scholarly journals Expression of Slit and Robo During Remodeling of Corticospinal Tract in Cervical Spinal Cord in Middle Cerebral Artery Occlusion Rats

Author(s):  
Zhenhao Ying ◽  
Junxuan Wu ◽  
Wenjun Jiang ◽  
Guoli Zhang ◽  
Weiming Zhu ◽  
...  

Abstract Background: Slits and Robos were associated with the generation of axons of corticospinal tract during the corticospinal tract (CST) remodeling after the cerebral ischemic stroke (CIS). However, little is known about the mechanism of CST remodeling. In this study, we detected the expression of Slits and Robos in middle cerebral artery occlusion (MCAO) rats to investigate the roles of Slits and Robos in the CIS. Methods: MCAO model was established using modified Zea Longa method. Beam walking test (BWT) was conducted to evaluate the motor function. The images of the track of cortical spinal cord beam on day 7, 14 and 21 were observed by anterograde CST tracing. Biopinylated dextan amine (BDA) was used to mark CST anterogradely. Expression of GAP-43 mRNA and GAP-43 protein in cervical spinal cord was detected by Real-Time PCR and Western blot analysis, respectively. The expression of Slit1, Slit2 and Robo1 in cervical spinal cord was detected by immunofluorescence staining.Results: The scores in the model group were significantly reduced compared to sham-operation group on day 7 (P<0.001), 14 (P<0.001) and 21 (P<0.001), respectively. There was no significant difference in the score on day 7, 14 and 21 of the sham-operation groups (P>0.05). In contrast, significant increase was noticed in the scores in model group, presenting a time-dependent manner. More CST staining fibers could be observed at the degenerative side in the model group compared with that of the sham-operation group on day 21. GAP-43 mRNA expression in the model group showed significant increase compared to that of sham-operation group on day 14 (P=0.015) and 21 days (P=0.002). The expression of GAP-43 protein in model group showed significant increase compared to that of sham-operation group on day 14 (P=0.022) and day 21 (P=0.008), respectively. The expression of Slit1 and Slit2 showed increase on day 14 and day 21, while the expression of Robo1 showed significant decrease in MCAO rats.Conclusion: Up-regulation of Slit1 and Slit2 and the downregulation of Robo1 may be related to the axons of CST midline crossing in spinal cord of MCAO rat during the spontaneous recovery of impaired motor function.

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Gang Chen ◽  
Yimin Liang ◽  
Fanghu Chen ◽  
Haifeng Wang ◽  
Guoming Zhu

The objective of this study is to discuss the effect and mechanism of lithium chloride on the rehabilitation of locomotion post spinal cord injury (SCI) by observing the effect of lithium chloride on the expression of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. In total, 36 Sprague-Dawley (SD) rats were randomly divided into the sham operation group (n = 12), model group (n = 12), and lithium chloride group (n = 12). The sham operation group underwent laminectomy, while for the model group and the lithium chloride group with the NYU spinal cord impactor the SCI model was established. Basso, Beattie, and Bresnahan (BBB) score was used to evaluate locomotion after administration for 1, 3, 5, and 7 days, and the tissues were gathered for Nissl staining, transmission electron microscopy, immunofluorescence, and Western blot. With a statistical difference ( P < 0.05) on the 3rd day and significant difference ( P < 0.01) on the 5th day post administration, a higher BBB score was observed in the lithium chloride group indicating that lithium chloride improved the locomotion function after SCI. A better structure and morphology of neuron were observed by Nissl staining in the lithium chloride group. Lithium chloride promoted BDNF secretion from neurons in the spinal cord anterior horn with a significant difference compared to the model group ( P < 0.01). Compared with the model group, lithium chloride significantly promoted the expression of BDNF protein and phosphorylated TrkB protein ( P < 0.05), but no difference in the expression of TrkB was detected. Lithium chloride can alleviate the locomotion function after SCI with a mechanism that it can promote BDNF secretion from neurons in the spinal cord anterior horn and phosphorylation of TrkB to upregulate the BDNF/TrkB pathway supporting survival of neurons and regeneration and remyelination of axons.


2021 ◽  
Vol 11 (10) ◽  
pp. 1932-1939
Author(s):  
Shaofeng Tang ◽  
Nvzhao Yao ◽  
Dahai Qin

Our study assesses the mechanism of Sirt-1 signaling pathway and inflammation changes after spinal cord injury (SCI). SD rats were assigned into Sham group and SCI group. The Sham group only received bites off the corresponding vertebral lamina without the blow operation. The Western Blot method was used to detect Sirt-1 level, ELISA analyzed IL-1β and IL-6 level in the spinal cord tissues along with measuring Sirt-1 and TNF-α level by immunofluorescence staining. Sirt-1 changed with the time after SCI and was significantly higher than sham operation group at 1 day after injury, reaching the highest level at 3 days followed by a decrease. IL-1β and IL-6 after SCI was significantly higher than sham operation group at 1 day after injury. Immunofluorescence double staining showed that Sirt-1 and TNF-α expression in spinal cord tissue after injury were upregulated. The expression of Sirt-1 changed with time after SCI, and was consistent with the trend of changes in inflammatory factors. In conclusion, Sirt-1 is related to the changes of inflammatory factors after SCI, indicating that Sirt-1 may be involved in inflammation after SCI.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Qian Liu ◽  
Hui-Yan Qu ◽  
Hua Zhou ◽  
Jing-Feng Rong ◽  
Tian-Shu Yang ◽  
...  

Background. Luhong formula (LHF)—a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd—is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. Methods. Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-β1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-β1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. Results. LHF significantly lowered the rat’s HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression. Conclusion. LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.


2021 ◽  
Vol 11 (9) ◽  
pp. 1832-1837
Author(s):  
Zhongkui Li ◽  
Wenbo Liu ◽  
Lufang Gao ◽  
Daokang Xiang

MI could affect myocardial function seriously. The action and mechanism of BSMC modified by the transplantation of Toll-like receptor on myocardial function of rats with MI was studied. The sixty SD rats were divided into sham-operation group and model group randomly. The isolated and cultivated BMSC was divided into three groups such as group with added by TLR4 agonist, group with added by TLR-4 antagonist as TAK-242, group with only BMSC. The model of rats with MT was established in model group. BMSC in different group was transplanted into rats respectively. The cardiac function of rats in sham-operation group and model group was observed. The distribution condition of surface molecule in BMSC was detected by FCM. There was expression CD44 (+), CD54 (+), CD90 (+), no expression CD34 (−) from results. It could indicated that BMSCs with high purity was cultivated successfully. The high MT expression was affected by TLR-4 generally which could also illustrate the degree of deformation and necrosis of cardiac muscle cell, could be enhanced in established rat model because of negative regulatory action. The zone of MI in rats could be amplified by TLR-4. The cytobiological function of BMSC could be adjusted by TLR-4 through the transplantation of TLR-4 after there was MI in rats. The cytobiological function of BMSC could be adjusted by TLR-4 through modification of the transplantation of TLT-4 in rats after there was MI in rats. The BMSCs modified by high TLR-4 expression had negative regulatory action on the treatment on MI.


2007 ◽  
Vol 2007 ◽  
pp. 1-11 ◽  
Author(s):  
Zhang Xiping ◽  
Tian Hua ◽  
Chen Hanqing ◽  
Chen Li ◽  
Wang Zhiwei ◽  
...  

Purpose.To observe the protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with severe acute pancreatitis (SAP).Methods.The SAP rat models were randomly divided into the model group, Baicalin-treated group, Octreotide treated group, and sham operation group. The contents of some inflammatory indexes in blood were determined. The rat mortality, pathological changes of heart, the changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels as well as apoptotic index were observed in all groups, respectively, at 3 hours, 6 hours, and 12 hours after operation.Results.The survival rate of model group was less than treated groups at 12 hours, difference was significant. The contents of some inflammatory indexes of the treated groups were lower than those of the model group to various degrees at different time points. The pathological myocardial changes under light microscope were milder in treated groups than in model group. The changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels in all groups were different. There was only a case of myocardial cell apoptosis in an Octreotide-treated group at 6 hours.Conclusion.Baicalin and Octreotide have protecting effects on heart injury of rats with SAP.


2021 ◽  
Author(s):  
Fei Liu ◽  
Liuyang Xie ◽  
Chunhua Liu ◽  
Guilian He ◽  
Chunyun Yuan ◽  
...  

Abstract Background Clinically, Yiqi Dingxuan Yin promotes nerve function recovery and improves nerve function defect symptoms; however, the underlying molecular pathways remain unknown. In this study, we established a rat model of cerebral ischaemia induced by middle cerebral artery occlusion (MCAO). The effects of Yiqi Dingxuan Yin on the neurological function and local neuron morphology were compared with those of butylphthalide, which is used to treat ischemic stroke, and the possible mechanisms of action were explored. Methods Of 97 healthy adult male Sprague‒Dawley rats, 20 were randomly assigned to the sham operation group. The remaining rats underwent MCAO. Model generation was successful in 60 rats, which were randomly divided into a model group, butylphthalide group, and Yiqi Dingxuan Yin group (n = 20/group) administered distilled water, butylphthalide capsule, and Yiqi Dingxuan Yin, respectively. Zea-Longa scores were used to assess the neurological function of the rats at 1, 3, 7, and 14 days. Haematoxylin and eosin staining of brain sections was used to observe morphological changes in the rat hippocampus. Apoptosis of nerve cells was detected using TUNEL staining. The expression levels of erythropoietin/erythropoietin receptor (EPO/EPOR), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF/TrkB) protein in the ischaemic brain tissue were detected using immunohistochemistry. Results The apoptosis rate, and EPO/EPOR, VEGF, and BDNF/TrkB expression levels were higher in the model group than in the sham operation group (P < 0.05). Among MCAO groups, the nerve function deficit score and cell apoptosis rate were lower (P < 0.05), whereas the EPO/EPOR, VEGF, and BDNF/TrkB protein expression levels were higher (P < 0.05) in both the butylphthalide and Yiqi Dingxuan Yin groups than in the model group. Conclusions Yiqi Dingxuan Yin can improve the neural function and morphology of neurons after cerebral ischaemia injury in rats, with a more significant effect at 14 days. This may be related to the upregulation of EPO/EPOR, VEGF, and BDNF/TrkB protein expression, which may promote angiogenesis to improve cerebral blood flow and oxygen supply, thereby protecting the form and function of neurons and promoting the restoration of impaired neural function.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yi Song ◽  
Yi Wang ◽  
Xin Qi ◽  
Xin Kang ◽  
Xiaoguang Lu

Introduction. Severe acute pancreatitis (SAP) is a clinical emergency often accompanied by inflammatory response syndrome (SIRS), which eventually leads to acute lung injury and failure of other organs. The activation of liver Kupffer cells (KCs) plays a major role in the process of SIRS and multiorgan damage caused by SAP. Da-Huang-Fu-Zi-Tang (DHFZT), a traditional Chinese prescription, has been widely used for SAP in the clinic. The present study investigated the activation state of KCs in SAP and the potential mechanism of DHFZT. Methods. A total of 24 Sprague Dawley rats were randomly assigned to four groups: SH (sham operation group + saline enema), SH-DHFZT (sham operation group + DHFZT enema), SAP (model group + saline enema), and SAP-DHFZT (model group + DHFZT enema). Blood samples were drawn from the abdominal aorta for measuring serum endotoxin, amylase, calcium ion, IL-1β, TNF-α, iNOS, and IL-10. Then, the pancreas, lung, liver, and ileum were harvested for histological observation, and the liver was used to detect the level of F4/80, CD86, and CD163 in KCs with immunohistochemistry and western blot. Results. In the SAP group, the CD86+ KCs were significantly increased with a high level of IL-1β, TNF-α, and iNOS, and the organs were impaired. In the SAP-DHFZT group, CD163+ KCs were significantly increased with the high level of IL-10, and the damage to organs was alleviated. Conclusion. These phenomena suggested that the SIRS and multiple organ damage in SAP might be related to the excessive activation of M1 KCs, and DHFZT might alleviate the SIRS by inducing the differentiation of KCs into the M2-type and promote the expression of anti-inflammatory factor IL-10.


2018 ◽  
Vol 17 (5) ◽  
pp. 389-399 ◽  
Author(s):  
Kai Wang ◽  
Weiming Sun ◽  
Linlin Zhang ◽  
Wei Guo ◽  
Jiachun Xu ◽  
...  

Background: Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer’s disease (AD). Objective: To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. Methods: Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Aβ25-35 were built. Morris water maze (MWM) was applied to investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured. Results: The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Aβ25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11±0.42) than that in model group (1.68±0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f- EPSP significantly increased in OA group. Conclusion: The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus.


2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Zhang Xiping ◽  
Chen Li ◽  
Lin Miao ◽  
Tian Hua

Purpose. To study the protecting effects of dexamethasone on thymus of rats with severe acute pancreatitis (SAP).Methods. The SAP rats were randomly assigned to the model group and dexamethasone-treated group, the other normal healthy rats were assigned to the sham operation group. The rat survival, thymus pathological changes, apoptotic index, as well as expression levels of NF-κB, P-selectin, Bax, Bcl-2, and Caspase-3 protein of all groups were observed, respectively, at 3 hours, 6 hours, and 12 hours. The contents of amylase and endotoxin in plasma as well as the contents of TNF-α,PLA2, and NO in serum were determined.Results. There was no marked difference between the model group and treated group in survival. The contents of different indexes in blood of treated group were lower than those of the model group to various degrees at different time points. The thymus pathological score was lower in treated group than in model group at 12 hours.The treated group in Caspase-3 protein expression of thymus significantly exceeded the model group at 12 hours. The apoptotic index was significantly higher in treated group than in model group.Conclusion. Dexamethasone has protecting effects on thymus of SAP rats.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Fan Wang ◽  
Guang-wei Cui ◽  
Le Kuai ◽  
Jian-min Xu ◽  
Ting-ting Zhang ◽  
...  

The role of the acupoint area collagen fibers in the efficacy of acupuncture lifting and thrusting (L&T) manipulation will be explored in this paper. 30 male NZW rabbits were randomly divided into 6 groups: sham operation group (Group N), model group (Group M), acupuncture without manipulation group (Group W), acupuncture L&T manipulation group (Group A), collagenase pretreatment group (Group JM), and collagenase pretreatment + acupuncture L&T manipulation group (Group JA). The bacterial endotoxin was used to generate the rabbit fever models. Acupuncture was applied at IL-11. The levels of IL-1β, TNF-α, and IL-4 and the rectal temperature were measured at 2 h, 4 h, and 6 h after modeling and the collagen fiber morphology at acupoint area was observed after 6 hours.Results.As compared with Group N, the levels of IL-1βand TNF-αin Group M were significantly higher; the level of IL-4 was significantly lower (P<0.05). As compared with Group M, IL-1βand TNF-αin Groups W and A were significantly lower and IL-4 was significantly higher (P<0.05). As compared with Group W, IL-1βand TNF-αin Group A were lower and IL-4 was higher (P<0.05). The collagen fiber in Group A was slightly rough, distorted, and fractured. As shown in studies, the endotoxin-induced inflammatory response can be significantly inhibited by acupuncture whose efficacy can also be significantly improved by the manipulations. Collagenase pretreatment may be the first receptor to the mechanical force of the L&T manipulation.


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