Effect of Parecoxib on Hippocampus and Hypothalamic Orexin Neurons in Rats with Cerebral Infarction

2021 ◽  
Vol 11 (4) ◽  
pp. 679-683
Author(s):  
Yapeng Guo ◽  
Heng Xu ◽  
Xuyi Li ◽  
Zhiming Zhou
Keyword(s):  
Cerebral Infarction ◽  
Protective Effect ◽  
Infarct Size ◽  
Hippocampal Neurons ◽  
Neuronal Apoptosis ◽  
Low Dose ◽  
Human Life ◽  
Sham Operation ◽  
Sham Operation Group ◽  
Orexin Neuron

Cerebral infarction has seriously threatened human life and health. Parecoxib is the first nonsteroidal analgesic for surgical analgesia. However, its effect on orexin neurons during cerebral infarction treatment is unclear. In this study, a rat model of cerebral infarction was established by suture method. The experiment was assigned into sham operation group, cerebral infarction model group (MCAO), high and low dose group of parecoxib. Western blotting and immunofluorescence staining was used to evaluate the activity of orexin neurons. The infarct size was evaluated by TTC staining. The apoptosis of neurons in hypothalamus and hippocampus was determined by AV-PI staining. TTC staining suggested that parecoxib treatment significantly reduced cerebral infarct size, increased orexin neuronal activity, and decreased neuronal apoptosis in hypothalamus and hippocampus, which were significantly different from sham-operated groups. This study demonstrates that parecoxib has a protective effect on cerebral infarction rats, which can inhibit the apoptosis of hypothalamic and hippocampal neurons through the orexin neuron pathway. It provides a theoretical basis for the protective effect of parecoxib, indicating that it might be a new target for the treatment of cerebral infarction.

scholarly journals N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

2019 ◽  
Vol 242 (2) ◽  
pp. 37-50 ◽  
Author(s):  
Sivaporn Sivasinprasasn ◽  
Siripong Palee ◽  
Kenneth Chattipakorn ◽  
Thidarat Jaiwongkum ◽  
Nattayaporn Apaijai ◽  
...  
Keyword(s):  
Infarct Size ◽  
Mitochondrial Dysfunction ◽  
Low Dose ◽  
Ischemia Reperfusion ◽  
Cardiac Ischemia ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Myocardial Infarct Size ◽  
Ovx Rats ◽  
Cardiometabolic Function

Myocardial damage and mitochondrial dysfunction caused by cardiac ischemia-reperfusion (I/R) injury are intensified by endogenous estrogen deprivation. Although N-acetylcysteine (NAC) exerted cardioprotective effects, its benefits when used in combination with hormone therapy are unknown. We tested the hypothesis that a combination of NAC with low-dose estrogen improves cardiometabolic function and protects cardiac mitochondria against I/R injury, to a similar extent to regular-dose estrogen treatment, in estrogen-deprived rats. Female Wistar rats had a bilateral ovariectomy (OVX) or sham operation. Twelve weeks after the operation, OVX rats were treated with regular-dose estrogen (E; 50 µg/kg/day), low-dose estrogen (e; 25 µg/kg/day), NAC (N; 100 mg/kg/day) or combined low-dose estradiol with NAC (eN) for 4 weeks (n = 6/group). Metabolic parameters, echocardiography, heart rate variability and then cardiac I/R protocol involving 30-min coronary artery ligation, followed by 120-min reperfusion, were performed. OVX rats had increased body weight, visceral fat, fasting plasma glucose, HOMA-IR index, triglycerides, cholesterol and LDL levels (P < 0.05 vs sham). Only OVX-E and OVX-eN had a similarly improved HOMA-IR index. LVEF was increased in all treatment groups, but HRV was restored only by OVX-E and OVX-eN. After I/R, myocardial infarct size was decreased in both OVX-E and OVX-eN groups. OVX-E and OVX-eN rats similarly had a reduced mitochondrial ROS level and increased mitochondrial membrane potential in the ischemic myocardium. In conclusion, combined NAC with low-dose estrogen and regular-dose estrogen therapy similarly improve cardiometabolic function, prevent cardiac mitochondrial dysfunction and reduces the infarct size in estrogen-deprived rats with cardiac I/R injury.

scholarly journals Enriched Environment Regulates Dendritic Cells to Alleviate Inflammation in Cerebral Infarction Lesions

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Zhenzhen Zhong ◽  
Ping Xu ◽  
Jun Wen ◽  
Xiangdong Li ◽  
Xiaobo Zhang
Keyword(s):  
Dendritic Cells ◽  
Cerebral Infarction ◽  
Brain Tissue ◽  
Neuronal Injury ◽  
Enriched Environment ◽  
Sham Operation ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sham Operation Group ◽  
Tnf Α

Objective. The aim was to investigate the role that enriched environment (EE) plays in the regulation of inflammation in cerebral infarction (CI) lesions and further explore the relationship between this regulation and dendritic cells (DCs). Methods. 72 Sprague-Dawley rats were randomly divided into sham operation group (CON group, n = 24 ) and CI model group ( n = 48 ). On completion of the establishment of CI rat models by Longa’s method, rats in the models group were further assigned to standard environment group (NC group, n = 24 ) and EE group ( n = 24 ). HE staining was utilized for evaluation of neuronal injury in the lesions. The number of CD74- and integrin αE-positive cells was detected by immunofluorescence. The expression of the IL-1β, IL-6, and TNF-α in the brain tissue and serum of rats was measured by immunohistochemistry and ELISA, respectively. Results. In comparison with the CON group, the NC and EE groups showed significant increases in neuronal injury, CD74- and Integrin αE-positive cells, DC content, as well as IL-1β, IL-6, and TNF-α expression in brain tissue and serum. According to the further comparison between the NC group and EE group, the latter showed decreases in each indicator, and these decreases were in a time-dependent manner. Conclusion. EE avoids the accumulation of DCs in the lesions and reduces the contents of IL-1β, IL-6, and TNF-α, consequently promoting the recovery of CI. And better recovery results can be obtained through increasing the time to stay in EE.

scholarly journals Nitroglycerine limits infarct size through S-nitrosation of cyclophilin D: a novel mechanism for an old drug

2018 ◽  
Vol 115 (3) ◽  
pp. 625-636 ◽  
Author(s):  
Sofia-Iris Bibli ◽  
Andreas Papapetropoulos ◽  
Efstathios K Iliodromitis ◽  
Andreas Daiber ◽  
Voahanginirina Randriamboavonjy ◽  
...  
Keyword(s):  
Protective Effect ◽  
Infarct Size ◽  
Knockout Mice ◽  
Low Dose ◽  
Myocardial Infarct ◽  
Pharmacological Action ◽  
Myocardial Infarct Size ◽  
Cyclophilin D ◽  
Cardioprotective Effects

Abstract Aims Nitroglycerine (NTG) given prior to an ischaemic insult exerts cardioprotective effects. However, whether administration of an acute low dose of NTG in a clinically relevant manner following an ischaemic episode limits infarct size, has not yet been explored. Methods and results Adult mice were subjected to acute myocardial infarction in vivo and then treated with vehicle or low-dose NTG prior to reperfusion. This treatment regimen minimized myocardial infarct size without affecting haemodynamic parameters but the protective effect was absent in mice rendered tolerant to the drug. Mechanistically, NTG was shown to nitrosate and inhibit cyclophilin D (CypD), and NTG administration failed to limit infarct size in CypD knockout mice. Additional experiments revealed lack of the NTG protective effect following genetic (knockout mice) or pharmacological inhibition (L-NAME treatment) of the endothelial nitric oxide synthase (eNOS). The protective effect of NTG was attributed to preservation of the eNOS dimer. Moreover, NTG retained its cardioprotective effects in a model of endothelial dysfunction (ApoE knockout) by preserving CypD nitrosation. Human ischaemic heart biopsies revealed reduced eNOS activity and exhibited reduced CypD nitrosation. Conclusion Low-dose NTG given prior to reperfusion reduces myocardial infarct size by preserving eNOS function, and the subsequent eNOS-dependent S-nitrosation of CypD, inhibiting cardiomyocyte necrosis. This novel pharmacological action of NTG warrants confirmation in clinical studies, although our data in human biopsies provide promising preliminary results.

scholarly journals Electroacupuncture Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulation of Autophagy and Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shi Shu ◽  
Chun-Ming Li ◽  
Yan-Li You ◽  
Xiao-Lu Qian ◽  
Shuang Zhou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Neurological Deficit ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beclin 1 ◽  
Male Rats ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sham Operation Group

Background. The therapeutic mechanisms of cerebral ischemia treatment by acupuncture are yet not well addressed.Objective. We investigated the effects of electroacupuncture (EA) at GV26 observing the expression of autophagy-related proteins Beclin-1 and LC3B and proportion of apoptotic cells and Bcl-2 positive cells in MCAO/R model rats.Methods. Sprague-Dawley (SD) male rats were randomly assigned to 7 groups: model groups (M6h, M24h, and M72h), EA treatment groups (T6h, T24h, and T72h), and sham operation group (S). Neurological deficit and cerebral infarction volume were measured to assess the improvement effect, while the expression of Beclin-1 and LC3B and proportion of Tunel-positive and Bcl-2 positive cells were examined to explore EA effect on autophagy and apoptosis.Results. EA significantly decreased neurological deficit scores and the volume of cerebral infarction. Beclin-1 was significantly decreased in T24h, while LC3B-II/LC3B-I ratio markedly reduced in 6th hour. EA groups markedly reduced the number of Tunel positive cells, especially in T24h. Meanwhile, the number of Bcl-2 positive cells obviously increased after EA treatment, especially in T6h and T24h.Conclusions. The alleviation of inadequate autophagy and apoptosis may be a key mechanism involved in the reflex regulation of EA at GV26 to treat cerebral ischemia.

Effect of Ultramicro Superparamagnetic Iron Oxide Nanoparticles on Cerebral Infarction in Mice

2020 ◽  
Vol 20 (12) ◽  
pp. 7305-7310
Author(s):  
Bin Zhang ◽  
Xiuting Di ◽  
Yizhou Song ◽  
Banglin Li
Keyword(s):  
Inflammatory Response ◽  
Cerebral Infarction ◽  
Normal Saline ◽  
Saline Control ◽  
Control Group ◽  
Sham Operation ◽  
Saline Control Group ◽  
Sham Operation Group ◽  
Infarction Volume ◽  
Operation Group

To investigate the effect of Feraheme (ferumoxytol) intravenous injection on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion. We randomly divided 30 CS7BL6J mice into sham operated group, normal saline control group, and Feraheme group with 10 mice in each group. The model of permanent occlusion of right middle cerebral artery was made via the modified suture method in the normal saline control group and the Feraheme group. After 24 h of establishment the model, the tail vein was injected with 18 mg/kg Feraheme in the sham operation group and Feraheme group, and the normal saline control group was injected with an equal volume of normal saline. Neurobehavioral scores were obtained 24 h (before injection of Feraheme or normal saline) and 48 h (before MRI) after the model was established. The volume of cerebral infarction was calculated according to T2 weighted imaging. Orbital blood was collected after nodal scanning to detect serum TNF-α, IL-1β, and IL-6 levels. Then, the brain tissues of mice were killed for HE staining and IBAL immunohistochemical staining. No significant differences in cerebral infarction volume and neurological function were observed between the normal saline control group and Feraheme group. The levels of TNF-α, IL-1β and IL-6 in the normal saline control group and Feraheme group were significantly higher than those in the sham operation group (P < 0.05), but there were no significant differences between the normal saline control group and Feraheme group. We showed that intravenous injection of 18 mg/kg Feraheme 24 h after cerebral ischemia does not affect the infarct volume and inflammatory response, suggesting that the dose of Feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

scholarly journals The protective effect of celery (Apium graveolens L.) ethanol extract on anemia in 5/6 subtotal nephrectomy rat model

2020 ◽  
Vol 39 (1) ◽  
pp. 12
Author(s):  
Afifah Afifah ◽  
Khusnul Muflikhah ◽  
Tri Lestari ◽  
Eman Sutrisna ◽  
Ajeng Kirana ◽  
...  
Keyword(s):  
Protective Effect ◽  
Rat Model ◽  
Hematological Parameters ◽  
Ethanol Extract ◽  
Study Data ◽  
Apium Graveolens ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sham Operation Group ◽  
Subtotal Nephrectomy

Background<br />Anemia is a frequent complication of chronic kidney disease (CKD). Anemia in CKD is associated with reduced quality of life, increased cardiovascular disease, cognitive impairment, and mortality. Therefore it is necessary to find an alternative agent for preventing anemia in CKD. Celery is one of the natural substances that have anti-inflammatory, antioxidant, and antihypertensive pharmacological effects. Based on the mechanism of CKD and its progression, celery is thought to prevent anemia in CKD. This research was aimed at evaluating the protective effect of celery extract against anemia in a CKD rat model. <br /><br />Methods<br />This was an experimental laboratory study using 25 male Sprague Dawley rats, aged 2-3 months, they were randomized into 5 groups, namely group A, sham operation; group B, subtotal nephrectomy; group C, D, E, subtotal nephrectomy + 250, 500, 1000 mg/kg BW ethanol extract of celery, respectively. The administration of celery extract was performed 14 days before and 14 days after induction of 5/6 subtotal nephrectomy. The hematological parameters (Hb, RBC, Ht, MCV, MCH, MCHC) and serum creatinine level were measured at the end of the study. Data were analyzed with One Way ANOVA and Kruskal-Wallis test followed by Mann-Whitney test at p&lt;0.05. <br /><br />Results<br />There were no significant differences between groups in Hb, RBC, Ht, MCV (p&gt;0.05) and significant differences between groups in MCH and MCHC (p&lt;0.05). The highest levels of Hb, RBC, and Ht were found in group C.<br /><br />Conclusion<br />Celery ethanol extract at a dose of 250 mg/kg BW/day may prevent anemia in the CKD rat model.

scholarly journals Protective Effect of Low-Dose Alcohol Consumption against Post-Ischemic Neuronal Apoptosis: Role of L-PGDS

2021 ◽  
Vol 23 (1) ◽  
pp. 133
Author(s):  
Chun Li ◽  
Jiyu Li ◽  
Ethyn G. Loreno ◽  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Alcohol Consumption ◽  
Protective Effect ◽  
Neuronal Apoptosis ◽  
Low Dose ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Prostaglandin D2 ◽  
Permanent Disability ◽  
Cerebral Ischemia Reperfusion

Ischemic stroke is one of the leading causes of permanent disability and death in adults worldwide. Apoptosis is a major element contributing to post-ischemic neuronal death. We previously found that low-dose alcohol consumption (LAC) protects against neuronal apoptosis in the peri-infarct cortex following transient focal cerebral ischemia. Lipocalin-type prostaglandin D2 synthase (L-PGDS), which is mainly localized in the central nervous system (CNS), was previously shown to inhibit neuronal apoptosis. Therefore, we determined whether L-PGDS is involved in the protective effect of LAC against post-ischemic neuronal apoptosis. Wild-type (WT), CaMKIIαCreERT2/+/L-PGDS+/+, and CaMKIIαCreERT2/+/L-PGDSflox/flox mice on a C57BL/6J background were gavage fed with ethanol or volume-matched water once a day for 8 weeks. Tamoxifen (2 mg/day) was given intraperitoneally to CaMKIIαCreERT2/+/L-PGDS+/+ and CaMKIIαCreERT2/+/L-PGDSflox/flox mice for 5 days during the fourth week. AT-56 (30 mg/kg/day), a selective inhibitor of L-PGDS, was given orally to AT-56-treated WT mice from the fifth week for four weeks. Cerebral ischemia/reperfusion (I/R) injury, TUNEL-positive neurons, and cleaved caspase-3-positive neurons were measured at 24 h of reperfusion after a 90 min unilateral middle cerebral artery occlusion (MCAO). We found that 0.7 g/kg/day but not 2.8 g/kg/day ethanol significantly upregulated L-PGDS in the cerebral cortex. In addition, 0.7 g/kg/day ethanol diminished cerebral ischemia/reperfusion (I/R) injury and TUNEL-positive and cleaved caspase-3-positive neurons in the peri-infarct cortex in WT and CaMKIIαCreERT2/+/L-PGDS+/+ mice. Furthermore, the neuroprotective effect of 0.7 g/kg/day ethanol was alleviated in AT-56-treated WT and CaMKIIαCreERT2/+/L-PGDSflox/flox mice. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing post-ischemic neuronal apoptosis via an upregulated L-PGDS.

Effects of Bone Marrow Mesenchymal Stem Cells on Neurological Function, Transforming Growth Factor Beta 1 and Nogo-A Expression in Stroke Rats

2021 ◽  
Vol 11 (12) ◽  
pp. 2466-2471
Author(s):  
Kang Hu ◽  
Gaojie Qu
Keyword(s):  
Cerebral Infarction ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Infarct Volume ◽  
Neurological Function ◽  
Sham Operation ◽  
Sham Operation Group ◽  
Ischemic Group ◽  
Ischemia Group ◽  
Operation Group

To investigate BMSCs’ effect on neurological function, TGF-β1 and Nogo-A expression in stroke rats. Rats were assigned into sham operation group, ischemia group (MACO rat model) and BMSCs group (BMSCs transplantation) followed by analysis of neurological function, brain pathological changes, cerebral infarction volume, TGF-β1 and Nogo-A level by Western blot. Compared with sham operation group, the score of rats was significantly elevated in ischemic group and decreased in BMSCs group (P <0.05). Compared with sham-operated group, ischemic group showed significantly increased cerebral infarction area (P <0.05) and BMSCs group had a significant decreased water level and brain infarct volume (P < 0.05). Compared with sham-operated group, ischemic group had more edema in the nerve cells with serious vacuole, uneven cytoplasm staining and reduced number of neurons, which were all significantly improved in BMSCs group. Compared to sham group, ischemic group showed significantly reduced TGF-β1 and increased Nogo-A level (P <0.05), which were all reversed in BMSCs group (P <0.05). BMSCs transplantation can significantly improve the nerve function of stroke rats, promote TGF-β1 secretion and inhibit Nogo-A expression.

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