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

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.

2022 ◽  
Vol 32 (1) ◽  
Author(s):  
Chengren Gou ◽  
Tong Liu ◽  
Zongping Chen ◽  
Zidong Zhou ◽  
Tao Song ◽  
...  

Abstract Background The ischiocavernosus muscle (ICM) encompasses a pair of short pinnate muscles attached to the pelvic ring. The ICM begins at the ischial tuberosity and ends at the crus of the penis while covering the surface of the crus. According to the traditional view, the contraction of the ICM plays an auxiliary role in penile erection. However, we have previously shown that the ICM plays an important role in penile erection through an indirect method of diagnosing erectile dysfunction (ED) caused by ICM injury by observing the infertility of paired female rats. Since intracavernosal pressure (ICP) is the current gold standard for diagnosing ED, this study aimed to amputate unilaterally/bilaterally the ICM to establish an ED model by detecting the ICP, recording the infertility of matching female rats, and comparing the two methods. Results Forty sexually mature adult male rats were selected and randomly divided into the following groups: the control group (n = 10), sham operation group (n = 10), unilateral ischiocavernosus muscle (Uni-ICM) amputation group (n = 10), and bilateral ischiocavernosus muscle (Bi-ICM) amputation group (n = 10). Eighty female reproductive rats were randomly assigned to the above groups at a ratio of 2:1. We evaluated the time to conception for the paired female rats and the effects of unilateral/bilateral severing of the ICM on erectile function. The results showed that the baseline and maximum intracavernosal pressure (ICP) in the control group, sham operation group, Uni-ICM amputation group, and Bi-ICM amputation group were 17.44±2.50 mmHg and 93.51±10.78 mmHg, 17.81±2.81 mmHg and 95.07±10.40 mmHg, 16.73±2.11 mmHg and 83.49±12.38 mmHg, and 14.78±2.78 mmHg and 33.57±6.72 mmHg, respectively, immediately postsurgery. The max ICP in the Bi-ICM amputation group was lower than that in the remaining three groups (all P<0.05). The pregnancy rates were 100, 100, 90, and 0% in the control group, sham operation group, Uni-ICM amputation group, and the Bi-ICM amputation group, respectively. The pregnancy rate in the Bi-ICM amputation group was significantly lower than that in the remaining groups (all P<0.05). The time to conception was approximately 7–10 days later in the Uni-ICM amputation group than in the control and sham groups (all P<0.05). Conclusions Male rats undergoing Bi-ICM amputation may develop permanent ED, which affects their fertility. In contrast, rats undergoing Uni-ICM amputation may experience transient ED.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Zhao Jing ◽  
Yan Yi ◽  
Huang Xi ◽  
Lun-Quan Sun ◽  
Li Yanping

Objective. Bone mesenchymal stem cells (BMSCs) transplantation has a therapeutic effect on the thin endometrium in animal researches and clinical trials. The present study aims at assessing whether transplantation of VEGF-transfected BMSCs (VEGF-BMSCs) have a better therapeutic effect on endometrial regeneration and endometrial receptivity compared with BMSCs therapy alone. Methods. Sprague-Dawley (SD) rats were used in the study. Thin endometrium model was established with 95% ethanol injection into uterine. VEGF-BMSCs or BMSCs was transplanted via tail vein IV injection. Endometrial thickness, morphology, and pinopodes were assessed by hematoxylin and eosin (HE) staining and scanning electron microscope (SEM). The proteins and mRNAs expressions of markers for endometrial cells and endometrial receptivity were measured after treatment. The fertility testing was done to assess the embryo implantation efficiency. Results. VEGF-BMSCs transplantation significantly increased endometrial thickness compared with the BMSCs group and the control group. There was no significant difference in endometrial thickness between VEGF-BMSCs group and sham operation group. Importantly, in protein level, expressions of cytokeratin, vitamin, VEGF, LIF, and integrin ανβ3 in VEGF-BMSC group were increased dramatically compared with those of the control group and BMSC group both 4 days and 8 days after stem cells transplantation. Accordingly, mRNA expression of LIF and integrin ανβ3 was significantly upregulated compared with those of the control group and BMSC group both 4 and 8 days after treatment. The pinopodes were developed better in the VEGF-BMSCs group and the sham operation group compared with BMSCs group and the control group. The number of embryo implantation is largest in the sham operation group, followed by VEGF-BMSCs group, BMSCs group, and the control group. Conclusions. Transplantation of VEGF gene-transfected BMSCs may be a better therapeutic treatment for thin endometrium than stem cell therapy alone.


Author(s):  
Na Yuan ◽  
Xiuzhen Wang ◽  
Yu Zhang ◽  
Lingsi Kong ◽  
Liyong Yuan ◽  
...  

Background: The Postoperative cognitive dysfunction (POCD) model was constructed by resection of the left hepatic lobe in aged mice to determine the behavioral effects of the POCD model in aged mice and the relationship between NF-κB and POCD in apoptosis and autophagy. Provide a theoretical basis for POCD prevention and treatment. Methods: This study was carried out in Ningbo No. 6 Hospital, Zhejiang, China, from Jun 2019 to Dec 2020. The POCD model was constructed after resection of the left extrahepatic lobe in aged mice and randomly divided into 6 groups: sham operation group, operation group (normal saline control group, solvent group, YC-1 group, PDTC group and 3-MA group). Related indicators of behavioral changes, neuronal inflammatory responses, apoptosis, and autophagy were examined. Results: The escape latency of the aged mice in the surgical group was significantly prolonged at three time points compared with the control group, and the number of insertions decreased significantly. Microglia are activated and the inflammatory response is increased, whereas PDTC has an inhibitory effect. It was demonstrated that apoptosis and necrosis of neurons can be induced by the NF-κb pathway, and autophagy can be promoted, whereas autophagy occurs before apoptosis. Conclusion: Activation of NF-κb pathway in neurons after POCD causes neuronal apoptosis and autophagy, and cognitive impairment occurs. PDTC, a NF-κb pathway inhibitor, can effectively reduce neuronal apoptosis induced by secondary brain injury after POCD. Necrosis, to protect the brain tissue.  


2019 ◽  
Vol 9 (6) ◽  
pp. 860-864
Author(s):  
Yu Zeng ◽  
Hongyu Duan ◽  
Yujiang Peng ◽  
Bo Shao ◽  
Xijun He ◽  
...  

This study is to investigate the expression of serum S100A8/A9 in rats after cardiopulmonary resuscitation (CPR) and its correlation with brain injury after CPR. Thirty-six male SD rats were randomly divided into control group (n = 6), cardiopulmonary resuscitation group (n = 24) and sham operation group (n = 6). The cardiopulmonary resuscitation group was further divided into four subgroups according to the time after recovery of autonomous circulation: 6-hour group, 12-hour group, 24-hour group and 48-hour group, with 6 rats in each group. The rats in the cardiopulmonary resuscitation group was conducted by asphyxia then given cardiopulmonary resuscitation (CPR), while the rats in the sham operation group were given tracheal intubation without asphyxia. The rats in each group were assessed by modified Neurological Severity Score (mNSS). The vein blood from tail was collected to detect the expression of serum S100A8/A9. Then the brain tissue was taken to measure the water content. Our results showed that the neurological function of the sham-operated group and the control group was normal, the mNSS scores of which were 0. However, the neurological function score in the CPR group decreased gradually with time, but it was still significantly higher than that in the normal value until 48 hours (P < 0.05). There was no significant difference in brain water content between the sham-operated group and the control group (P > 0.05). The water content of brain tissue in sham-operated group was higher than that in control group at 6 h, and the amount was increasing as the time extended. The level reached the highest at 24 h and started to decrease at 48 h, but the it was still higher than that in sham-operated group (P < 0.05). The expression level of serum S100 A8/A9 in sham-operated group was slightly higher than that in control group, but there was no statistical difference (P > 0.05); The expression level of S100 A8/A9 in cardiopulmonary resuscitation group was significantly higher than that in control group at 6 h, and still increased at 24 h. Although the level decreased at 48 h, but was still higher than that in sham operation group (P < 0.05). The mNSS score and brain water content were significantly positively correlated with serum S100 A8/A9 (r = 0.48, P < 0.001; r = 0.63, P < 0.001). In conclusion, the level of serum S100A8/A9 in rats after cardiopulmonary resuscitation is significantly increased, which is positively correlated with the degree of brain injury in rats.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng-yu Zhang ◽  
Jie-ping Wang ◽  
Kai He ◽  
Xian-ming Xia

AbstractDevelop a rat model of hilar cholangiocarcinoma for detecting bile salt export pump (Bsep) expression in hilar cholangiocarcinoma tissues, in order to provide a new therapeutic target for the gene therapy of hilar cholangiocarcinoma. Sixty male Wistar rats (body weight, 190 ± 8 g) were randomly divided into three groups (the experimental group, the control group and the sham operation group, n = 20 each) as follows: The three groups were fed a standard diet, the experimental group was injected by cholangiocarcinoma QBC939 cell suspension along the hilar bile duct into the bile duct bifurcation with microsyringe, the control group was injected by normal saline, the sham operation group did not inject anything. Every day assess the rats’ mental state, diet, and motion by using Basso–Beattie–Bresnahan and combined behavioral score. At 4 weeks, one rat of the experimental group was sacrificed after it was administered anesthesia, and we recorded changes in hilar bile duct size, texture, and form. This procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma developed only in the experimental group, thereby establishing an experimental model for studying QBC939-induced hilar cholangiocarcinoma. Tumor formation was confirmed by pathological examination, and hilar bile duct tissues were harvested from both the groups. A real-time polymerase chain reaction assay and an immunohistochemical assay were used to analyze the expression of Bsep in hilar bile duct tissues of each group. From the second week, the rats in experimental group began to eat less, and their body mass decreased compared with control group and sham operation group. After 6 weeks, we detected hilar cholangiocarcinoma in the hilar bile duct tissues of 18 rats (90%) in the experimental group. In the experimental group with hilar cholangiocarcinoma, we found that the levels of total cholesterol, total bilirubin, and direct bilirubin were higher compared with those in the control group and sham operation group. Simultaneously, muddy stones emerged from the bile ducts of rats in the experimental group. The Bsep/Gapdh mRNA ratio in hilar cholangiocarcinoma, control group and sham operation group differed markedly. Light microscopy revealed a granular pattern of Bsep protein expression which reacted with the anti-Bsep antibody. Each section was randomly divided into six regions, with 80 cells were observed in every region. Sections with > 10% positive cells were designated positive, Sections with < 10% positive cells were designated negative. Each group included 4800 cells. In the experimental group, 1200 cells (25%) were positive, in the control group, 3648 cells (76%) were positive and in the sham operation group 3598 cells (75%) were positive, and this difference was statistically significant. Bsep expression significantly decreased in hilar cholangiocarcinoma of rats than those in control group and sham operation group, suggesting that drugs targeting Bsep are a new strategy for hilar cholangiocarcinoma.


Vascular ◽  
2021 ◽  
pp. 170853812110601
Author(s):  
Cheng-yong Yin ◽  
Jun-jie Fei ◽  
Yu-yin Duan ◽  
Ke Yang ◽  
Xin Li ◽  
...  

Objective This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. Methods The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru – T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. Results After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference ( p < 0.05). Conclusion Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.


1977 ◽  
Author(s):  
H. Heves ◽  
B. Slijepcevic

A disseminated intravascular coagulation (DIC) was induced in rats by infusion of a subthreshold dose of thrombin after producing a hypercoagulable state by i.v, injection of ellagic acid. After pretreatment with a 90 min.-infusion of 50 cas.-u. of plasmin (= plasmin group) or normal saline (= control group) 20 mg AMCHA were applied i.v. for stopping fibrinolysis. Blood parameters of the control group revealed a typical constellation for DIC; additionally, it was observed a highly accellerated 131-I-fibrinogen cata-bolism and an accumulation of 131-I-radioactivity in lungs and kidneys accompanied by haemoglobinaemia and schistocytosis. In spite of the previous defibrination by plasmin, the plasmin group showed partly similar results; the deposition of radioactivity was not so impressive, though plasma haemoglobin levels were neither increased nor schistocytosis observed.Considering the complexity of the presented experimental model, these results show that red cells are not fragmented to schistocytes in absence of fibrinogen because of missing fibrin strands, which probably cause the destruction of red cells in the small blood vessels.


2021 ◽  
Vol 11 (12) ◽  
pp. 2466-2471
Author(s):  
Kang Hu ◽  
Gaojie Qu

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.


2013 ◽  
Vol 716 ◽  
pp. 451-454
Author(s):  
Jing Jing Fang ◽  
An Jun Liu ◽  
Zhen Yuan Zhu ◽  
An Guo Teng ◽  
Guo Qiang Zheng ◽  
...  

The antitumor activity of porcine cartilage polysaccharide was evaluated by vivo animal models. The Ca761 tumor-bearing mice were treated with daily intraperitoneal injections of normal saline (control group) or cartilage polysaccharide (1500, 3000 or 4500mg/kg CPS group) for 14 days. The results demonstrated that CPS could effectively inhibit the tumor growth in Ca761 tumor-bearing mice. The tumor weights of the CPS groups were smaller compared to the control group. While the thymus index, spleen index were higher in the high dose 4500mg/kg CPS group than the control group. These results suggest that CPS might be a strong natural immunomodulator and the antitumor effect of this polysaccharide is associated with its potent immunostimulating effect.


2021 ◽  
Vol 22 (9) ◽  
pp. 4818
Author(s):  
Annica Pröhl ◽  
Milijana Batinic ◽  
Said Alkildani ◽  
Michael Hahn ◽  
Milena Radenkovic ◽  
...  

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.


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