The mitochondria-targeted small molecule SS31 delays progression of behavioral deficits by attenuating ß-amyloid plaque formation and mitochondrial/synaptic deterioration in APP/PS1 mice.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and ß-amyloid (Aß) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Aß40/Aß42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Aß levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD.

Chinese version of the auditory verbal learning test: normative study and clinical applications in Chinese-speaking population in Shijiazhuang city.

OBJECTIVE: The purposes were to establish standardized values for the Auditory Verbal Learning Test (AVLT) in the communities of Shijiazhuang city (China), with particular focus on the influences of age, education and sex, and to detect the discriminant validity data of the AVLT in patients with acute ischemic stroke (AIS). METHODS: 406 Chinese-speaking subjects (age: 50-84 years old) from Shijiazhuang city, were brought into this study. Using linear regression analyses, standardized values were developed for three variables of interest, including scores on short-term memory (sum of AVLT trials 1-3), delayed recall (AVLT trial 4), and an index representing recognition memory corrected for false-positive identifications (AVLT trial 5). 177 patients with AIS were included to probe the discriminant validity of the AVLT. RESULTS: The linear regression analysis showed statistically significant effect of age and sex on all trials of the AVLT. Years of education contributed significantly to trial 1-3 and trial 4 but not trial 5. Based on the results obtained, trail 1-3 and trail 4 of AVLT norms were stratified by age (3 strata), education (2 strata), and sex (2 strata). Trail 5 norms were stratified by age (3 strata) and sex (2 strata). Moreover, AIS groups performed significantly worse on most AVLT trials than matched cognitively healthy controls. CONCLUSIONS: Normative data stratified by age, education and sex for the Chinese-speaking community-residents in Shijiazhuang was presented for use in research and clinical settings. The AVLT measures adequately differentiated between the cognitive performance (especially memory decline) of healthy adults and patients with AIS.

Efficacy of escitalopram for poststroke depression: a systematic review and meta-analysis.

Depression is very common after stroke, causing multiple sequelae. We aimed to explore the efficacy of escitalopram for poststroke depression (PSD). PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, Clinical trials. gov, Wan fang Data (Chinese), VIP (Chinese) and CNKI (Chinese) were retrieved from inception to May 2021. We recruited Randomized Controlled Trials (RCTs) which met the inclusion criteria in our study. The depression rating scores, the incidence of PSD, adverse events as well as functional outcomes were analyzed. 11 studies and 1374 participants were recruited in our work. The results were depicted: the reduction of depression rating scores was significant in the escitalopram groups and the standard mean difference (SMD) was - 1.25 (P < 0.001), 95% confidence interval (95% CI), - 1.82 to - 0.68; the risk ratio (RR) of the incidence of PSD was 0.52 (95% CI, 0.29 to 0.91; P = 0.007 < 0.05), which was significantly lower in the escitalopram groups; Escitalopram is safe for stroke patients; there was improvement of the motor function. However, in sensitivity analyses, the conclusions of the motor function and the incidence of drowsiness were altered. The study suggests that escitalopram has a potentially effective role compared with control groups and demonstrates escitalopram is safe. However, the results of the motor function and the incidence of drowsiness should be considered carefully and remain to be discussed in the future.

A case report of posterior reversible encephalopathy syndrome caused by ANCA-associated vasculitis case report and retrospective analysis.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a reversible syndrome clinically manifested by significant variations in neuroimaging. Early treatment is indispensable to achieve the reversibility, which requires the punctual alleviation of its inducing factors. PATIENT CONCERNS: Most symptoms of posterior reversible encephalopathy syndrome (PRES) patients can be dispelled followed by a good prognosis after the inducement removal. The patient died due to the untimely diagnosis and treatment of the primary disease. Therefore, sufficient attention should be paid to the PRES induced by ANCA-associated vasculitis (AAV). DIAGNOSIS AND INTERVENTIONS: The patient is a middle-aged male, with acute onset, previous history of hypertension, cholecystectomy, intestinal obstruction, spontaneous renal rupture, etc. For this complaint, the manifestations are mainly blurred vision with convulsion and transient disturbance of consciousness. In 1 day of treatment, these symptoms were relieved, and he was diagnosed as PRES combined with the cranial imaging. The AAV of the patient was confirmed by spleen pathology. OUTCOMES: Despite the relief of most symptoms in 1 day of symptomatic treatment, it is highly likely that the patient eventually died of AAV, it is highly likely that the patient eventually died of AAV which will invade the vascular system due to the failure to treat the primary disease in time. LESSONS: For patients diagnosed as PRES, the punctual identification of cause should be performed, so as to diagnose and correct the cause and primary disease as soon as possible, accompanied with the dynamical observation of the relevant indicators for suspected patients to avoid systemic organ failure.

Cyclic Ether-Water Hybrid Electrolyte-Guided Dendrite-Free Lamellar Zinc Deposition by Tuning the Solvation Structure for High-Performance Aqueous Zinc-Ion Batteries.

The serious zinc dendrites and poor cyclability at high cathode loading owing to the strong solvation effect of traditional aqueous electrolytes are the main bottlenecks to the development of aqueous rechargeable zinc-ion batteries (ARZIBs). Here, we design an ether-water hybrid zinc-ion electrolyte with bifunctional roles of not only unplugging the dendrites bottleneck at the Zn anode but also extending the cycle life at high cathode loading. A cyclic ether (1,4-dioxane (DX)) is incorporated into traditional ZnSO4-based electrolytes to finely tune the solvation sheath of Zn2+. DX is found to guide the deposition orientation of zinc along the (002) plane, leading to not a dendritic structure but distinctively dense lamellar deposition due to the stronger affinity of the cyclic DX molecules toward Zn(002) than that of water, which is proven by density functional theory calculations. The cycling lifespan of the Zn anode extends up to over 600 h at 5.0 mA cm-2 and maintains extremely high Coulombic efficiency of 99.8%, thereby further enabling the Zn-MnO2 full cells to stably cycle at an ultrahigh mass loading of 9.4 mg cm-2, paving the way to their practical applications. This work also provides a novel electrolyte regulating solution for other aqueous multivalent metal-ion batteries.

Clock-drawing test in vascular mild cognitive impairment: Validity of quantitative and qualitative analyses.

INTRODUCTION: The clock-drawing test (CDT) has been used as a screening tool to identify cognitive deficit in patients with dementia. However, it has not been extensively evaluated for categorizing patients with vascular mild cognitive impairment (vMCI). This study aimed to examine the discrimination of vMCI using various CDT scoring methods. METHOD: A total of 120 vMCI patients and 119 normal control (NC) subjects were tested using three CDT quantitative scoring systems: the one from the Montreal Cognitive Assessment (MoCA) (CDT3) and the systems of Rouleau (CDT10) and Babins (CDT18). We used a revised scoring method to evaluate the effectiveness in differentiating vMCI patients from NC subjects, which combined the CDT10 quantitative score and three qualitative errors with a significantly higher prevalence in vMCI group (called hereinafter CDTcomb, including CDTcomb13 and CDTcomb16 based on different weights of the three error types). The sensitivity and specificity of the CDT methods were determined by the receiver operating characteristic (ROC) curve. The results of the scoring systems were compared with those of the Mini-Mental State Examination (MMSE). RESULTS: The results of the ROC analyses with the CDT3, CDT10, and CDT18 systems produced a sensitivity of 71.1%, 81.8%, and 60.3%, and a specificity of 66.12%, 58.68%, and 73.55%, respectively, for the diagnosis of vMCI. Compared with the separate MMSE score, the combination of MMSE with the CDT3, CDT10 and CDT18 scores did not increase the sensitivity and specificity. When three qualitative errors were incorporated into the CDT10 quantitative score, CDTcomb13 and CDTcomb16 provided a sensitivity of 87.6% and 86.78%, and a specificity of 74.79% and 80.67%, respectively, in differentiating vMCI patients from the NC group. CONCLUSION: Our findings suggest that the combination of CDT quantitative score with qualitative observations of the clock-drawing errors can provide a better discrimination between vMCI patients and cognitively normal subjects.

Enhancement of using combined packing materials on the removal of mixed sulfur compounds in a biotrickling filter and analysis of microbial communities.

BACKGROUND: Packing materials is a critical design consideration when employing biological reactor to treat malodorous gases. The acidification of packing bed usually results in a significant drop in the removal efficiency. In the present study, a biotrickling filter (BTF2) packed with plastic balls in the upper layer and with lava rocks in the bottom layer, was proposed to mitigate the acidification. RESULTS: Results showed that using combined packing materials efficiently enhanced the removal performance of BTF2 when compared with BTF1, which was packed with sole lava rocks. Removal efficiencies of more than 92.5% on four sulfur compounds were achieved in BTF2. Average pH value in its bottom packing bed was about 4.86, significantly higher than that in BTF1 (2.85). Sulfate and elemental sulfur were observed to accumulate more in BTF1 than in BTF2. Analysis of principal coordinate analysis proved that structure of microbial communities in BTF2 changed less after the shutdown but more when the initial pH value was set at 5.5. Network analysis of significant co-occurrence patterns based on the correlations between microbial taxa revealed that BTF2 harbored more diverse microorganisms involving in the bio-oxidation of sulfur compounds and had more complex interactions between microbial species. CONCLUSIONS: Results confirmed that using combined packing materials effectively improved conditions for the growth of microorganisms. The robustness of reactor against acidification, adverse temperature and gas supply shutdown was greatly enhanced. These provided a theoretical basis for using mixed packing materials to improve removal performance.

Enhanced biological removal of intermittent VOCs and deciphering the roles of sodium alginate and polyvinyl alcohol in biofilm formation.

Developing a robust biofilm is a prerequisite for a biotrickling filter to obtain the good performance in removing volatile organic compounds (VOCs). But the biofilm formation can be seriously disturbed under intermittent loading condition due to carbon starvation stress in idle time. In this study, a biotrickling filter, with its packing materials being modified by 3% sodium alginate and 5% polyvinyl alcohol (v/v = 1:3), was employed to treat intermittent VOCs. Results showed that the removal efficiencies of toluene, ethylbenzene, p-xylene, m-xylene, and o-xylene was significantly enhanced in the BTF compared to the control one. Under relatively lower inlet loading, nearly complete removal of the five pollutants was achieved. A quantitative analysis showed that the concentration of total organic compound (TOC) in the leachate maintained at a high level, and had a strongly positive correlation with the divergence of microbial communities. The capacity of biofilm formation in the BTF was approximately four-fold higher than the control BTF, while the quantity of EPS secreted was more than ten-fold. EPS comprised largely of protein, and to less extent, polysaccharide. The biofilm formed on the modified packing materials maintained higher levels of microbial diversity and stability, even when modifiers were complete depleted or the VOCs inlet loading was increased. This study highlights the importance of packing materials for reducing the gap in performance between laboratory and industrial applications of BTFs.

Structure and predictive functional profiling of microbial communities in two biotrickling filters treated with continuous/discontinuous waste gases.

Two biotrickling filters were operated in continuous (BTF1) and discontinuous (BTF2) modes at a constant empty bed residence time of 60 s for 60 days. From day 60, the operation mode of each BTF was oppositely switched. Higher removal efficiencies of five aromatic pollutants were recorded with BTF1 (> 77.2%). The switch in the operation mode did not alter the removal performance of BTF1. Comparatively, BTF2 was not successfully acclimated in the discontinuous operation mode. Once the mode had been switched to continuous mode, the removal efficiencies of BTF2 on all pollutants increased drastically and finally exceeded the values observed in BTF1, with the single exception of p-xylene. Principle coordinate analysis and analysis of similarities (ANOSIM) showed that the structure of the microbial communities differed considerably between both BTFs (R = 1.000, p < 0.01) as well as before and after the switch in BTF2 (R = 0.996, p < 0.01). The random forest model demonstrated that Mycobacterium, Burkholderia, and Comamonas were the three most important bacterial genera contributing to the differences in microbial communities between the two BTFs. Metagenomics inferred by PICUSt (phylogenetic investigation of communities by reconstruction of unobserved states) indicated that BTF2 had high degradation potential for aromatic pollutants, although those genes involved in biofilm formation were less active in BTF2 than those in BTF1.

Effect of sertraline in the treatment and prevention of poststroke depression: A meta-analysis.

BACKGROUND: Morbidity of poststroke depression (PSD) remains high worldwide. Additionally, PSD causes multiple sequelae. Although sertraline has been reported to be effective in treating PSD, many studies remain inconsistent. METHODS: PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, Clinical trials. gov, Wan fang Data (Chinese), VIP (Chinese), and CNKI (Chinese) were retrieved from inception to April 2017. Randomized controlled trials (RCTs) and self-controlled trials (SCTs) were recruited, which met the inclusion criteria in our study. The depression rating scores, the incidence of PSD, activities of daily living (ADL), neurological impairment scores, and adverse effects were assessed. RESULTS: Around 11 studies were recruited in our work, including 1258 participants. For trials enrolled, the results were depicted: the reduction of depression rating scores was significant in sertraline groups (WMD -6.38; 95% CI -8.63 to -4.14; P < .00001); the incidence of PSD was significantly lower in sertraline groups (RR 0.48; 95%CI 0.35-0.67; P < .0001); there was obvious improvement of ADL (WMD 11.48; 95% CI 4.18-18.78; P = .002 <0.05) and neurological impairment (WMD -3.44; 95% CI -6.66 to -0.21; P = .04 <0.05); no significant difference between sertraline and control groups in the morbidity of adverse events (RR 0.94; 95% CI 0.83-1.06; P = .33 >0.05). However, in sensitivity analyses, the conclusions of the reduction of depression rating scores and the improvement of ADL were altered. CONCLUSIONS: The study suggests that sertraline has a potentially protective role compared with control groups and demonstrates sertraline is safe. However, the reduction of depression rating scores and the improvement of ADL should be considered carefully.

Role of sodium-hydrogen exchanger isoform 1 in regulating hepatocyte apoptosis induced by hyperammonaemia / Papel de la isoforma 1 del intercambiador iónico de sodio/hidrógeno en la regulación de la apoptosis de hepatocitos inducida por hiperamoniaquemia

Background: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NH4Cl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NH4Cl. Materials and methods: In current studies, intracellular pH (pHi) and NHE1 activity were analyzed using the pHi-sensitive dye BCECF-AM. The results showed that intracellular pH dropped and NHE1 activity increased in hepatocytes under NH4Cl treatment. As expected, decreased pHi induced by NH4Cl was associated with increased apoptosis, low cell proliferation and ATP depletion, which was exacerbated by exposure to the NHE1 inhibitor cariporide. We also found that NH4Cl treatment stimulated PI3K and Akt phosphorylation and this effect was considerably reduced by NHE1 inhibition. Conclusion: This study highlighted the significant role of NHE1 in the regulation of cell apoptosis induced by hyperammonaemia

Antecedentes: La teoría de la «lesión secundaria» de la insuficiencia hepática mostró que la hiperamoniaquemia provocada por la insuficiencia hepática causa mayor deterioro de los hepatocitos. Nuestros anteriores estudios previos han demostrado que los niveles altos de amoníaco en sangre pueden conducir a la apoptosis de los hepatocitos. Como la carga de NH4Cl provocó acidosis metabólica y un aumento de la isoforma 1 del intercambiador de sodio/hidrógeno (NHE1). En este estudio, establecimos un modelo de hepatocitos de hiperamonia para establecer el papel de NHE1 en la regulación de la apoptosis de hepatocitos inducida por NH4Cl. Materiales y métodos: En los estudios actuales, el pH intracelular (pHi) y la actividad del NHE1 se analizaron con el colorante BCECF-AM, sensible al pHi. Los resultados mostraron que el pH intracelular disminuyó y la actividad del NHE1 aumentó en hepatocitos con tratamiento del NH4Cl. Como se esperaba, la disminución del pHi inducido por NH4Cl se relacionó con un aumento de la apoptosis, baja proliferación celular y reducción del ATP, que se exacerbó por la exposición a cariporide, inhibidor del NHE1. También encontramos que el tratamiento del NH4Cl estimuló la fosforilación de PI3K y Akt, y este efecto se redujo considerablemente por la inhibición del NHE1. Conclusión: Este trabajo ha destacado el importante papel del NHE1 en la regulación de la apoptosis celular inducida por hiperamoniaquemia

Role of sodium-hydrogen exchanger isoform 1 in regulating hepatocyte apoptosis induced by hyperammonaemia.

BACKGROUND: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NH4Cl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NH4Cl. MATERIALS AND METHODS: In current studies, intracellular pH (pHi) and NHE1 activity were analyzed using the pHi-sensitive dye BCECF-AM. The results showed that intracellular pH dropped and NHE1 activity increased in hepatocytes under NH4Cl treatment. As expected, decreased pHi induced by NH4Cl was associated with increased apoptosis, low cell proliferation and ATP depletion, which was exacerbated by exposure to the NHE1 inhibitor cariporide. We also found that NH4Cl treatment stimulated PI3K and Akt phosphorylation and this effect was considerably reduced by NHE1 inhibition. CONCLUSION: This study highlighted the significant role of NHE1 in the regulation of cell apoptosis induced by hyperammonaemia.

Removal of benzene, toluene, xylene and styrene by biotrickling filters and identification of their interactions.

Biotrickling filters (BTFs) are becoming very potential means to purify waste gases containing multiple VOC components, but the removal of the waste gases by BTF has been a major challenge due to the extremely complicated interactions among the components. Four biotrickling filters packed with polyurethane foam were employed to identify the interactions among four aromatic compounds (benzene, toluene, xylene and styrene). The elimination capacities obtained at 90% of removal efficiency for individual toluene, styrene and xylene were 297.02, 225.27 and 180.75 g/m3h, respectively. No obvious removal for benzene was observed at the inlet loading rates ranging from 20 to 450 g/m3h. The total elimination capacities for binary gases significantly decreased in all biotrickling filters. However, the removal of benzene was enhanced in the presence of other gases. The removal capacities of ternary and quaternary gases were further largely lowered. High-throughput sequencing results revealed that microbial communities changed greatly with the composition of gases, from which we found that: all samples were dominated either by the genus Achromobacter or the Burkholderia. Different gaseous combination enriched or inhibited some microbial species. Group I includes samples of BTFs treating single and binary gases and was dominated by the genus Achromobacter, with little Burkholderia inside. Group II includes the rest of the samples taken from BTFs domesticated with ternary and quaternary gases, and was dominated by the genus Burkholderia, with little Achromobacter detected. These genera were highly associated with the biodegradation of benzene series in BTFs.

SS31 ameliorates age-related activation of NF-κB signaling in senile mice model, SAMP8.

Aging has been attributed to oxidative stress and inflammatory response, in which NF-κB and Nrf2-ARE signaling pathways play significant roles. Senescence accelerated mouse prone 8 (SAMP8) is generally used an animal model for aging studies. Here, we investigated the NF-κB and Nrf2-ARE signaling pathways in SAMP8 brains at different ages and their responses to SS31 peptide treatment. Thirty six SAMP8 mice were separated into aging groups and SS31-treatment groups. The hippocampus from each mouse was dissected for RNA and protein extraction. Cytokines and ROS levels were measured using ELISA and standardised method. Gene expressions of NF-κB, Nrf2 and HO-1 were measured by RT-qPCR. Total protein amount of NF-κB and HO-1, as well as the concentrations of nuclear and cytoplasmic Nrf2 were measured using Western blots. Our data showed that aging could activate both NF-κB and Nrf2-ARE signaling pathways, which could be suppressed and activated by SS31 treatment respectively. Regression analysis revealed that NF-κB gene expression was the most important parameter predicting aging process and SS31 treatment effects in SAMP8. Our findings suggested that SS31 treatment may modulate the inflammatory and oxidative stress status of the aged brains and exert protective effects during brain aging.

Comparison of Removal Behavior of Two Biotrickling Filters under Transient Condition and Effect of pH on the Bacterial Communities.

Although biotrickling filters (BTFs) applied under acidic condition to remove H2S from waste gases have been reported, the removal behavior of the acidic BTF under transient condition which was normal in most industry processes, and corresponding bacterial community have not been thoroughly studied. In the present study, two BTFs were run under neutral (BTFn) and acidic (BTFa) conditions, respectively. The results revealed that the removal performance of BTFa under transient condition was superior to that of BTFn; the maximum H2S eliminating capacities (ECs) achieved by BTFa and BTFn were 489.9 g/m3 h and 443.6 g/m3 h, respectively. High-throughput sequencing suggested that pH was the critical factor and several other factors including nutrient and the inlet loadings also had roles in shaping bacterial community structure. Acidithiobacillus was the most abundant bacterial group. The results indicated that BTF acclimation under acidic condition may facilitate generating microbial community with high H2S-degrading capability.

Genetic Map Construction and Quantitative Trait Locus (QTL) Detection of Six Economic Traits Using an F2 Population of the Hybrid from Saccharina longissima and Saccharina japonica.

Saccharina (Laminaria) is one of the most important economic seaweeds. Previously, four genetic linkage maps of Saccharina have been constructed and five QTLs have been identified. However, they were not enough for its breeding. In this work, Saccharina longissima (♀) and Saccharina japonica (♂), which showed obvious differences in morphology and genetics, were applied in hybridization to yield the F2 mapping population with 102 individuals. Using these 102 F2 hybrids, the genetic linkage map of Saccharina was constructed by MapMaker software based on 37 amplified fragment length polymorphisms (AFLPs), 22 sequence-related amplified polymorphisms (SRAPs) and 139 simple sequence repeats (SSRs) markers. Meanwhile, QTL analysis was performed for six economic traits. The linkage map constructed in this research consisted of 422 marker loci (137 AFLPs, 57 SRAPs and 228 SSRs), which formed 45 linkage groups (LGs) with an average marker space of 7.92 cM; they spanned a total length of 2233.1 cM, covering the whole estimated genome size. A total of 29 QTLs were identified for six economic traits, which explained 1.06 to 64.00% of phenotypic variation, including three QTLs for frond length (FL) and raw weight (RW), five QTLs for frond width (FW), two QTLs for frond fascia width (FFW) and frond thickness (FT), and fourteen QTLs for base shape (BS). The results of this research will improve the breeding efficiency and be beneficial for marker-assisted selection (MAS) schemes in Saccharina breeding.

[The role of NO resulted from neuronal nitric oxide synthase in the metabotropic glutamate receptor2/3 mediated-brain ischemic tolerance].

AIM: To explore the role of nitric oxide (NO) resulted from nNOS in the mGluR2/3 mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP), the present study is undertaken to observe the influences of alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the expression of nNOS during the induction of the brain ischemic tolerance based on confirming the blocking effect of MTPG on the induction of the tolerance. METHODS: Thirty-six Sprague-Dawley rats, whose vertebral arteries were permanently occluded, were randomly divided into sham, CIP, ischemic insult, CIP+ ischemic insult, MTPG+ CIP and MTPG+ CIP+ ischemic insult groups. Thionin staining and immunohistochemistry were used for neuropathological evaluation and assay of nNOS expression in the hippocampal CA1 subregion of the rats. RESULTS: The expression of nNOS showed moderate and extreme up-regulation in the CIP and ischemia groups, respectively, compared to the sham group. The preceded CIP blocked in certain extent the extreme up-regulation of nNOS induced by brain ischemia in CIP + ischemia group. Administration of MTPG via lateral cerebral ventricle 20 min before CIP blocked the up-regulation of nNOS induced by CIP, but had no influence on the pyramidal neuronal survival. While in the MTPG+ CIP+ ischemic insult group, the expression of nNOS was stronger than that in the MTPG + CIP group, and the up-regulation was accompanied with obvious delayed neuronal death. Discussion concerned illustrated that the relative intensive up-regulation of nNOS in this group might be attributed to brain ischemia other than MTPG. CONCLUSION: NO resulted from nNOS participated the induction of mGluR2/3 mediated-brain ischemic tolerance as a downstream molecule of activation of mGluR2/3 during CIP.

Nitric oxide participates in the induction of brain ischemic tolerance via activating ERK1/2 signaling pathways.

The present study was undertaken to observe in vivo changes of expression and phosphorylation of ERK1/2 proteins during brain ischemic preconditioning and effects of inhibiting generation of nitric oxide (NO) on the changes to determine the role of ERKs in the involvement of NO participating in the acquired tolerance. Fifty-five Wistar rats were used. Brain ischemic preconditioning was performed with four-vessel occlusion for 3 min. Total ERK1/2 proteins and phospho-ERK1/2 in the CA1 hippocampus were assayed with Western immunoblot. Total ERK1/2 proteins did not change in period from 5 min to 5 days of reperfusion after preconditioning stimulus. While the level of phospho-ERK1/2 increased obviously to 223, 237, 300, 385 and 254% of sham level at times of 5 min, 2 h, 1, 3 and 5 days after preconditioning stimulus, respectively (P < 0.01). Administration of L-NAME, an inhibitor of NO synthase, 30 min prior to preconditioning stimulus failed to induce change in total ERK1/2 proteins (P > 0.05). However, phospho-ERK1/2 increased only to 138 and 176% of sham level at 2 h and 3 days after preconditioning stimulus, respectively, when animals were pretreated with L-NAME. The magnitudes of the increase were obviously low compared with those (237 and 385%) in animals untreated with L-NAME at corresponding time points (P < 0.01), which indicated that phosphorylation of ERK1/2 normally induced by preconditioning stimulus was blocked apparently by administration of L-NAME. The results suggested that phosphorylation of ERK1/2, rather than synthesis of ERK1/2 proteins, was promoted in brain ischemic preconditioning, and that the promotion was partly mediated by NO signal pathway.

[The effect of time parameters of cerebral ischemic preconditioning on its protective effect against global cerebral ischemic injury in rats].

AIM: To investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult. METHODS: Four-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus. RESULTS: No DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05). CONCLUSION: Although the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.