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[Abstract] Objective To elucidate the important role of Nogo-A in climacteric neurodegeneration such as memory impairment by observing memory function and the expression of Nogo-A in hippocampus and striatum of rats under low estrogen condition. Methods Fouthy-five female SD rats were divided into sham operation group, ovariectomized group and ovariectomized estrogen treatment group with 15 rats in each group. Medication was given 2 weeks after ovariectomized. Estrogen treatment group was subcutaneously injected in groin with estrogen [25 μg/ (kg.d)] dissolved in sterile sesame oil. The sham operation group and the ovariectomized group were given the same amount of aseptic sesame oil. Samples were collected after 6 weeks of drug treatment. The difference of memory function of rats in three groups was observed by conditioned fear training experiment, and the expression of Nogo-A in hippocampus and striatum was observed by immunohistochemistry and Western blotting. Results Compared with the sham and estrogen treatment group, memory function in ovariectomized group decreased significantly and the number of Nogo-A positive neurons in hippocampus and striatum of ovariectomized rats was significantly higher than that of sham operation group (P 0. 05). The result of immunoblotting was consistent with the above-mentioned immunohistochemical result. Conclusion The increased expression of Nogo-A in hippocampus and striatum under low estrogen condition may be one of the key reasons for memory impairment in climacteric women.
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Nogo protein is the fourth member of reticulin famity. Nogo mRNA produced by encoding gene transcription, forms three different RNA transcripts due to different promoter and splicing modes, namely Nogo-A, Nogo-B and Nogo-C protein. Nogo protein was first found in the central nervous system, and then proved to be widely expressed in peripheral tissues such as heart, liver and vascular endothelium. Studies have shown that Nogo protein can participate in the regulation of myocardial fibrosis through RhoA/Rho-associated kinase(ROCK) pathway, endoplasmic reticulum stress, Sce61 a and other signaling pathways. In this paper, the relationship between Nogo-A, Nogo-B, Nogo-C and myocardial fibrosis is briefly introduced.
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Objective@#To determine the effect of transplanting bone marrow mononuclear cells (BMMCs) on the expression of glial fibrillary acidic protein (GFAP) and Nogo-A around the ischemic foci after focal cerebral ischemia and reperfusion, and to study any role of BMMCs in nerve function recovery.@*Methods@#BMMCs were isolated from the bone marrow of Sprague-Dawley rats. Cerebral ischemia and reperfusion was performed using a nylon thread to occlude the right middle cerebral artery for 2h followed by 24h of reperfusion. The qualified models were selected according to the Longa scale. The 48 models selected were randomly divided into a model group and an observation group, each of 24. Each group was further divided into 7d, 14d and 21d subgroups. 100μl of BMMCs (5×106 /ml) were slowly injected into the ischemic lateral striata of the observation group. The rats in the model group were similarly injected, but with buffered saline solution. The rats were evaluated using the Longa scale after 7d, 14d and 21d. The rats were then sacrificed and the brain was resected. Immunohistochemical assays quantified the expression of GFAP and Nogo-A around the ischemic foci.@*Results@#Compared with the model group, the rats in the observation group showed less neurological deficit on the 21st day, significantly greater expression of GFAP and significantly less Nogo-A expression on days 14 and 21. Nogo-A expression on the 21st day was also significantly lower than on the 14th day in the observation group.@*Conclusion@#BMMC transplantation can promote recovery from nerve damage after focal cerebral ischemia, which is probably related to enhanced expression of GFAP and restrained expression of Nogo-A in the brain tissues surrounding ischemic lesions.
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The myelin-associated protein Nogo-A was considered to be the axon growth inhibitory factor, which participates in a variety of pathophysiological regulation of nervous system. In recent years, a growing number of studies have shown that Nogo-A protein is closely related to epilepsy by regulating dendritic plasticity, mediating abnormal nerve migration and regulating glial cell activation, etc. This article will review the research progress of Nogo-A in epilepsy in recent years.
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Objective:To explore the neuroprotective effect and mechanism of Buyang Huanwu Tang (BYHWT) on experimental autoimmune encephalomyelitis (EAE) at different stages. Method:The 36 female C57BL/6 mice were immunized subcutaneously with myelin oligodendrocyte glycoprotein peptides (MOG35-55),then randomly divided into 9, 17, 28 d EAE control group. Each BYHWT group was orally given drugs on the 3rd day after immunization (50 g·kg-1·d-1), and EAE control group was given the same volume of normal saline in the same way once a day for 9, 17 and 28 d after immunization. The effect of BYHWT on EAE mice was observed with internationally accepted clinical score. Brain and spinal cord specimens were collected at 9, 17 and 28 d after immunization. The neuroprotective effect of BYHWT was observed by hematoxylin-eosin(HE)staining and solid blue staining (LFB). The expressions of BDNF and GAP-43 in spinal cord and brain were detected by Western blot. Result:After treatment, BYHWT can significantly inhibit myelitis cell infiltration and alleviate myelin loss. Compared with EAE group, the expression of Nogo-A in the spinal cord of each BYHWT group was significantly down-regulated (PPPPConclusion:BYHWT can improve the local nerve growth microenvironment and promote the expression of NTFs, reduce the expressions of neuroinhibitory factors, and play a role in neuroprotection.
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Axonal damage leads to permanent defects in the adult mammals central nervous system. As an important axonal growth inhibitor, Nogo-A and its receptors involve in the regulation of synaptic plasticity in mature neurons of the central nervous system, and play a role in the related neurological diseases, such as spinal cord injury, multiple sclerosis, Alzheimer's disease and posttraumatic stress disorder.
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Objective To investigate the regulation of microtubules by Nogo-A in the dorsal root ganglia during the inflammatory pain. Methods The ipsilateral paw withdrawal latency (PWL) was measured in wild type rats(WT, n = 12) and Nogo-A konck-out (Nogo-A KO) rats (n = 14) after complete Freunds adjuvant (CFA) injection. Western blotting and immunofluorescent staining were used to study the expression of microtubules and phosphorylated collapsin response mediator protein 2(p-CRMP2)in the dorsal root ganglion (DRG) of both groups. Results Knock out of Nogo-A in rats had'attenuated the CFA-induced inflammatory hyperalgesia. The acetylated tubulin was reduced, and the expression of p-CRMP2 was increased in the DRG of the Nogo-A KO rats. Conclusion Nogo-A is involved in the regulation of inflammatory heat hyperalgesia by promoting the microtubule polymerization via CRMP2 pathway.
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@#Objective To investigate the effects of Tuina of Three Handing-Three Points on hindlimb motor function and expression of protein NogoA and its receptor NgR in the spinal cord of rats with sciatic nerve injury. Methods A total of 64 male Sprague-Dawley rats were randomly assigned to normal group (n = 16), sham group (n = 16), model group (n = 16) and Tuina group (n = 16). The model group and Tuina group prepared the sciatic nerve injury model with brace method. Tuina group received Tuina in methods of pressing, strumming and circular rubbing on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) with Tuina manipulation emulator. The rats were assessed with oblique plate test seven days after operation and 20 days after Tuina. Then, the spinal cord tissues were extracted to detect the expression of protein of NogoA and NgR with Western blotting. Results The scores of the oblique plate test decreased in the model group and Tuina group seven days after operation compared with those in the normal group (P < 0.05), while the expression NgR increased (P < 0.05). The scores of the oblique plate test increased in Tuina group compared with those in the model group 20 days after Tuina (P < 0.05), while the expression of NgR decreased (P < 0.05), similar to the normal group (P > 0.05). Conclusion Tuina of Three Handing-Three Points can improve the hindlimb motor function in rats with sciatic nerve injury, which may be related to inhibition of the expression of NgR in the spinal cord after sciatic nerve injury.
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Objective: To investigate effects of Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra on the relative expression of Nogo-A/NgR/RhoA/ ROCK mRNA in acute cerebral infarction rats. Methods: Healthy male SD rats were randomly divided into sham operation group, blank group, low dose, medium dose and high dose Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra group, Ginkgo biloba group, Nimodipine group, and each group was divided into 3 days, 7 days, 14 days three time points. Real-Time quantitative polymerase chain reaction (PCR) was used to detect Nogo-A/NgR/RhoA/ROCK mRNA relative expression changes of acute cerebral infarction rats. Results: Compared with the blank group and the sham operation group, the relative expression level of Nogo-A/NgR/RhoA/ROCK mRNA was increased in the model group both at 3 days, 7 days and 14 days (P ＜ 0.05). After the treatment of Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra, other than there was no significant difference between the low-dose group and the model group except for 7 days, the relative expression level of Nogo-A/NgR/RhoA/ROCK mRNA in Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra groups was lower than that in the model group (P ＜ 0. 05). Conclusion: The relative expression level of Nogo-A/NgR/RhoA/ROCK mRNA in acute cerebral infarction rats can be reduced by Rhizoma Ligustici Chuanxiong and Radix Paeoniae Rubra.
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Objective To investigate the phased expression of gene and protein of NogoA and its receptor (NgR) that affects axon growth of spinal cord injury (SCI), and to explore the time window effect of electroacupuncture on SCI rats. Methods A total of 144 female Sprague-Dawley rats were randomly assigned to sham operation group (group A, n=48) and model group (n=96). In the model group, Allen's method was used to establish SCI rats model, and they were further subdivided into model control group (group B, n=48) and electroacupuncture group (group C, n=48). Group C received electroacupuncture on Dazhui (GV14), Yaoyangguan (GV3), bilateral Ciliao (BL32) and Zu-sanli (ST36) with loose-tight wave, for 20 minutes every day, one day, seven days and 14 days after modeling. The rats at every interventional therapy time were randomly subdivided into two subgroups, which accepted sev-en or 14 days of treatment. Groups A and B were killed and the injured spinal cord tissue was extracted one day, three days, seven days, 14 days and 28 days after modeling, group C at the corresponding time. The hind limb motor function was assessed with BBB score before all of rats were killed. Four samples at every time in each group were randomly selected to detect the expression of mRNA and protein of NogoA and NgR at different stage of SCI using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Results The BBB score began to increase 14 days after modeling, and significantly increased until 28 days after model-ing (P<0.05), compared with one day, three days and seven days after modeling in group B. The BBB score in-creased in group C than in group B at all the time points (P<0.05), except 14 days after electroacupuncture one day after modeling. The BBB score was higher as electroacupuncture intervening seven days and 14 days after modeling than that at one day after modeling in group C, and no significant difference was found between seven days and 14 days of treatment at either electroacupuncture time point (P>0.05). The expression of gene and pro-tein of NogoA and NgR in group B was in the increasing tendency after SCI, and was at the peak until 21 days af-ter modeling, and was higher in group B than in group A at each time point (P<0.01). The expression of gene and protein of NogoA decreased at all the time points in group C than in group B (P<0.05), except seven days of elec-troacupuncture intervening one day after modeling in the expression of NogoA mRNA (P>0.05). The expression of gene and protein of NogoA and NgR was lower as electroacupuncture intervening 14 days after modeling than one day after modeling in group C (P<0.05). There was no significant difference in the expression of gene and protein of NogoA and NgR between electroacupuncture intervening 14 days and seven days after modeling, and seven days and one day after modeling (P>0.05); as well as between seven days and 14 days of treatment at each time point (P>0.05). Conclusion Elerctroacupuncture could improve the hind limb motor function, which may associate with the inhibition of the expression of gene and protein of NogoA and NgR in injured spinal cord of rats after SCI. Elerctroacu-puncture is effective in the treatment of SCI at the early time, however, it is much better in the recovery stage.
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OBJECTIVE: α-synuclein, Nogo-A and Ubiquitin C-terminal hydrolase L1 (UCH-L1) have neuromodulatory roles for human brain. Therefore, abnormalities of these molecules are associated with neuropsychiatric disorders. Although some serum studies in the other disorders have been made, serum study of α-synuclein, Nogo-A and UCH-L1 is not present in patients with schizophrenia and healthy controls. Therefore, our aim was to compare serum levels of α-synuclein, Nogo-A and UCH-L1 of the patients with schizophrenia and healthy controls. METHODS: Forty-four patients with schizophrenia who is followed by psychotic disorders unit, and 40 healthy control were included in this study. Socio-demographic form and Positive and Negative Syndrome Scale (PANSS) was applied to patients, and sociodemographic form was applied to control group. Fasting bloods were collected and the serum levels of α-synuclein, Nogo-A and UCH-L1 were measured by ELISA method. RESULTS: Serum α-synuclein [patient: 12.73 (5.18–31.84) ng/mL; control: 41.77 (15.12–66.98) ng/mL], Nogo-A [patient: 33.58 (3.09–77.26) ng/mL; control: 286.05 (136.56–346.82) ng/mL] and UCH-L1 [patient: 5.26 (1.64–10.87) ng/mL; control: 20.48 (11.01–20.81) ng/mL] levels of the patients with schizophrenia were significianly lower than healthy controls (p<0.001). CONCLUSION: Our study results added new evidence for explaining the etiopathogenesis of schizophrenia on the basis of neurochemical markers.
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Humans , Biomarkers , Brain , Enzyme-Linked Immunosorbent Assay , Fasting , Methods , Psychotic Disorders , Schizophrenia , Ubiquitin ThiolesteraseABSTRACT
Objective To observe the effect of edaravone (ED) on cognition function and expression of Nogo-A in prefrontal cortex neuron of rats with serious intermittent hypoxia.Methods Ninety-six adult male Wistar rats were randomly divided into normal control group, chronic intermittent hypoxia (CIH) model group and ED group, 32 rats in each group. The rat model of CIH was reproduced in a low oxygen box at 08:00-15:00 every day: alternatively, different flow rates of nitrogen and compressed air were given, 120 seconds being one cycle, maintaining the oxygen concentration at 5%-21% in the low oxygen chamber; the normalcontrol group was continuously under the circumstance fulfilled with compressed air. The rat in ED group was given intravenous injection of 3 mg/kg ED in a tail vein at 07:00 daily. After modeling for 7, 14, 21, 28 days, the learning and memory functions of rats were assessed with the Morris water maze test, and the reactive oxygen species (ROS) content in the rat prefrontal lobe tissue was detected; the level of Nogo-A protein expression in the rat prefrontal cortex was examined by immunohistochemical method .Results ① Rat learning results: in CIH model group, with the time prolongation escaping latency period was gradually longer, since 14 days after the modeling, the difference was statistically significant compared with that in normal control group, while the learning time in ED group was obviously shorter than that in the CIH model group (seconds: 14 days was 26.97±3.35 vs. 34.95±3.36, 21 days was 32.78±4.59 vs. 46.72±4.11, 28 days was 41.39±3.84 vs. 57.35±3.72, allP < 0.05). ② Rat memory results: the rats in CIH model group, with the time prolongation crossing the target quadrant time was gradually shorter, since 14 days after the modeling, the difference was statistically significant compared with that of the normal control group, while the memory time in the ED group was obviously longer than that of the model group (seconds: 14 days was 42.72±3.35 vs. 39.88±3.56, 21 days was 40.48±4.62 vs. 28.72±3.93, 28 days was 31.13±3.46 vs. 22.79±3.24, allP < 0.05). ③ ROS content: with the time prolongation, ROS content was gradually increased in CIH model group, but the ROS content in ED group was significantly lower than that in CIH model group at various time points (MU/L: 7 days was 13.27±0.23 vs. 17.68±0.51, 14 days was 15.51±0.28 vs. 20.41±0.65, 21 days was 20.29±0.44 vs. 23.86±0.35, 28 days was 24.46±0.53 vs. 30.43±0.85, allP < 0.05). ④ Protein expression of Nogo-A: with the time prolongation, the protein expression of Nogo-A was gradually increased in CIH model group, they reached the peak on the 14th day, the expression of Nogo-A [absorbance (A) value] in ED group were significantly lower than that in CIH model group at each time point (×103: 7 days was 4.80±0.70 vs. 5.99±0.62, 14 days was 5.89±0.90 vs. 7.42±0.66, 21 days was 4.92±0.64 vs. 5.90±0.37, 28 days was 3.59±0.59 vs. 4.27±0.40, allP < 0.05).Conclusions The mechanism of ED has a valid therapeutic effect on the cognitive dysfunction induced by serious intermittent hypoxia in rats, ED can remove oxygen free radicals and inhibit the protein expression of Nogo-A in the prefrontal cortex, so ED can alleviate the damage of cognitive function in rats with CIH.
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Objective To observe the changes of hippocampal NogoA-NgR1 signaling on postoperative cognitive function (POCD) in aged mice, and explore the potential underling mechanism.Methods Isoflurane anesthesia and laparotomy were applied to establish the POCD model.Forty aged male C57BL/6 mice were randomly divided into the following four groups (n=10): group O2+saline (group OS), group O2+NEP1-40 (group ON), group isoflurane anesthesia+laparotomy surgery+saline (group SS), and group isoflurane anesthesia+laparotomy surgery+NEP1-40 (group SN).Cannula placement was performed into lateral ventricle 7 days before the surgery.Animals were subjected to an administration of NEP1-40 (20 μg/2 μl) or isochoric saline via intracerebroventricular injection once daily for 8 consecutive days, injection was given from 2 h before isoflurane anesthesia to the last behavioral test.Open field test was performed at 5th d after operation.Contextual and cued fear conditioning training and testing were exhibited at 6th and 7th d after operation, respectively.The hippocampus was harvested 2 h after the behavioral test.Western blot was used to detect the expressions of NogoA, NgR1, RhoA, ROCK2 and GAP43.Golgi staining was applied to measure the changes of dendritic spines in hippocampal CA1 area.Results Compared with the groups OS and ON, the freezing time in the contextual fear conditioning test was significantly decreased, the contents of NogoA, NgR1, RhoA and ROCK2 were significantly increased, the content of GAP43 and the number of dendritic spine were significantly decreased in group SS (P<0.05).Compared with the group SS, the freezing time in the contextual fear conditioning test was significantly increased, the contents of RhoA and ROCK2 were significantly decreased, the content of GAP43 and the number of dendritic spine were significantly increased in group SN (P<0.05).Conclusion Over-activated of hippocampal NogoA-NgR1 signaling participated in the pathogenesis of POCD in aged mice.
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Objective:To study the dynamic expression of Nogo-A in hippocampus of rats after carbon monoxide poisoning,and to explore the effect and influence of Nogo-A in the damage to nervous system after carbon monoxide poisoning.Methods:Thirty male SD rats were randomly divided into NC group(n=6),CO group(n=6),CO-24 h group(n=6),CO-48 h group(n=6),CO-7d group(n=6).The method of injection CO gas was used to establish the carbon monoxide poisoning model.Then immunohistochemical (IHC) and Western blot (WB) techniques were used to observe dynamic expression of Nogo-A in hippocampus of rats at several time intervals after carbon monoxide poisoning and to analyze its change law.Results:IHC results showed that the average optical density value of expression of Nogo-A in NC group,CO group,CO-24 h group,CO-48h group and CO-7d group were 0.0928± 0.0038,0.01172± 0.0042,0.1452± 0.0056,0.1271 ± 0.0057,0.1088± 0.0055.WB results showed that the expression of Nogo-A in hippocampus after carbon monoxide poisoning was significantly higher than that in NC group(P＜0.05),and reached the highest level at 24 h,then had a gradual recovery after 24h.The expression of Nogo-A decreased obviously,but still higher than that of NC group by day 7 (P＜0.05).Conclusions:In this study,the increase of expression of Nogo-A was associated with carbon monoxide poisoning.The expression of Nogo-A reached the highest level at 24h,then had a gradual recovery after 24 h.
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Objective To observe the effect of aerobic exercise preconditioning on growth-associated protein-43 (GAP-43) and Nogo-A in rats after cerebral ischemia/reperfusion. Methods Sprague-Dawley rats were equally divided into sham group (n=40), cerebral ischemia/reperfusion group (n=40) and aerobic exercise preconditioning group (n=40), and global cerebral ischemia model was formed with modified four-vessel occlusion. The rats was sacrificed six hours, one day, three days and seven days after ischemia, respectively. The hippocampus neural cells were observed in five rats with HE staining and immunohistochemistry of GAP-43 and Nogo-A, and the other five rats were test-ed with RT-PCR of GAP-43 and Nogo-A. Results Compared with those in the cerebral ischemia/reperfusion group, the apoptotic neurons and expression of GAP-43 significantly increased all the time points in the aerobic exercise preconditioning group (P<0.01), while the ex-pression of Nogo-A decreased (P<0.01). Conclusion Aerobic exercise preconditioning can promote the regeneration of neuronal cells and axon after cerebral ischemia/reperfusion injury, which is related to the regulation of GAP-43 and Nogo-A.
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Objective To observe the effect of exhaustive exercise preconditioning on GAP?43 and Nogo?A in rats with cerebral ischemia reperfusion. Methods 90 rats were randomly divided into sham oper?ation group,group of cerebral ischemia reperfusion(I/R) and exhaustive exercise preconditioning group.Rats were sacrificed at 6 h,1 d,3 d and 7 d respectively after injury. Neural functions were detected by shuttle box. Morphological changes of hippocampal neural cells were observed by HE staining. Expressions of GAP?43 and Nogo?A were detected respectively by immunohistochemistry and RT?PCR technology. Re?sults Compared with the sham group,the death rate of apoptotic neurons in I/R group was decreased( 6 h:(30.97±2.09)%,1 d:(38.41±1.10)%,3 d:(46.81±2.04)%,1 d:(43.46±1.57)%),the index of learning and memory ability(AARR?7 d:(38.00±12.60)%,PAL?7 d:(27.90±1.79)s) and expression of GAP?43 were decreased(6 h:(2.89±0.85),1 d:(4.06±0.25),3 d:(4.78±0.98),7 d:(7.02±0.21)),the expression of Nogo?A was increased(6 h:(2.93±0.19),1 d:(5.47±0.32),3 d:(4.62±0.26),7 d:(4.12±1.11))(P<0.05).Compared with I/R group,the death rate of apoptotic neurons in exhaustive exercise preconditioning group were decreased,the index of learning and memory ability(AARR?7 d:(20.66±7.60)%,PAL?7 d:(35.53±2.41)s) and expression of GAP?43 were decreased(6 h:(2.03±0.14),1 d:(2.92±0.27),3 d:(3.35±0.34),7 d:(5.24±0.52)),the expression of Nogo?A were increased(6 h:(3.92±0.51),1 d:(6.90± 0.79),3 d:(5.87±0.48),7 d:(5.37±0.50))(P<0.05). Conclusion Exhaustive exercise preconditioning ag? gravates the injury of neurons and neural function,which is related to the regulation of GAP?43 and Nogo?A in the hippocampus of rats.
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Objective To determine the effect of willed movement on the expression of Nogo-A and Rho-associated kinase (ROCK) in adult rats with cerebral ischemia.Methods Cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion (MCAO) for 2 h,followed by a 24 h reperfusion in 54 adult rats and the degree of their neurological deficit was evaluated using Longa scale.They were then divided randomly into 3 groups,namely the MCAO group,the environmental modification (EM) group,and the willed movement (WM) group.The rats of MCAO group were raised in a regular breeding box,where they could get food and water freely.Meanwhile,those of the other two groups were raised in a homemade box.For the WM group,the water bottle and food were located on the roof of the homemade box.In each group,six rats were killed on day 3,7 and 15 after reperfusion and their neurological deficits were evaluated respectively.Immunohistochemistry assay was employed to examine the expression of Nogo-A and ROCK in the brain tissue around the ischemic foci.Results The rats of the WM group showed lessened neurological deficits on day 15 compared with the model and EM group.Their expression of Nogo-A decreases from(28.92 ± 2.17)/hpf on day 7 to (24.38 ± 2.29)/hpf on day 15 and that of ROCK did from (40.03 ± 2.14)/hpf to (38.08 ± 2.07) / hpf,lower than those of the model and EM group.However,no significant differences were found in the expression of Nogo-A and ROCK between the model group and EM group at any time points.Conclusion Willed movement could promote the functional recovery of neurological deficits in rats with ischemia after reperfusion,which is probably in relation to restrained expression of Nogo-A and Rho-associated in the tissue around the brain ischemic foci.
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Objective To investigate regeneration and repair effect after ChABC,GDNF and Nogo-A Ab combination treatment for experimental spinal cord injury model.Methods Rat (T7-8 )complete spinal cord injury crosscutting animal model was established.The SD rats were randomly divided into 6 groups:normal group, sham operation group,simple transection group,A (ChABC)group,G (GDNF)group,N (Nogo-A antibody) group,and AGN (ChABC+GDNF+Nogo-A antibody)group.At 24 w after spinal cord injury,BDA tracer,NF-200,GAP-43,and GFAP immunohistochemistry were evaluated.Results BDA tracer of A group,G group and N group showed dye light,the proximal end of damaged zone showed the blue tracer particles,while damaged zone showed few blue regenerated nerve fibers.AGN group showed visible blue nerve fibers through the damaged zone and the distal segment in the damaged zone;the central zone of injury vacuolar degeneration showed the blue dyed fibers.NF-200 immunohistochemical staining showed NF-positive staining in A group,AGN was stronger than that in control group and simple transection group (P 0.05 ).SEP wave was detected in control group and AGN group,while the latency time was longer in AGN group than in control group.Conclusion ChABC,GDNF,and anti-Nogo-A antibody used alone or in combination can improve spinal cord injury and nerve cell function,and the joint application could improve regeneration after spinal cord injury than any monotherapy.
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Objective To investigate the effect of transplantation with the three-dimensional spheroid-cultured mesenchymal stem cells (MSCs) on the expression of Nogo-A and NgR in rats with cerebral ischemia-reperfusion injury. Methods The experimental animals were randomly divided into Sham group, Vehicle group and MSCs treated group. The model of focal ischemia-reperfusion in rats was induced by intraluminal middle cerebral artery (MCA) occlusion with a nylon monofilament suture in Vehicle group and MSCs treated group. The fishing line was unpluged for reperfusion 2 h after ischemia and MSCs were transplanted in MSCs treated group one day later. Equivalent medium solution was given to the Vehicle group 1 d later. On the 1st day, 3rd day, and 7th day after transplantation, the neuromotor function of the animals was detected. The brain tissue of rats was harvested for RT-PCR detection of Nogo-A and NgR mRNA expression in the brain tissue of rats, and Western blotting analysis was used to detect the expression of Nogo-A and NgR protein. Results Compared with the Vehicle group, the neuromotor function was significantly improved in MSCs treated group on the 7th day; and the expressions of Nogo-A and NgR mRNA and protein were significantly down-regulated in MSCs treated group on the 1st day, 3rd day, and 7th day after transplantation (P<0.05). Conclusion Transplantation of the three-dimensional spheroid-cultured MSCs can improve the neuromotor function following cerebral ischemia/reperfusion injury, and its mechanism may be associated with down-regulation of Nogo-A and NgR in the brain tissue.
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Objective To study the effects of Fasudil on expression of Nogo-A and NF200 in neonatal hypoxic-ischemic brain damage(HIBD) rats.Methods One hundred and twenty 7-day-old Wistar rats were divided into 3 groups with random number table:Sham operation group (n =40),HIBD group (n =40) and Fasudil group (n =40).Sham group only separated from the common carotid artery,without ligation,direct suture the incision does not do hypoxia; HIBD group were injected with saline; Fasudil group was injected with fasudil(10 mg/kg).The rats were killed at 6 h,12 h,24 h,72 h,7 d,after administration.The pathological changes were observed by means of HE.The expression of Nogo-A and NF200 was studied with immunohistochemical staining.Results 1.Naked eye observation:Sham group bilateral symmetrical cerebral hemispheres; HIBD group of brain edema aggravated,the visible hemisphere focal necrosis; fasudil treatment group of edema than HIBD group ease.2.HE stain:the structure and shape of brain in Sham operation group were normal.In HIBD group,the cells became edema,karyopyknosis,lyse,and the inflammatory cells became more.The number of edema cells and karyopyknosis decreased in Fasudil group.3.Immunohistochemical stain:there were less expressions of Nogo-A in Sham operation group.It increased slightly after 12 h in HIBD group but decreased later.The expression of Nogo-A in Fasudil group was less than the other two groups at any time except 6 h (P ＜0.01).There was more expression in HIBD and Fasudil group compared with Sham operation group(P ＜0.01).NF200 was less expression in Sham operation group.NF200 appeared after 6 h and became less after 12 h.The expression of NF200 was at 24 h and later became more.The expression of NF200 in Fasudil group was more with HIBD group at each different time (P ＜ 0.01).The expressions of NF200 in Fasudil and HIBD group were more compared with Sham operation group.Conclusions Fasudil can rehabilitate the damaged axon and promote nerve regeneration through controlling the Rho/Rock and make the expression of NF200 increase.