Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats.

Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 µM. The removal of extracellular Ca2+ or blockade of N-and P/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.

Impact of Recurrent Mitral Regurgitation on Left Ventricular Mass Regression and Cardiac Events following Mitral Valve Repair.

BACKGROUND: Mitral valve regurgitation results in volume overload, followed by left ventricular remodeling. Variation of reverse remodeling following mitral repair influences the clinical outcomes. We aimed to evaluate the association between recurrent mitral regurgitation and mass regression following mitral valve repair and the impact on major adverse cardiovascular events. METHODS: A retrospective cohort study was conducted on 164 consecutive patients with severe mitral regurgitation who underwent elective mitral valve repair. Subgroups were classified based on the presence of recurrent mitral regurgitation exceeding moderate severity. The hemodynamic parameters were evaluated according to geometry, mass, and function with Doppler echocardiography before and after surgery. Cox regression analysis was performed to evaluate the association between hemodynamics and mass regression and clinical outcomes. RESULTS: The results for MR indicated 110 cases with non-recurrent MR and 54 with recurrent MR, along with 31 major adverse cardiovascular events. The tracked echocardiographic results revealed less reduction in dimension and volume, along with less mass regression in the recurrent MR subgroup. Significant differences were revealed in the relative change of the LV end-diastolic volume index and relative mass regression between subgroups. The relative change in the LVEDVI was proportionally correlated with relative mass regression. Cox regression analysis identified correlations with major adverse cardiovascular events, including suture annuloplasty, recurrent mitral regurgitation, tracked LV mass, relative LV mass regression, and systolic dysfunction. CONCLUSION: LV mass regression and relative change of the LV end-diastolic volume could be risk predictors of recurrent mitral regurgitation. The extent of LV mass regression is correlated with adverse cardiac events.

Lappaconitine inhibits glutamate release from rat cerebrocortical nerve terminals by suppressing Ca2+ influx and protein kinase A cascade.

The inhibition of the excessive release of glutamate in the brain has emerged as a promising new option for developing therapeutic strategies for neurodegenerative disorders. This study investigated the effect and mechanism of lappaconitine, a diterpenoid alkaloid found in species of Aconitum, on glutamate release in rat cerebral cortex nerve terminals (synaptosomes). Here, we report that in the rat cortical synaptosomal preparation, lappaconitine reduced the K+ channel blocker 4-aminopyridine (4-AP)-evoked Ca2+-dependent release of glutamate. The inhibitory effect of lappaconitine on the evoked glutamate release was blocked by the vesicular transporter inhibitor bafilomycin A1 and calcium-chelating agent ethylene glycol tetraacetic acid (EGTA), but was unaffected by exposure to the glutamate transporter inhibitor dl-threo-beta-benzyloxyaspartate (dl-TBOA). The depolarization-induced elevation of cytosolic calcium concentration ([Ca2+]c) was inhibited by lappaconitine, while the 4-AP-mediated depolarization of the synaptosomal membrane potential was not affected. The inhibition of glutamate release by lappaconitine was markedly decreased in synaptosomes pretreated with the Cav2.3 (R-type) channel blocker SNX-482 or the protein kinase A inhibitor H89. Nevertheless, the lappaconitine-mediated inhibition of glutamate release was not abolished by the intracellular Ca2+-release inhibitors dantrolene and CGP37157. Lappaconitine also significantly decreased the 4-AP-induced phosphorylation of PKA and SNAP-25, a presynaptic substrate for PKA. Our data suggest that lappaconitine reduces Ca2+ influx through R-type Ca2+ channels, subsequently reducing the protein kinase A cascade to inhibit the evoked glutamate release from rat cerebral cortex nerve terminals.

Neferine, an Alkaloid from Lotus Seed Embryos, Exerts Antiseizure and Neuroprotective Effects in a Kainic Acid-Induced Seizure Model in Rats.

Current anti-seizure drugs fail to control approximately 30% of epilepsies. Therefore, there is a need to develop more effective anti-seizure drugs, and medicinal plants provide an attractive source for new compounds. This study aimed to evaluate the possible anti-seizure and neuroprotective effects of neferine, an alkaloid from the lotus seed embryos of Nelumbo nucifera, in a kainic acid (KA)-induced seizure rat model and its underlying mechanisms. Rats were intraperitoneally (i.p.) administrated neferine (10 and 50 mg/kg) 30 min before KA injection (15 mg/kg, i.p.). Neferine pretreatment increased seizure latency and reduced seizure scores, prevented glutamate elevation and neuronal loss, and increased presynaptic protein synaptophysin and postsynaptic density protein 95 expression in the hippocampi of rats with KA. Neferine pretreatment also decreased glial cell activation and proinflammatory cytokine (interleukin-1ß, interleukin-6, tumor necrosis factor-α) expression in the hippocampi of rats with KA. In addition, NOD-like receptor 3 (NLRP3) inflammasome, caspase-1, and interleukin-18 expression levels were decreased in the hippocampi of seizure rats pretreated with neferine. These results indicated that neferine reduced seizure severity, exerted neuroprotective effects, and ameliorated neuroinflammation in the hippocampi of KA-treated rats, possibly by inhibiting NLRP3 inflammasome activation and decreasing inflammatory cytokine secretion. Our findings highlight the potential of neferine as a therapeutic option in the treatment of epilepsy.

The impact of dental therapy timelines and irradiation dosages on osteoradionecrosis in oral cancer patients: A population-based cohort study.

OBJECTIVES: This study aimed to investigate how different timelines of various dental therapies were related to osteoradionecrosis development under consideration of radiotherapy dosage in patients with oral cancer. MATERIALS AND METHODS: A total of 7,107 oral cancer patients were enrolled, including 88 osteoradionecrosis patients treated with low radiotherapy dosages (<60 Gy) or high radiotherapy dosages (≥60 Gy), from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan. Cox proportional hazard regression was used to compare the osteoradionecrosis risk of various dental treatment timelines under different irradiation dosages. RESULTS: In the oral cancer population with low irradiation dosages (<60 Gy), performing periodontal therapy combined with irradiation significantly raised the risk of osteoradionecrosis by 2.21-fold. Starting radiotherapy within three months after dental surgery greatly increased the risk of developing osteoradionecrosis by 1.87-fold. The oral cancer patients treated with high radiation doses (≥60 Gy) receiving dental surgery within one month prior to radiotherapy had a significantly raised osteoradionecrosis occurrence by 1.60-fold. While the dental surgery was performed during the radiotherapy course, the risk of osteoradionecrosis was greatly increased by 2.21-fold. CONCLUSION: For oral cancer patients, performing dental surgery within three months before radiotherapy might significantly induce osteoradionecrosis. Patients that were treated with high irradiation dosages (≥60 Gy) had a higher tendency to develop osteoradionecrosis if they received dental surgery during radiotherapy. Those who were treated with low radiation dosages (<60 Gy) and received periodontal therapy during radiotherapy might have an increased risk in developing osteoradionecrosis.

The impact of timing and modalities of dental prophylaxis on the risk of 5-fluorouracil-related oral mucositis in patients with head and neck cancer: a nationwide population-based cohort study.

PURPOSE: This study investigated the impact of dental prophylaxis on 5-fluorouracil (5-FU)-related oral mucositis (OM) according to the head and neck cancer (HNC) locations and treatment times. METHODS: A total of 13,969 HNC participants, including 482 5-FU-related OM subjects and 13,487 comparisons were enrolled from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2008. All subjects were stratified into subgroups based on the times to perform chlorhexidine use, scaling, and fluoride application before 5-FU administration. The dental prophylaxis related to 5-FU-related OM was estimated by multiple logistic regression and represented with odds ratio (OR) and 95% confidence interval (CI). RESULTS: Fluoride gel application and scaling significantly impacted on OM development (p < 0.001), and the joint effect of fluoride gel and scaling induced 5-FU-related OM (OR = 3.46, 95% CI = 2.39-5.01). The risk of OM was raised 2.25-fold as scaling within 3 weeks before 5-FU-related chemotherapy (95% CI = 1.81-2.81), and a 3.22-fold increased risk of OM while fluoride gel was applied during 5-FU-related treatment (95% CI = 1.46-7.13). CONCLUSION: Dental prophylaxis significantly affected 5-FU-related OM in the HNC population. A short interval between dental scaling or fluoride application and 5-FU administration may be associated with higher prevalence of OM. Scaling simultaneously combined with chlorohexidine promoted 5-FU-related OM in specific HNC patients excluding the oral cancer and nasopharyngeal cancer population. Proper timing of the prophylactic dental treatments prior to 5-FU therapy could reduce the risk to develop 5-FU-related OM.

Silymarin Inhibits Glutamate Release and Prevents against Kainic Acid-Induced Excitotoxic Injury in Rats.

Silymarin, a polyphenoic flavonoid derived from the seeds of milk thistle (Silybum marianum), exhibits neuroprotective effects. In this study, we used a model of rat cerebrocortical synaptosomes to investigate whether silymarin affects the release of glutamate, an essential neurotransmitter involved in excitotoxicity. Its possible neuroprotective effect on a rat model of kainic acid (KA)-induced excitotoxicity was also investigated. In rat cortical synaptosomes, silymarin reduced glutamate release and calcium elevation evoked by the K+ channel blocker 4-aminopyridine but did not affect glutamate release caused by the Na+ channel activator veratridine or the synaptosomal membrane potential. Decreased glutamate release by silymarin was prevented by removal of extracellular calcium and blocking of N- and P/Q-type Ca2+ channel or extracellular signal-regulated kinase 1/2 (ERK1/2) but not by blocking of intracellular Ca2+ release. Immunoblotting assay results revealed that silymarin reduced 4-aminopyridine-induced phosphorylation of ERK1/2. Moreover, systemic treatment of rats with silymarin (50 or 100 mg/kg) 30 min before systemic KA (15 mg/kg) administration attenuated KA-induced seizures, glutamate concentration elevation, neuronal damage, glial activation, and heat shock protein 70 expression as well as upregulated KA-induced decrease in Akt phosphorylation in the rat hippocampus. Taken together, the present study demonstrated that silymarin depressed synaptosomal glutamate release by suppressing voltage-dependent Ca2+ entry and ERK1/2 activity and effectively prevented KA-induced in vivo excitotoxicity.

Management of Venous Thromboembolisms: Part II. The Consensus for Pulmonary Embolism and Updates.

Pulmonary embolism (PE) is a potential life-threatening condition and risk-adapted diagnostic and therapeutic management conveys a favorable outcome. For patients at high risk for early complications and mortality, prompt exclusion or confirmation of PE by imaging is the key step to initiate and facilitate reperfusion treatment. Among patients with hemodynamic instability, systemic thrombolysis improves survival, whereas surgical embolectomy or percutaneous intervention are alternatives in experienced hands in scenarios where systemic thrombolysis is not the best preferred thromboreduction measure. For patients with suspected PE who are not at high risk for early complications and mortality, the organized approach using a structured evaluation system to assess the pretest probability, the age-adjusted D-dimer cut-offs, the appropriate selection of imaging tools, and proper interpretation of imaging results is important when deciding the allocation of treatment strategies. Patients with PE requires anticoagulation treatment. In patients with cancer and thrombosis, low-molecular-weight heparin (LMWH) used to be the standard regimen. Recently, three factor Xa inhibitors collectively show that non-vitamin K oral anticoagulants (NOACs) are as effective as LMWH in four randomized clinical trials. Therefore, NOACs are suitable and preferred in most conditions. Finally, chronic thromboembolic pulmonary hypertension is the most disabling long-term complication of PE. Because of its low incidence, the extra caution should be given when managing patients with PE.

Prediction of the development of acute kidney injury following cardiac surgery by machine learning.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication that results in increased morbidity and mortality after cardiac surgery. Most established prediction models are limited to the analysis of nonlinear relationships and fail to fully consider intraoperative variables, which represent the acute response to surgery. Therefore, this study utilized an artificial intelligence-based machine learning approach thorough perioperative data-driven learning to predict CSA-AKI. METHODS: A total of 671 patients undergoing cardiac surgery from August 2016 to August 2018 were enrolled. AKI following cardiac surgery was defined according to criteria from Kidney Disease: Improving Global Outcomes (KDIGO). The variables used for analysis included demographic characteristics, clinical condition, preoperative biochemistry data, preoperative medication, and intraoperative variables such as time-series hemodynamic changes. The machine learning methods used included logistic regression, support vector machine (SVM), random forest (RF), extreme gradient boosting (XGboost), and ensemble (RF + XGboost). The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC). We also utilized SHapley Additive exPlanation (SHAP) values to explain the prediction model. RESULTS: Development of CSA-AKI was noted in 163 patients (24.3%) during the first postoperative week. Regarding the efficacy of the single model that most accurately predicted the outcome, RF exhibited the greatest AUC (0.839, 95% confidence interval [CI] 0.772-0.898), whereas the AUC (0.843, 95% CI 0.778-0.899) of ensemble model (RF + XGboost) was even greater than that of the RF model alone. The top 3 most influential features in the RF importance matrix plot were intraoperative urine output, units of packed red blood cells (pRBCs) transfused during surgery, and preoperative hemoglobin level. The SHAP summary plot was used to illustrate the positive or negative effects of the top 20 features attributed to the RF. We also used the SHAP dependence plot to explain how a single feature affects the output of the RF prediction model. CONCLUSIONS: In this study, machine learning methods were successfully established to predict CSA-AKI, which determines risks following cardiac surgery, enabling the optimization of postoperative treatment strategies to minimize the postoperative complications following cardiac surgeries.

Clinical significance of quantitative assessment of right ventricular glucose metabolism in patients with heart failure with reduced ejection fraction.

PURPOSE: Dynamic 18F-fluorodeoxyglucose (FDG) PET can be used to quantitatively assess the rate of myocardial glucose uptake (MRGlu). The aim of this study was to evaluate the clinical significance and prognostic value of right ventricular (RV) MRGlu in patients with coronary artery disease and heart failure with reduced ejection fraction. METHODS: Patients with left ventricular ejection fraction (LVEF) ≤ 40% were consecutively enrolled for FDG PET between November 2012 and May 2017. Global LV and RV MRGlu (µmol/min/100 g) were analyzed. Outcome events were independently assessed using electronic medical records to determine hospitalization for revascularization, new-onset ischemic events, heart failure, cardiovascular, and all-cause death. Differences between LV and RV MRGlu and associations with clinical characteristics and echocardiographic data were evaluated. Associations among FDG PET findings and outcomes were analyzed using Kaplan-Meier survival analysis. RESULTS: Seventy-five patients (mean age 62.2 ± 12.7 years, male 85.3%, LVEF 19.3 ± 8.6%) were included for analysis. The mean glucose utilization ratio of RV-to-LV (RV/LV MRGlu) was 89.5 ± 264.9% (r = 0.77, p < 0.001). Positive correlations between RV MRGlu and maximal tricuspid regurgitation peak gradient (r = 0.28, p = 0.033) and peak tricuspid regurgitation jet velocity (r = 0.29, p = 0.021) were noted. LVEF was positively correlated with LV MRGlu (r = 0.27, p = 0.018), but negatively correlated with end-diastolic volume (r = - 0.37, p = 0.001), end-systolic volume (r = - 0.54, p < 0.001), and RV/LV MRGlu (r = - 0.40, p < 0.001). However, RV MRGlu was not well correlated with LVEF. Forty-three patients received revascularization procedures after FDG PET, and 13 patients died in a mean follow-up period of 496 ± 453 days (1-1788 days), including nine cardiovascular deaths. Higher RV and LV MRGlu values, LVEF ≤ 16% and LV end-diastolic volume ≥ 209 ml of gated-PET were associated with poor overall survival and cardiac outcomes. CONCLUSIONS: In patients with coronary artery disease and ischemic cardiomyopathy, RV glucose utilization was positively correlated with RV pressure overload, but not LVEF. Global LV and RV MRGlu, LVEF, and LV end-diastolic volume showed significant prognostic value.

Minimally Invasive coronary surgery compared to STernotomy coronary artery bypass grafting: The MIST trial.

RATIONALE: Minimally invasive cardiac surgery has emerged as a safe alternative to standard cardiac surgery. Minimally invasive coronary surgery (MICS CABG) was developed to allow adequate exposure and complete revascularization in CABG from a small thoracotomy incision without cardiopulmonary bypass. Multiple studies have reported significant shorter length of hospital stay and earlier postoperative physical recovery for MICS CABG patients when compared to sternotomy CABG patients. However, there have been no convincing clinical trials that demonstrate improvement in post-operative quality of life for patients who undergo MICS CABG. STUDY DESIGN: The Minimally Invasive Coronary Surgery compared to Sternotomy Coronary Artery Bypass Grafting (MIST) trial is a multi-centered, prospective randomized controlled trial that compares the quality of life and recovery in the early post-operative period between patients undergoing MICS CABG versus patients undergoing sternotomy CABG. Patients will be randomized either to the MICS CABG group or the sternotomy CABG group, and the target enrollment is 88 patients per group. The primary outcome is quality of life assessment performed by SF-36 questionnaire at 1 month. CONCLUSION: The MIST trial is the first prospective study that compares the quality of life between MICS CABG and sternotomy CABG patients. The results of this trial may enhance the procedural desirability of MICS CABG by patients and provide an incentive for surgeons and institutions to increase the availability of MICS CABG in suitable patients.

Neuroprotective and anti-inflammatory effects of lidocaine in kainic acid-injected rats.

Lidocaine, the most commonly used local anesthetic, inhibits glutamate release from nerve terminals. Given the involvement of glutamate neurotoxicity in the pathogenesis of various neurological disorders, this study investigated the role of lidocaine in hippocampal neuronal death and inflammatory events induced by an i.p. injection of kainic acid (KA) (15 mg/kg), a glutamate analog. The results showed that KA significantly led to neuronal death in the CA3 pyramidal layers of the hippocampus and this effect was attenuated by the systemic administration of lidocaine (0.8 or 4 mg/kg, i.p.) 30 min before KA injection. Moreover, KA-induced microglia activation and gene expression of proinflammatory cytokines, namely, interleukin-1ß, interleukin-6, and tumor necrosis factor-α, in the hippocampus were reduced by the lidocaine pretreatment. Altogether, the results suggest that lidocaine can effectively treat glutamate excitotoxicity-related brain disorders.

Protective effects of bupivacaine against kainic acid-induced seizure and neuronal cell death in the rat hippocampus.

The excessive release of glutamate is a critical element in the neuropathology of epilepsy, and bupivacaine, a local anesthetic agent, has been shown to inhibit the release of glutamate in rat cerebrocortical nerve terminals. This study investigated whether bupivacaine produces antiseizure and antiexcitotoxic effects using a kainic acid (KA) rat model, an animal model used for temporal lobe epilepsy, and excitotoxic neurodegeneration experiments. The results showed that administering bupivacaine (0.4 mg/kg or 2 mg/kg) intraperitoneally to rats 30 min before intraperitoneal injection of KA (15 mg/kg) increased seizure latency and reduced the seizure score. In addition, bupivacaine attenuated KA-induced hippocampal neuronal cell death, and this protective effect was accompanied by the inhibition of microglial activation and production of proinflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in the hippocampus. Moreover, bupivacaine shortened the latency of escaping onto the platform in the Morris water maze learning performance test. Collectively, these data suggest that bupivacaine has therapeutic potential for treating epilepsy.

Intraoperative Measurement of Fractional Flow Reserve in Off-Pump Coronary Artery Bypass: A Pilot Study.

BACKGROUNDS: Fractional flow reserve of myocardium (FFRmyo) is a functional study of significant coronary artery stenosis, defined as the ratio of the pressure distal to the stenosis (poststenosis) divided by the pressure of aortic root (prestenosis). Instead of cath laboratory, we could measure it in operating room for off-pump coronary artery bypass (OPCAB) surgery and here shared our methods in the pilot study. METHODS AND RESULTS: We used needles, catheters, and pressure tracing but without guidewires or fluoroscopy to measure FFRmyo during OPCAB. In February 2010, we conducted the pilot study and collected 32 anastomosis data from 10 patients. Without revising the anastomosis plans based on coronary angiographies, 24 FFRmyo of the 32 anastomoses (75%) were less than 0.75, which represented significant functional stenosis. The FFRmyo measurements did not lead to any adverse events. CONCLUSION: The measurement of fractional flow reserve in OPCAB is safe and feasible. It can serve as a functional assessment of coronary artery stenosis in adjuvant to conventional coronary angiography.

Antimicrobial effect of continuous lidocaine infusion in a Staphylococcus aureus-induced wound infection in a mouse model.

Continuous infusion of local anesthetics in surgical wounds has been shown to be an effective technique for postoperative analgesia. To investigate the potential antimicrobial effect of continuous local anesthetic infusion, we adapted a mouse model of surgical wound infection to examine effects on antibacterial response. Forty male BALB/c mice were randomized into 2 groups. An incision wound was made over the dorsal flank and instilled with Staphylococcus aureus. An osmotic pump was then implanted to deliver either 0.9% NaCl or 2% lidocaine continuously. Each wound was cultured postoperatively at 2 days, and the colony count of S. aureus was determined. Results showed that the number of colony-forming units of S. aureus measured in wounds treated with lidocaine displayed a nearly 10-fold reduction compared to the wounds in the saline group (P=0.009). The demonstrated antibacterial activity indicates that local anesthetic infusion may play a role in prophylaxis for surgical wound infections.

Videoscope-assisted cardiac surgery.

Videoscope-assisted cardiac surgery (VACS) offers a minimally invasive platform for most cardiac operations such as coronary and valve procedures. It includes robotic and thoracoscopic approaches and each has strengths and weaknesses. The success depends on appropriate hardware setup, staff training, and troubleshooting efficiency. In our institution, we often use VACS for robotic left-internal-mammary-artery takedown, mitral valve repair, and various intra-cardiac operations such as tricuspid valve repair, combined Maze procedure, atrial septal defect repair, ventricular septal defect repair, etc. Hands-on reminders and updated references are provided for reader's further understanding of the topic.

Effects of conditioning with sevoflurane before reperfusion on hippocampal ischemic injury and insulin-like growth factor-1 expression in rats.

Sevoflurane pre-conditioning before ischemia can reduce ischemia-reperfusion injuries in cardiac, pulmonary and cerebral tissues. It is uncertain whether sevoflurane conditioning before reperfusion has similar protective effects on neuronal injuries. In this study, we explored the effect of sevoflurane conditioning (at concentrations of 1.5%, 2.4% or 3.0%) on the morphology and molecular mechanisms of the hippocampal CA1 region in male Sprague-Dawley rats subjected to global cerebral ischemia. We determined the pathological results by hematoxylin and eosin (H&E) staining and examined the mRNA levels of insulin-like growth factor-1 (IGF-1) and protein levels of p-JNK1/2 and p-Akt1 in the hippocampus at 24 h, 48 h and 72 h after global cerebral ischemia-reperfusion. Our data showed that O2 post-conditioning and lower dose (1.5%) of sevoflurane did not ameliorate ischemia-induced CA1 injury. However, higher doses of 2.4% and 3.0% sevoflurane post-conditioning alleviated the CA1 injury and enhanced the expression levels of IGF-1 mRNA. Furthermore, sevoflurane post-conditioning inhibited the activations of p-JNK1/2 and enhanced activation of p-Akt1. In conclusion, these results suggest that post-conditioning with sevoflurane at 2.4% and 3.0% ameliorates global cerebral ischemia induced hippocampal CA1 injury by up-regulating the expression of IGF-1 mRNA followed by the activation of p-Akt1 and inhibition of the activation of p-JNK1/2.