scholarly journals Effects of TLR3 and TLR9 Signaling Pathway on Brain Protection in Rats Undergoing Sevoflurane Pretreatment during Cardiopulmonary Bypass

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Zhou Nan ◽  
Zhou Jin ◽  
Cao Huijuan ◽  
Zhang Tiezheng ◽  
Chen Keyan
Keyword(s):  
Brain Injury ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Sham Group ◽  
Brain Protection ◽  
Rat Models ◽  
Tlr9 Expression ◽  
Sd Rats ◽  
Tlr3 Expression ◽  
Tlr9 Signaling

Objective. To investigate the effects of TLR3 and TLR9 signaling pathway on brain injury during CPB in rats pretreated with sevoflurane and its possible molecular mechanism. Methods. SD rats were randomly assigned to sham group, CPB group, and Sev group. Brain tissue was obtained at before CPB (T0), at CPB for 30 minutes (T1), 1 hour after CPB (T3), and 3 hours after CPB (T5). ELISA was used to measure S100-β and IL-6. Western blot was utilized to determine TLR3 and TLR9 expression. TUNEL was applied to detect neuronal apoptosis. Results. Compared with CPB group, at T1, at termination after 1 hour of CPB (T2), T3, 2 hours after CPB (T4) and T5, S100-β and IL-6 decreased in Sev group. Compared with CPB group, IFN-β were increased in Sev group, except T0. Compared with CPB group, TLR3 expression increased, and TLR9 and NF-κB decreased in Sev group. The apoptotic neurons were less in Sev group than in CPB group (P<0.05). Conclusion. Sevoflurane intervention can activate TLR3 and TLR9 signaling pathway, upregulate TLR3 expression and downstream TRIF expression, decrease TLR9 expression, and downregulate downstream NF-κB expression in CPB rat models, thereby mitigating brain injury induced by inflammatory response during CPB.

scholarly journals Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wang Nan ◽  
Xu Zhonghang ◽  
Chen Keyan ◽  
Liu Tongtong ◽  
Guo Wanshu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Protective Effect ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Artery Occlusion ◽  
Rat Models ◽  
Cerebral Artery Occlusion

Background/Aims. Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. Methods. Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. Results. EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. Conclusion. EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway.

Abstract P225: Non-invasive Measurement of Renal Blood Flow (RBF) in Different Rat Models by Magnetic Resonance Imaging (MRI)

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Cesar A Romero ◽  
Robert Knight ◽  
Glauber Cabral ◽  
Oscar A Carretero
Keyword(s):  
Blood Flow ◽  
Sham Group ◽  
Motion Artifacts ◽  
Arterial Stenosis ◽  
7 Tesla ◽  
Hypertensive Rats ◽  
Rat Models ◽  
Non Invasive ◽  
Sd Rats ◽  
Invasive Method

Quantitative measure of RBF provides important information regarding renal physiology and pathology, in different animal’s models. Arterial Spin Labelling-MRI (ASL-MRI) is a non-invasive method to measure blood flow without exogenous contrast media, using arterial water protons labeled by radiofrequency as an endogenous tracer. However, the low signal/noise radio, and the motion artifacts are a challenge for the acquisition of RBF in small animals. Our objective is evaluated the feasibility and reproducibility of the RBF measure by ASL-MRI in different hypertensive rats models. ASL-MRI images were obtained in Sprague-Dawley (SD) rats (200-300g) under inhalation anesthesia using a 7 Tesla Varian MRI system with a spin echo imaging sequence. After 4 days the MRI studies was repeated to evaluate reproducibility, using paired sample T-test and the test-retest reliability (TR) equation. RBF was also measured in in Dahl SS rats on regular chow and spontaneous hypertensive rats (SHR). Additionally we measure the RBF in a set of animals under unilateral nephrectomy (UNx) and renal arterial stenosis (RS) before and after the surgery. Table 1 shows the mean cortical RBF in different rat strains and models. Re-test analysis showed no relevant differences, being the means of differences 9.4±35 ml/min/100g tissue (p=0.58) in SD rats. The TR was 92.4±6%. UNx increase the RBF in 69.1% in comparison with sham group. (p<0.01). After the RS the blood pressure increased and the RBF decrease 56% (p<0.01) in comparison with sham group. ASL-MRI performed with navigator correction and respiratory gating is a feasible and reproducible non-invasive method to measure RBF in several rat models.

scholarly journals TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

scholarly journals MicroRNA-1297 suppressed the Akt/GSK3β signaling pathway and stimulated neural apoptosis in an in vivo sevoflurane exposure model

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052098210
Author(s):  
Quan Wang ◽  
Jingcong Luo ◽  
Ruiqiang Sun ◽  
Jia Liu
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
In Vitro Model ◽  
Nervous System Development ◽  
Exposure Model ◽  
Control Group ◽  
Pten Protein ◽  
Vitro Model

Objective Common inhalation anesthetics used for clinical anesthesia (such as sevoflurane) may induce nerve cell apoptosis during central nervous system development. Furthermore, anesthetics can produce cognitive impairments, such as learning and memory impairments, that continue into adulthood. However, the precise mechanism remains largely undefined. We aimed to determine the function of microRNA-1297 (miR-1297) in sevoflurane-induced neurotoxicity. Methods Reverse transcription-polymerase chain reaction assays were used to analyze miR-1297 expression in sevoflurane-exposed mice. MTT and lactate dehydrogenase (LDH) assays were used to measure cell growth, and neuronal apoptosis was analyzed using flow cytometry. Western blot analyses were used to measure PTEN, PI3K, Akt, and GSK3β protein expression. Results In sevoflurane-exposed mice, miR-1297 expression was up-regulated compared with the control group. MiR-1297 up-regulation led to neuronal apoptosis, inhibition of cell proliferation, and increased LDH activity in the in vitro model of sevoflurane exposure. MiR-1297 up-regulation also suppressed the Akt/GSK3β signaling pathway and induced PTEN protein expression in the in vitro model. PTEN inhibition (VO-Ohpic trihydrate) reduced PTEN protein expression and decreased the effects of miR-1297 down-regulation on neuronal apoptosis in the in vitro model. Conclusion Collectively, the results indicated that miR-1297 stimulates sevoflurane-induced neurotoxicity via the Akt/GSK3β signaling pathway by regulating PTEN expression.

FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

2021 ◽  
pp. 1-9
Author(s):  
Qinhan Hou ◽  
Hongmou Chen ◽  
Quan Liu ◽  
Xianlei Yan
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Water Content ◽  
Neurological Deficit ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Intraventricular Injection ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1β/6, tumor necrosis factor α, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-κB (p-NF-κB), suggesting the inactivation of the TLR4/MyD88/NF-κB pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-κB pathway, providing a potential therapeutic strategy for brain injury in the future.

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