Neuroprotective Effect of Nano Emulsion Containing Salvia on CA1 Region of Hippocampus Following Transient Global Ischemia/Reperfusion in Rat

2021 ◽  
Vol 11 ◽  
Author(s):  
Mahsa Abdolrahimkhan ◽  
Negar Motakef Kazemi ◽  
Shabnam Movassaghi ◽  
Nazanin Gharehkhani ◽  
Hamid Zaferani Arani ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Salvia Officinalis ◽  
Nissl Staining ◽  
Ca1 Region ◽  
Expression Of Genes ◽  
Causes Of Mortality ◽  
Salvia Officinalis L ◽  
Nano Emulsion

Background: Ischemia/reperfusion (I/R) injury is one of the major causes of mortality. I/R injury leads to apoptosis in the brain, especially in the hippocampus and induces cognitive impairments. On the other hand, Salvia officinalis L. is perennial, evergreen subshrub that is widely used in traditional medicine. The antiapoptosis and antioxidant effects of Salvia officinalis L. have also been reported. Objective: In this study, we aimed to investigate the effect of Salvia officinalis L. on the expression of genes involved in apoptosis and percentage of viable neurons in the CA1 hippocampal region of rats following transient global I/R. Methods: The expression of Bcl-2, Bax, and Caspase 3 was evaluated using Real time PCR. Nissl staining was used to measure the number of viable neurons. The percentage of cell viability was also evaluated using MTT assay and flow cytometry. Salvia officinalis L. was injected intraperitoneal at the doses of 50, 75, and 100 mg/kg at both aqueous-alcoholic and aqueous extracts. Results : The expression of Bax and Caspase 3 was increased and the expression of Bcl-2 was decreased following transient global I/R in the CA1 region. The injection of Salvia officinalis L. at most doses reversed the effect of transient global I/R on genes expression. The number of viable neurons in the CA1 region was also decreased following transient global I/R and injection of Salvia officinalis L. at all doses reversed this effect. Conclusion: Transient global I/R significantly promotes apoptosis and cell death, and Salvia officinalis L. may induce neuroprotective and anti-apoptosis effects.

scholarly journals Calreticulin Binds to Fas Ligand and Inhibits Neuronal Cell Apoptosis Induced by Ischemia-Reperfusion Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Beilei Chen ◽  
Zhengzheng Wu ◽  
Jun Xu ◽  
Yun Xu
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Caspase 8

Background. Calreticulin (CRT) can bind to Fas ligand (FasL) and inhibit Fas/FasL-mediated apoptosis of Jurkat T cells. However, its effect on neuronal cell apoptosis has not been investigated.Purpose. We aimed to evaluate the neuroprotective effect of CRT following ischemia-reperfusion injury (IRI).Methods. Mice underwent middle cerebral artery occlusion (MCAO) and SH-SY5Y cells subjected to oxygen glucose deprivation (OGD) were used as models for IRI. The CRT protein level was detected by Western blotting, and mRNA expression of CRT, caspase-3, and caspase-8 was measured by real-time PCR. Immunofluorescence was used to assess the localization of CRT and FasL. The interaction of CRT with FasL was verified by coimmunoprecipitation. SH-SY5Y cell viability was determined by MTT assay, and cell apoptosis was assessed by flow cytometry. The measurement of caspase-8 and caspase-3 activity was carried out using caspase activity assay kits.Results. After IRI, CRT was upregulated on the neuron surface and bound to FasL, leading to increased viability of OGD-exposed SH-SY5Y cells and decreased activity of caspase-8 and caspase-3.Conclusions. This study for the first time revealed that increased CRT inhibited Fas/FasL-mediated neuronal cell apoptosis during the early stage of ischemic stroke, suggesting it to be a potential protector activated soon after IRI.

scholarly journals Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanhua Qin ◽  
Weiming Hu ◽  
Yang Yang ◽  
Zhiying Hu ◽  
Weiyun Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Tunel Staining ◽  
Cox 2

Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5′-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism. Sprague-Dawley rats were divided into five groups. Experimental groups were subjected to 1.5 h transient MCAO. T2-weighted imaging was performed to evaluate brain edema lesions in the stroke rats. Infarct volume was estimated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24 h reperfusion. Western blotting and immunohistochemistry were performed to detect iNOS, caspase-3, Bcl-2, COX-2, and TNF-α protein expressions. Apoptosis was determined by TUNEL staining. T2 hyperintensity changes were observed in primary ischemic region. DAHP pretreatment significantly suppressed iNOS overexpression, caspase-3, and TNF-α. There was also attenuation of neuronal apoptosis with decrement in proteins Bcl-2 and COX-2 expressions. On the basis of our results, we hypothesize DAHP to have a neuroprotective function against focal cerebral ischemia and might attenuate brain injury by decreasing reactive oxygen species (ROS) production, subsequently inhibiting apoptosis.

scholarly journals The Neuroprotective Effect of Atorvastatin on Apoptosis of Hippocampus Following Transient Global Ischemia/ Reperfusion

2016 ◽  
Vol 5 (2) ◽  
pp. 82-89
Author(s):  
Masoumeh Faghani ◽  
Farhang Ejlali ◽  
Zahra Nadia Sharifi ◽  
Hassan Molladoost ◽  
Shabnam Movassaghi
Keyword(s):  
Treatment Group ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Pyramidal Cells ◽  
Male Rats ◽  
Intact Cells ◽  
Ischemic Reperfusion ◽  
Ca1 Region ◽  
Significant Difference ◽  
Ca1 Cells

Background: Hippocampus CA1 cells are highly sensitive to ischemia. Because of anti-oxida­tive property, atorvastatin by eliminating free radicals and other constituent due to cell lesions prevents damages or death of intact cells. The aim of this study is to determine neuroprotective effect of atorvastatin on apoptosis of hippocampus CA1 cells in male rats. Material and Meth­ods: In an experimental study 24 male rats –Wistar adult race- were divided into four groups: Ischemic, vehicle, treatment and control. In order to make an ischemic- reperfusion model, common carotid artery was clamped bilaterally for 20 minutes. In treatment group, the first dose of Atorvastatin (10mg/kg) was injected six hours after ischemic- reperfusion and 24, 48 and 72 later intraperitoneally. Four days after ischemic- reperfusion tissue section were obtained and stained using Nissl method. Then intact healthy pyramidal CA1 hippocampus cells were counted. TUKEY and One Way ANOVA were used for analyzing the obtained results. Results: No significant difference was found in numbers of healthy intake pyramidal and apoptotic cells of CA1 hippocampus region between treatment group (10mg/kg Atorvastatin) and controls, whereas a significant reduction of these cells was observed in ischemia and vehicle groups in comparison to controls (P<0.05). Conclusion: Using 10mg/kg atorvastatin following cerebral ischemia- reperfusion has a protective effect on pyramidal cells of CA1 region in hippocampus in male rats leading to reduction of degeneration and apoptosis.[GMJ.2016;5(2):82-89]

scholarly journals Neuroprotective Effect of Sodium Butyrate against Cerebral Ischemia/Reperfusion Injury in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Sun ◽  
Fangyan Wang ◽  
Haixiao Li ◽  
Huiqing Zhang ◽  
Jiangtao Jin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Sodium Butyrate ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Morphological Examination ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Sodium butyrate (NaB) is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R) injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg) was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO) mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt), and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.

scholarly journals Shenxiong Drop Pill exerts neuroprotective effect against focal cerebral ischemia partly via regulation of the expressions of ICAM-1 and caspase-3

2021 ◽  
Vol 20 (10) ◽  
pp. 2015-2022
Author(s):  
Shuo-guo Jin ◽  
Ze-ran Chen ◽  
Yang Zhang ◽  
Meng-yuan Huang ◽  
Meng Hou ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Caspase 3 ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Triphenyltetrazolium Chloride ◽  
Scoring Method ◽  
Nissl Staining ◽  
Neuroprotective Effects

Purpose: To investigate the effect of Shenxiong Drop Pill (SXDP) on cerebral infarction (CI) in rats, and the involvement of anti-inflammatory response in the process.Methods: Rats were sacrificed at three different time points, viz, 24, 48 and 72 h after establishment of CI model. Neurological deficit score (NDS) was determined using Bederson’s neurological behavioral scoring method, whereas triphenyltetrazolium chloride (TTC) staining was used to show brain injury. The integrated optical density (IOD) of Nissl bodies and caspase-3-positive nerve cells were measured with Nissl staining and SP kit, respectively. The mRNA expression of intercellular adhesion molecule 1(ICAM-1) was determined using reverse transcription-polymerase chain reaction (RT-PCR).Results: SXDP produced neuroprotective effect at high, medium, and low doses. The infarct volumes in the high-, medium- and low-dose SXDP, and cyclophosphamide groups were significantly reduced at each time point. Different doses of SXDP significantly reduced the mRNA expression of ICAM-1 and the IOD of caspase-3.Conclusion: These results indicate that SXDP exerts neuroprotective effects against ischemic injury by negatively regulating ICAM-1/caspase-3 downstream of inflammatory and apoptosis pathways.

scholarly journals Orexin-A Alleviates Astrocytic Apoptosis and Inflammation via Inhibiting OX1R-mediated NF-κB and MAPK Signaling Pathways in Cerebral Ischemia/reperfusion Injury

2021 ◽  
Author(s):  
Dandan Xu ◽  
Tingting Kong ◽  
Ziqi Shao ◽  
Rumin Zhang ◽  
Shengnan Zhang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Caspase 9 ◽  
Astrocyte Activation ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Pro Inflammatory Cytokines

Abstract Background: Orexin-A (OXA) is a neuropeptide with neuroprotective effect by reducing cerebral ischemia/reperfusion injury (CIRI). Inflammation and apoptosis mediated by astrocyte activation are the key pathological mechanisms for CIRI. We thus attempted to confirm neuroprotective effects of OXA on astrocytic inflammation and apoptosis in CIRI and clarify the relative mechanisms. Methods: A middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and U251 glioma cells model subjected to oxygen glucose deprivation and reperfusion (OGD/R) were established, with or without OXA treatment. Neurological deficit score was determined, and cerebral infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western Blot was used to detect the expressions of NF-κB p65, p-ERK, p-p38, GFAP, OX1R, IL-1β, TNF-α, IL-6, iNOS, Bcl-2, Bax, CytC, cleaved caspase-9 and cleaved caspase-3 in vivo and vitro. Pro-inflammatory cytokines in cell supernatant IL-1β, TNF-α and IL-6 were determined by ELISA. Hoechst 33342 staining was used to detect the apoptosis of astrocyte. Immunofluorescent staining was performed to assess the nuclear translocation of p65 and the expression of GFAP. Results: The results showed that OXA significantly improved neurological deficit score and decreased the volume of infarct area in brain. OXA decreased inflammatory mediators, inhibited astrocyte activation and nuclear translocation of NF-κB and phosphorylation of MAPK/ERK and MAPK/p38. Besides, OXA suppressed apoptosis via upregulating the ratio of Bcl-2/Bax and downregulating cytochrome C, cleaved-caspase-9 and cleaved caspase-3. Conclusions: Overall, it was concluded that OXA exerts neuroprotective effect during CIRI through attenuating astrocytes apoptosis, astrocytes activation and pro-inflammatory cytokines production, by Inhibiting OX1R-mediated NF-κB, MAPK/ERK and MAPK/p38 signaling pathways. The progress in our study are helpful to elucidate the molecular mechanisms of OXA neuroprotection, which could lead to the development of new treatment strategies for ischemic stroke.

scholarly journals Neuroprotective Effect of Moxibustion on Cerebral Ischemia/Reperfusion Injury in Rats by Downregulating NR2B Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhong Di ◽  
Qin Guo ◽  
Quanai Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Western Blot ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurological Dysfunction ◽  
Moxibustion Group ◽  
Cerebral Ischemia Reperfusion ◽  
Group I

Objective. Stroke is a common and frequently occurring disease of the central nervous system, which is characterized by high mortality and a high disability rate. Moxibustion is a common method for treating stroke in traditional Chinese medicine, but its neuroprotective mechanism is unknown. N-Methyl-D-Aspartate Receptor Subunit 2B (NR2B) plays an important role in neuronal apoptosis. The objective of this study was to explore the mechanisms underlying the neuroprotective effect of moxibustion on cerebral ischemia/reperfusion (I/R) injury based on NR2B. Methods. Sprague–Dawley rats were randomly divided into 5 groups: the control group, I/R group, I/R + moxibustion group, I/R + Ro25-6981 (NR2B antagonist) group, and I/R + Ro25-6981 + moxibustion group. The cerebral ischemia/reperfusion model was induced by middle cerebral artery occlusion. Before the establishment of the model, the Ro25-6981 group received intraperitoneal injections of Ro25-6981, the moxibustion group received moxibustion, and the Ro25-6981 + moxibustion group received both interventions. The neurological dysfunction was evaluated by a neurological deficiency score (NDS). The infarct volume was examined by TTC (2,3,5-triphenyltetrazolium chloride) staining. The apoptosis rate of cerebral cells in the ischemic area was examined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining, and the expression of Bcl-2, Bax, and caspase-3 was observed by western blot. NR2B and JNK were also observed by western blot. Results. Compared with the I/R group, moxibustion significantly decreased the neurological deficiency score ( P  < 0.05) and the infarct rate ( P  < 0.01) in I/R rats which were similar to those in the Ro25-6981 group. After moxibustion treatment, there was a significant decrease in the apoptosis rate ( P  < 0.001) and the protein expression levels of Bax, caspase-3, and JNK ( P  < 0.001) and an increase in the expression of Bcl-2 ( P  < 0.01). Compared with the I/R group, moxibustion downregulated the expression of NR2B and decreased the activity of NR2B in the cerebral ischemia area ( P  < 0.001). Conclusions. Moxibustion can improve neurological dysfunction and decrease infarction area and neuronal apoptosis caused by cerebral ischemia/reperfusion in rats. Its neuroprotective mechanism may be related to downregulating the expression of NR2B.

scholarly journals Neuroprotective Effect of Daidzein Extracted From Pueraria lobate Radix in a Stroke Model Via the Akt/mTOR/BDNF Channel

2022 ◽  
Vol 12 ◽  
Author(s):  
Meizhu Zheng ◽  
Mi Zhou ◽  
Minghui Chen ◽  
Yao Lu ◽  
Dongfang Shi ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Experimental Stroke ◽  
Stroke Model ◽  
Mtor Signaling Pathway ◽  
Therapeutic Research

Daidzein is a plant isoflavonoid primarily isolated from Pueraria lobate Radix as the dry root of P. lobata (Wild.) Ohwi, have long been used as nutraceutical and medicinal herb in China. Despite the report that daidzein can prevent neuronal damage and improve outcome in experimental stroke, the mechanisms of this neuroprotective action have been not fully elucidated. The aim of this study was to determine whether the daidzein elicits beneficial actions in a stroke model, namely, cerebral ischemia/reperfusion (I/R) injury, and to reveal the underlying neuroprotective mechanisms associated with the regulation of Akt/mTOR/BDNF signal pathway. The results showed that I/R, daidzein treatment significantly improved neurological deficits, infarct volume, and brain edema at 20 and 30 mg/kg, respectively. Meanwhile, it was found out that the pretreatment with daidzein at 20 and 30 mg/kg evidently improved striatal dopamine and its metabolite levels. In addition, daidzein treatment reduced the cleaved Caspase-3 level but enhanced the phosphorylation of Akt, BAD and mTOR. Moreover, daidzein at 30 mg/kg treatment enhanced the expression of BDNF and CREB significantly. This protective effect of daidzein was ameliorated by inhibiting the PI3K/Akt/mTOR signaling pathway using LY294002. To sum up, our results demonstrated that daidzein could protect animals against ischemic damage through the regulation of the Akt/mTOR/BDNF channel, and the present study may facilitate the therapeutic research of stroke.

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