, of which inflammation-associated targets and signaling pathways are predominant. Western blotting showed CORT-induced activation of the advanced glycation end product (AGE)-receptor of AGE (RAGE) (AGE-RAGE) signaling and increased expression of the proinflammatory cytokines interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNFα) in the hippocampus, while p-CA treatment inactivated AGE-RAGE signaling and decreased the levels of IL-1ß and TNFα, suggesting that protection against depression and memory impairment by p-CA is mediated by the inhibition of inflammation, mainly via the AGE-RAGE signaling pathway. Our data suggest that p-CA treatment will benefit patients with depression.

Effect of non-pharmacological interventions for overweight/obese women with polycystic ovary syndrome on ovulation and pregnancy outcomes: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Most overweight/obese women with polycystic ovary syndrome (PCOS) have infertility issues which are difficult to treat. Non-pharmacological interventions used for the management of infertility include lifestyle interventions, acupuncture therapies and nutritional supplements. These interventions have been reported to be beneficial in alleviating infertility among overweight women with PCOS. However, effect and safety of these non-pharmacological interventions vary, and there is no standard method of clinical application. Therefore, it is necessary to conduct a systematic review and network meta-analysis (NMA) to rank these non-pharmacological interventions in terms of effect and determine which one is more effective for clinical application. METHODS AND ANALYSIS: We will retrieve eight databases including Cochrane Library, Medline, Embase, PsycINFO, Chinese National Knowledge Infrastructure, WanFang Data, the Chongqing VIP Database and China Biology Medicine disc from their inceptions onwards. In addition, four clinical trial registries and the related references will be manually retrieved. The primary outcome will be clinical pregnancy. Live birth, ovulation, pregnancy loss, multiple pregnancy and adverse events related to interventions will be considered as the secondary outcomes. STATA software V.15.0 and Aggregate Data Drug Information System V.1.16.8 will be used to conduct pairwise meta-analysis and NMA. The Grading of Recommendations Assessment, Development and Evaluation system will be adopted to evaluate the certainty of evidence. ETHICS AND DISSEMINATION: Ethical approval will not be required because the study will not include the original information of participants. The results will be published in a peer-reviewed journal or disseminated in relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021283110.

Trans-urocanic acid facilitates spatial memory, implications for Alzheimer's disease.

Trans-urocanic acid (trans-UCA) is an isomer of cis-UCA and is widely distributed in the brain, predominantly in the hippocampus and prefrontal cortex. Previous studies have investigated the role of trans-UCA in non-spatial memory; however, its influence on spatial memory remains unclear. In the present study, network pharmacology strategy and behavioral testing were used to evaluate the role of trans-UCA in spatial memory and predict its possible mechanism. The results showed that there are 40 intersecting targets between trans-UCA and spatial memory identified by several databases and Venn diagram, indicating that trans-UCA may be involved in spatial memory. Behavioral results show that trans-UCA facilitates spatial working memory in the Y-maze test as well as spatial recognition memory acquisition, consolidation and retrieval in an object location recognition (OLR) task. Furthermore, PPI (protein-protein interaction) network analysis, GO (gene ontology) and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses show that the molecular mechanisms underlying the enhancing effect of trans-UCA on spatial memory are mainly associated with the regulation of insulin, mitogen-activated protein kinase (MAPK) and nuclear factor Kappa B (NF-κB) signaling pathways, serotonergic synapse and arginine and proline metabolism. The results of this study suggest that trans-UCA facilitates spatial memory in the Y-maze test and OLR task and may offer therapeutic potential for Alzheimer's disease (AD). The underlying mechanisms predicted by network pharmacology should be further verified.

Transcutaneous electrical acupoint stimulation for pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A systematic review and meta-analysis.

Background: Infertility is a common health problem affecting couples of childbearing age. The proposal of in vitro fertilization-embryo transfer (IVF-ET) solves the problem of infertility to a certain extent. However, the average success rate of IVF-ET is still low. Some studies conclude that transcutaneous electrical acupoint stimulation (TEAS) could improve pregnancy outcomes in women undergoing IVF-ET, however, there is a lack of comprehensive synthesis and evaluation of existing evidence. Objective: To conduct a systematic review and meta-analysis to assess whether TEAS is effective and safe to improve the pregnancy outcomes for women undergoing IVF-ET. Methods: Eight online databases were searched from inception to 19 November 2021. In addition, four clinical trial registries were also searched, relevant references were screened, and experts were consulted for possible eligible studies. Randomized controlled trials (RCTs) that included patients with infertility who underwent IVF and used TEAS as the main adjuvant treatment vs. non-TEAS or mock intervention controls were included. The clinical pregnancy rate (CPR) was considered the primary outcome. High-quality embryo rate (HQER), live birth rate (LBR), biochemical pregnancy rate (BPR), ongoing pregnancy rate (OPR), early miscarriage rate (EMR), birth defects rate (BDR), and adverse events related to interventions were regarded as secondary outcomes. The selection, data extraction, risk of bias assessment, and data synthesis were conducted by two independent researchers using Endnote software V.9.1 and Stata 16.0 software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the evidence quality of each outcome. Results: There were 19 RCTs involving 5,330 participants included. The results of meta-analyses showed that TEAS can improve CPR [RR = 1.42, 95% CI (1.31, 1.54)], HQER [RR = 1.09, 95% CI (1.05, 1.14)], and BPR [RR = 1.45, 95% CI (1.22, 1.71)] of women underwent IVF-ET with low quality of evidence, and improve LBR [RR = 1.42, 95% CI (1.19, 1.69)] with moderate quality of evidence. There was no significant difference in EMR [RR = 1.08, 95% CI (0.80, 1.45)] and BDR [RR = 0.93, 95% CI (0.13, 6.54)] with very low and moderate quality of evidence, respectively. A cumulative meta-analysis showed that the effective value of TEAS vs. controls was relatively stable in 2018 [RR = 1.52, 95% CI (1.35, 1.71)]. In addition, no serious adverse events associated with TEAS were reported. Conclusion: Our findings suggest that TEAS may be an effective and safe adjuvant treatment for women undergoing IVF-ET to improve pregnancy outcomes. However, the current evidence quality is considered to be limited, and more high-quality RCTs are needed for further verification in the future. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021238871, identifier: CRD42021238871.

Viciamingyueshanensis (Fabeae, Papilionoideae, Fabaceae), a new species from western Jiangxi, China.

Viciamingyueshanensis, a new species from the Mingyue Mountain Region of western Jiangxi, China, is described and illustrated. It is a perennial climbing liana that always links to riparian woods. A morphological comparison indicated that the new species is closely similar to Viciataipaica K. T. Fu and Viciadichroantha Diels; however, it differs from the other two species by several salient characters, such as plant indumentum, stipule shape, corolla colour, bractlet shape and calyx shape. Photographs, a preliminary conservation assessment, table of morphological characters and distribution map comparing this new species to two morphologically-similar species are also provided.

Systematic Review and Meta-Analysis of Acupuncture for Pain Management in Women Undergoing Transvaginal Oocyte Retrieval.

OBJECTIVE: To obtain evidence-based conclusions about the effect of acupuncture on pain relief in women undergoing oocyte retrieval, the results of randomized controlled trials (RCTs) that met the criteria were assessed on the Pain Assessment Scale and pregnancy indicators. SEARCH METHODS: References were retrieved in MEDLINE, EMBASE, CNKI database, CBM database, VIP database, and Wanfang database from inception to June 26, 2021. Unpublished ongoing trials were searched in the Clinical Trials Registries. This review included RCTs that investigated the acupuncture analgesic effects during oocyte retrieval in women undergoing in vitro fertilization. RESULTS: Fourteen RCTs (2503 women in total) with six types of comparisons were finally included. The quality of concluding evidence was generally low or very low. Performance bias and outcome assessment bias was the main risk of bias of the included studies. Acupuncture combined with conscious sedation and analgesia (CSA) was associated with less intraoperative (SMD=-1.03; 95% CI: -1.71 to -0.36) and postoperative (SMD = -1.11; 95% CI: -1.51 to -0.71) pain compared to receive CSA alone in oocyte retrieval. Acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) was more effective than using NSAIDs alone for postoperative analgesia (MD = -1.76; 95% CI: -2.08 to -1.44). CONCLUSION: Acupuncture complex analgesic therapy is more effective than utilizing CSA or NSAIDs alone. Furthermore, there is no significant consensus on whether there is an analgesic effect of applying acupuncture alone during oocyte retrievals, which needs further research. The overall results should be interpreted with caution due to the high risk of bias/low-GRADE scores among these studies. PROTOCOL AND REGISTRATION: PROSPERO registration number: CRD42020170095.

Prenylated benzophenone peroxide derivatives from Hypericum sampsonii.

Two new prenylated benzophenone peroxide derivatives, peroxysampsones A and B (1 and 2, resp.), together with a known compound, plukenetione C (3), were isolated from the roots of the Chinese medicinal plant Hypericum sampsonii, and their structures were elucidated by detailed spectral analysis. These compounds are the unusual peroxides of polyprenylated benzophenone derivatives, containing the unique caged moiety of 4,5-dioxatetracyclo[9.3.1.1(9,13).0(1,7)]hexadecane-12,14,15-trione. In the biological test, peroxysampsone A (1) showed comparable activity with norfloxacin against a NorA over-expressing multidrug-resistant (MDR) strain of Staphylococcus aureus SA-1199B.

[Operative approach for hydrocephalus associated with cerebellar tonsillar hernia].

OBJECTIVE: To assess the pre-operative examination and operative approach for hydrocephalus associated with cerebellar tonsillar hernia. METHODS: A retrospective analysis was conducted for 24 patients of hydrocephalus associated with cerebellar tonsillar hernia. All subjects received both pre-operative and post-operative Cine MRI examinations to detect the velocity and quantity of cerebrospinal fluid (CSF) at the important sites in ventricular system. A majority of cases had endoscopic third ventriculostomy (ETV) while others underwent both ETV and endoscopic posterior cranial fossa decompression. RESULTS: The pre-operative CSF hydrodynamics of all cases were abnormal at foramen magnum. A post-operative CSF flow through stoma might be detected by Cine MRI in all cases. The clinical symptoms improved to different extents in 21 cases while another two cases showed no improvement. Later these two patients underwent endoscopic posterior cranial fossa decompression. Cerebellar tonsillar hernia improved in 14 cases. CONCLUSION: Cine MRI can detect the CSF hydrodynamics at craniocervical junction so as to help a surgeon determine the time and the plan of operation. Most cases of hydrocephalus associated with cerebral tonsillar hernia are of obstructive hydrocephalus. The efficacy of ETV for hydrocephalus has been confirmed. Also ETV has a therapeutic effect for cerebellar tonsillar hernia and syringomyelia.

Angiopoietin-1 accelerates Alzheimer's disease via FOXA2/PEN2/APP pathway in APP/PS1 mice.

Angiopoietin-1 (Ang-1), a regulatory angiogenesis protein and it has been found to be involved in the occurrence and progression of Alzheimer's disease. However, it was still to be addressed the distinctly role and the molecular mechanisms of Ang-1 affects Alzheimer's disease. Our data suggest that Ang-1 aggravated the accumulation of Aß42 and cognitive decline in APP/PS1 mice. The upregulation of APPß is essential for Aß42 production in N2a cells overexpressing the mutational human APP gene (N2a/APP695 cells), while downregulation of PEN2 could reduce APP expression. Silencing of FOXA2 lead to inhibition of APP expression, as well as decrease of Aß42 contents. In conclusion, Ang-1 has an accelerative effect on Alzheimer's disease by increasing the secretion of Aß42 via FOXA2/PEN2/APP pathway.

Antiplasmodial isoflavanones from the roots of Sophora mollis.

Six new prenylated isoflavanones named sophoronols A-F (1-6), together with eight phenolic constituents, were isolated from the roots of Sophora mollis. Their structures and stereochemistry were established by 1D and 2D NMR techniques, especially HMBC and NOESY as well as CD results. Componds 3 and 5 exhibited moderate anitplasmodial activity against the CQS D10 strain of Plasmodium falciparum, with IC(50) values of 12.9 and 12.8 microM, respectively.

[Endoscopic therapy for obstructive hydrocephalus caused by cysts in the pathway of CSF circulation].

OBJECTIVE: To explore the process and technique of neuroendoscopic operation to treat obstructive hydrocephalus caused by cysts located in the pathway of CSF circulation. METHODS: The cine MRI examinations and endoscopic operations were taken to treat 30 cases with obstructive hydrocephalus. Among all the cases, there are 11 intraventricular cysts (8 lateral ventricular cysts, 4 fourth ventricular cysts), 4 suprasellar arachnoid cysts, 1 quadrigeminal cistern arachnoid cyst, 6 Dandy-Walker malformations and 8 posterior fossa arachnoid cysts. RESULTS: CSF dynamic of all patients improved to different extents post-operation. It was observed that CSF passed through the stoma after ETV in all patients. The volume of 9 intraventricular cysts, 4 suprasellar arachnoid cysts, 1 quadrigeminal cistern arachnoid cyst and 4 posterior fossa arachnoid cysts diminished for different degrees. There were no surgery-related serious complications or deaths. There were not cyst enlarged and stoma obstructed cases. CONCLUSIONS: Obstructive hydrocephalus caused by cysts in the pathway of CSF circulation is the optimal indication for neuro-endoscopic surgery. After resecting cyst partially, we should take the endoscopic third ventriculostomy to rebuild the passway of CSF and elevate the cranial compliance. Cine MRI and radionuclide cisternography are helpful to understand the CSF dynamic and absorption.

[Dihydromyricetin ameliorates chronic social defeat stress induced cognitive and affective disorder in mice].

OBJECTIVE: To investigated the effects of dihydromyricetin on cognitive and affective disorders induced by chronic social defeat stress and its possible mechanism in mice. METHODS: C57BL/6J mice were randomly divided into control group (Control), chronic social defeat stress group (CSDS) and chronic social defeat stress + DHM group (CSDS+DHM) (14 mice in each group). The mice received chronic social defeat stress and were injected with DHM or vehicle intraperitoneally. A part of mice were subjected to (10 mice of each group) novel object recognition test (NOR), Y maze test, open field test (OFT), social interaction test (SIT), forced swimming test (FST) and tail suspension test (TST). The other mice (4 mice of each group) were decapitated and the expression levels of SIRT1 in hippocampus were detected by Western blot. RESULTS: Compared with the control group, the learning and memory of the CSDS group were reduced significantly, the anxiety level was increased significantly, the immobility time in TST and FST was increased significantly, and the SIRT1 protein level in hippocampus was reduced significantly (P＜ 0.05 or P＜ 0.01); Compared with the CSDS group, the learning and memory of the CSDS + DHM group were improved significantly, the anxiety level of the mice was reduced significantly, and the immobility time in TST and FST was reduced significantly. The protein level of SIRT1 in hippocampus was increased significantly (P＜ 0.05 or P＜ 0.01). CONCLUSION: DHM ameliorates the cognitive impairment, anxiety like behavior and depression like behavior of mice induced by CSDS and up-regulates the expression of SIRT1 protein.

Glutamate transporter GLT1 inhibitor dihydrokainic acid impairs novel object recognition memory performance in mice.

Glutamate transporter GLT1 mediates glutamate uptake, and maintains glutamate homeostasis in the synaptic cleft. Previous studies suggest that blockade of glutamate uptake affects synaptic transmission and plasticity. However, the effect of GLT1 blockade on learning and memory still receives little attention. In the present study, we examined the effect of unilateral intracerebroventricular injection of dihydrokainic acid (DHK), a GLT-1 inhibitor, on novel object recognition (NOR) memory performance. The NOR task involved three sessions including habituation, sampling and test. In experiment 1, DHK injection 0.5 h pre-sampling impaired short-term NOR memory performance. In experiment 2, DHK injection 0.5 h pre-sampling impaired long-term NOR memory acquisition. In experiment 3, DHK injection immediately but not 6 h post-sampling impaired long-term NOR memory consolidation. In experiment 4, DHK injection 0.5 h pre-test impaired long-term NOR memory retrieval. Furthermore, DHK-induced memory performance impairment was not due to its effects on nonspecific responses such as locomotor activity and exploratory behavior. The current findings further extend previous studies on the effects of disruption of glutamate homeostasis on learning and memory.

Application of neuroendoscopic surgical techniques in the assessment and treatment of cerebral ventricular infection.

Cerebral ventricular infection (CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques (NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery (NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I (n = 3), Grade II (n = 13), Grade III (n = 10), and Grade IV (n = 6) CVI. The three patients with grade I CVI underwent one NES, the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two (n = 3) or three (n = 3) NESs. The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures. Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus, 18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6- to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China.

Apelin-13 Upregulates BDNF Against Chronic Stress-induced Depression-like Phenotypes by Ameliorating HPA Axis and Hippocampal Glucocorticoid Receptor Dysfunctions.

Localization of apelin and its receptor APJ in limbic structures such as the hippocampus suggests potential involvement of apelin/APJ signaling in stress-related emotional responses. We have recently reported that apelin-13 exerts antidepressant-like actions in acute stressed rats, and that the hippocampus is a critical brain region mediating its actions. However, the neural mechanism underling antidepressant-like actions of apelin-13 is still largely unknown. The aim of the present study is to determine whether apelin-13 ameliorates chronic water-immersion restraint stress (CWIRS)-induced depression-like phenotypes and its neural mechanism in rats. Here, we report that CWIRS exposure leaded to upregulation of apelin/APJ signaling in the hippocampus. Apelin-13 ameliorated CWIRS-induced depression-like phenotypes including hedonic-like deficit and behavioral despairs. Moreover, apelin-13 ameliorated hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and hippocampal BDNF expression deficit and glucocorticoid receptor (GR) nucleus translocation hypoactivity in chronic stressed rats. Finally, apelin-13-mediated effects were blocked by the selective TrkB receptor antagonist ANA-12. These results suggest that apelin-13 upregulates BDNF against chronic stress-induced depression-like phenotypes by ameliorating HPA axis and hippocampal GR dysfunctions.