scholarly journals Resveratrol ameliorates neuronal apoptosis and cognitive impairment by activating the SIRT1/RhoA pathway in rats after anesthesia with sevoflurane

2021 ◽  
Author(s):  
Qiaoyun Zhou ◽  
Yingfeng Deng ◽  
Xuelian Hu ◽  
Yinye Xu
Keyword(s):  
Signaling Pathway ◽  
Cognitive Dysfunction ◽  
Neuronal Apoptosis ◽  
Neuroprotective Effect ◽  
Postoperative Cognitive Dysfunction ◽  
Male Rats ◽  
Vehicle Group ◽  
Rhoa Signaling ◽  
Bcl2 Expression

Studies have shown that long-term exposure to sevoflurane (SEV) may cause postoperative cognitive dysfunction. This study aimed to investigate the effects of resveratrol (RES) treatment on the changes in the cognitive function of rats after prolonged anesthesia with SEV. Seventy-six adult male rats were used in this study. The SEV model was established under continuous anesthesia for 6 h. Rats were randomly classified into four groups as follows: control, SEV+vehicle, SEV+pre-RES (RES was administered 24 h before establishing the SEV model), and SEV+post-RES (RES was administered 1 h after establishing the SEV model) groups. Neurobehavioral outcomes and the potential mechanism underlying RES-mediated neuroprotection through the SIRT1/RhoA signaling pathway were evaluated. The water maze test showed that long-term exposure to SEV may lead to loss of learning and memory ability in rats (p<0.05). Compared with the SEV+vehicle group, the RES treatment groups showed significantly improved neurobehavioral scores (p<0.05). Additionally, the SEV+pre-RES group had a better outcome than the SEV+vehicle group on days 1 or 2 (p<0.05), unlike the SEV+post-RES group (p>0.05). Western blotting showed that SIRT1, RhoA, and cleaved Caspase-3 (CC3) expression significantly increased in the SEV+vehicle group (p<0.05), while Bcl2 expression decreased (p < 0.05). RES treatment further upregulated SIRT1 and Bcl2 expression and downregulated the expression of RhoA and CC3 (p<0.05). In conclusion, RES treatment improved cognitive dysfunction by reducing neuronal apoptosis in adult rats exposed to SEV. RES partly exerted a neuroprotective effect through the activation of the SIRT1/RhoA signaling pathway.

scholarly journals Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice

2019 ◽  
Vol 28 (6) ◽  
pp. 756-766 ◽  
Author(s):  
Lianhua Zhao ◽  
John H. Zhang ◽  
Prativa Sherchan ◽  
Paul R. Krafft ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Western Blots ◽  
Short And Long Term ◽  
Underlying Mechanisms

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were administered prior to rCTRP9 treatment. Western blots, neurofunctional assessments, immunofluorescence staining, and Fluoro-Jade C (FJC) staining experiments were performed. Administration of rCTRP9 significantly improved both short- and long-term neurofunctional behavior after ICH. RCTRP9 treatment significantly increased the expression of AdipoR1, PI3 K, p-Akt, and Bcl-2, while at the same time was found to decrease the expression of Bax in the brain, which was reversed by inhibition of AdipoR1 and PI3 K. The neuroprotective effect of rCTRP9 after ICH was mediated by attenuation of neuronal apoptosis via the AdipoR1/PI3K/Akt signaling pathway; therefore, rCTRP9 should be further evaluated as a potential therapeutic agent for ICH patients.

scholarly journals Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sher-Wei Lim ◽  
Hui-Chen Su ◽  
Tee-Tau Eric Nyam ◽  
Chung-Ching Chio ◽  
Jinn-Rung Kuo ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Body Weight Loss ◽  
Motor Dysfunction ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Antibacterial Effects ◽  
Neuroprotective Effects ◽  
Tnf Α

Abstract Background Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

scholarly journals Cognitive Dysfunction and Mortality After Carotid Endarterectomy

2021 ◽  
Vol 11 ◽  
Author(s):  
Kristiina Relander ◽  
Marja Hietanen ◽  
Krista Nuotio ◽  
Petra Ijäs ◽  
Irene Tikkala ◽  
...  
Keyword(s):  
Carotid Endarterectomy ◽  
Cognitive Dysfunction ◽  
Prognostic Significance ◽  
Postoperative Cognitive Dysfunction ◽  
Reliable Change Index ◽  
Stable Phase ◽  
Functional Domain ◽  
Cognitive Changes ◽  
Term Survival

Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival.Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders.Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8–13.9, p = 0.002) compared with patients with no cognitive decline.Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.

scholarly journals Lansoprazole-Induced Osteoporosis via IP3R and SOCE Mediated Calcium Signaling Pathway

2021 ◽  
Author(s):  
Zi-Ping Cheng ◽  
Jie-Yang Liu ◽  
Meng-Yuan Ma ◽  
Shi-Yu Sun ◽  
Zeng-qing Ma ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Vehicle Group ◽  
Dependent Manner ◽  
Micro Ct ◽  
Mineral Density ◽  
Calcium Release Channel ◽  
Blood Calcium ◽  
Term Administration

Abstract Background: Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purposes of this study were to establish a murine model of chronic oral administration of PPIs to verify whether PPIs caused bone metabolic impairment, and to investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 mouse osteoblasts.Methods: Lansoprazole-induced bone loss model was employed to investigate the damage effects of PPIs. In vivo, immunohistochemistry and HE staining, micro-CT analysis, blood biochemical tests were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects and related signaling pathway of lansoprazole on MC3T3-E1 cells were investigated by CCK8, EDU kit, flow cytometry, laser confocal, patch clamp, PCR and Western blotting, etc.Results: After 6 months of lansoprazole gavage in ICR mice, micro-CT results showed that compared with the vehicle group, the bone mineral density (BMD) of high-dose group was significantly decreased (P<0.05), and the bone microarchitecture gradually degraded. Biochemical assay of bone serum found that blood calcium and phosphorus were both decreased (P<0.01). We found that long-term administration of lansoprazole impairs skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOC pathway, efctively blocked calcium increase caused by LPZ, thus protecting cell viability.Conclusion: Long-term administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium elevation in osteoblasts in a concentration dependent manner, intracellular calcium ([Ca2+] persisted at a high concentration thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblasts apoptosis.

scholarly journals Exosomes of Antler Mesenchymal Stem Cells Improve Postoperative Cognitive Dysfunction in Cardiopulmonary Bypass Rats through Inhibiting the TLR2/TLR4 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Chun Yang ◽  
Shengnan Sun ◽  
Qi Zhang ◽  
Jia Guo ◽  
Tengfei Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiopulmonary Bypass ◽  
Signaling Pathway ◽  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
Paracrine Factors ◽  
Tlr4 Signaling ◽  
Tlr4 Agonist ◽  
Tlr4 Signaling Pathway

Postoperative cognitive dysfunction (POCD) is a severe complication of cardiopulmonary bypass (CPB) and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cells (MSCs) are multipotent cells that have therapeutic potentials mainly through paracrine action via secreting growth factors and cytokines. Exosomes are one of the important paracrine factors and have been reported as potential cell-free therapy for the treatment of autoimmune and central nervous system disorders. In this study, we examined exosomes derived from antler MSCs (AMSCs) of POCD rats after CPB and evaluated their potential regulatory mechanisms. AMSC-derived exosomes reduced neurological damage and brain damage and prevent apoptosis in CPB rats. Furthermore, AMSC-derived exosomes were found to reduce hippocampal neuronal apoptosis and the expression of TLR2, TLR4, MyD88, and NF-κB in CPB rats. However, the above effects of AMSC-derived exosomes on CPB rats were abolished partially by toll-like receptor 2/4 (TLR2/TLR4) agonist (LPS-EB). In conclusion, AMSC-derived exosomes can improve cognitive function in CPB rats through inhibiting the TLR2/TLR4 signaling pathway.

Low-dose Sevoflurane Attenuates Cardiopulmonary Bypass (CPB)- induced Postoperative Cognitive Dysfunction (POCD) by Regulating Hippocampus Apoptosis via PI3K/AKT Pathway

2020 ◽  
Vol 17 (3) ◽  
pp. 232-240
Author(s):  
Jianhua Qin ◽  
Qingjun Ma ◽  
Dongmei Ma
Keyword(s):  
Cardiopulmonary Bypass ◽  
Cognitive Dysfunction ◽  
Low Dose ◽  
Postoperative Cognitive Dysfunction ◽  
Signal Pathway ◽  
Male Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Akt Inhibitor

Background: Cardiopulmonary bypass (CPB) caused postoperative cognitive dysfunction (POCD) was characterized by hippocampus apoptosis, which seriously limited the therapeutic efficacy and utilization of CPB in clinic. Recent data indicated that sevoflurane anesthesia might alleviate CPB-induced POCD, however, the underlying mechanisms are still unclear. Methods: In the present study, the in vivo CPB-POCD models were established by using aged Sprague-Dawley (SD) male rats and the in vitro hypoxia/reoxygenation (H/R) models were inducted by using the primary hippocampus neuron (PHN) cells. Results: The results showed that CPB impaired cognitive functions and induced hippocampus apoptosis in rat models, which were alleviated by pre-treating rats with low-dose sevoflurane. In addition, the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signal pathway was inactivated in the hippocampus tissues of CPB-POCD rats, which were rescued by low-dose sevoflurane treatment. Of note, the PI3K/AKT inhibitor (LY294002) abrogated the protective effects of low-dose sevoflurane on CPB-POCD rats. Consistently, the in vitro results showed that H/R treatment induced cell apoptosis and inhibited cell viability in PHN cells, which were attenuated by low-dose sevoflurane. Similarly, LY294002 abrogated the inhibiting effects of low-dose sevoflurane on H/R-induced PHN cell death. Conclusion: Taken together, low-dose sevoflurane attenuated CPB-induced POCD by inhibiting hippocampus apoptosis through activating PI3K/AKT signal pathway.

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