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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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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 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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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 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 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 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: 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 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 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 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 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 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.
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Objective To investigate the effect of hyperbaric oxygen preconditioning (HOP)on expression of Nogo mRNA,No-go-A and Ng R protein in the cerebral cortex after acute global cerebral ischemia-reperfusion (I/R)in aged rats and to study its mechanism affecting neuroplasticity.Methods Forty-two aged male SD rats were randomly divided into 4 groups:control group (C group,n=6),hyperbaric oxygen group (H group,n=12),cerebral I/R injury group (I/R group,n=12)and HOP group (n=12). The H group and the HOP group were placed in the hyperbaric oxygen cabin for 1 h per day with a oxygen pressure of 0.2 Mpa for successive 5 d,at 24 h after last time of hyperbaric oxygen preconditioning the I/R group and the HOP group adopted the modified Pulsinelli vessel occlusion method for preparing the rat I/R injury model,with global cerebral ischemia for 10 min and reperfusion for 24 h,each 6 rats were randomly taken from the the H group,I/R group and HOP group and their heads were cut off for taking the brain and isolating the cerebral cortex.The real time fluorescence quantification PCR was adopted to detect the expression level of Nogo mRNA and the Nogo-A protein level was detected by Western blot.The rats in various groups were performed the T1 WI and T2WI scanning in the transection position and the coronal positions.Results There were no obvious ischemic brain infarction in the normal control group and the H group,the arc-shaped bilateral cortex ischemic infarct area was clearly seen in the ischemic group,the ischemic infarct area was also seen in the HOP ischemia group,but its area was smaller than which in the ischemic group.Compared with the C group,the expression of Nogo mRNA and the Nogo-A protein in the HOP group was up-regulated(P<0.05);compared with the I/R group,the expression of Nogo mRNA and the Nogo-A protein was down-regulated(P<0.05). Conclusion HOP increases the neuroplasticity and can reduce the cerebral ischemic infarction area in the exceed acute stage of rat acute global cerebral ischemia by inhibiting Nogo mRNA in the cerebral cortex and up-regulating the Nogo-A protein expression.
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Background The retina ischemia reperfusion injury (RIRI) can lead to apoptosis,which is associated with many genes.It is very significant to explore the protection of drugs on RIRI-induced apoptosis.Objective This study was to explore the relationship between the expression of Nogo-A and the cell apoptosis as well as the therapeutic effect of NEP1-40 in RIRI retina.Methods The device of raising intraocular pressure (IOP)was used to elevate the IOP for 60 minutes and then restore the IOP to normal for the establishment of RIRI models.Seventy-eight SD rats were randomized to the normal group,RIRI group and NEP1-40 group.PBS of 5 ml/(kg · d)was injected intraperitoneally in the rats of the RIRI group,and NEP1-40 of 8 mg/(L · kg) was used in the same way in the NEP1-40 group.The rats were sacrificed in overdose anesthesia at 6 hours,12 hours and 1 day,2,3,7 days after RIRI to prepare the retinal specimens.The ultrastructure of rat retinas was examined under the transmission electron microscope.Cell apoptosis was assessed by the TUNEL method,and the apoptotic index (AI) was calculated.The expressions of Nogo-A protein and mRNA in rat retinas were detected by immunohistochemistry and semiquantitative reverse transcription PCR (RT-PCR).Results The ultrastructure of retinal cells were normal in the normal group.Retinal cell organelle dissolution,mitochondria swelling,cavitation,chromatin edge heterochromatin and apoptotic body were seen in the rats of the RIRI group from 12 hours through 7 days after injection.However,only the slight loose of outer membranous disk,inner and outer nuclear layer and retinal ganglion cells,the nucleus gap broadening,shortness of some mitochondrial cristae in the NEP1-40 group.TUNEL-positive cells appeared 6 hours after RIRI and reached peak in 1 day,and gradually declined after that in the RIRI group.A similar pattern was seen in the rats of the NEP1-40 group with a more mild manifestation.Significant differences were seen in the AI values among the different groups at various time points (Fgroup =100.850,P =0.000 ; Ftime =34.309,P =0.000),and the AI values were significantly higher in the RIRI group and NEP1-40 group compared with normal group;while the AI values in the NEP1-40 group was lower than those of the RIRI group (all at P＜0.05).The expressions of Nogo-A protein and mRNA showed a coincident pattern with apoptosis procedure,with a gradually elevated level from 6 hours through 7 days after RIRI and a peak in 2 days,and those in the NEP1-40 group were weaker in comparison with the RIRI group in various time points.Significant differences were detected in the expression of Nogo-A protein and the expression of Nogo-A mRNA among different groups and various time points(protein:Fgroup =164.139,P =0.000;Ftime =21.772,P =0.000.mRNA:Fgroup =93.889,P =0.000 ; Ftime =6.349,P =0.000).Conclusions Nogo-A probably plays an important role in RIRI.NEP1-40 can protect retinal cells from apoptosis following RIRI through down-regulating the expression of Nogo-A.
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OBJECTIVE: To study the effect of Chinese herb Suifukang on the expression of Nogo protein-A in the brain of MCAO rats and explore the action mechanism of its promoting neurogenesis. METHODS: SD rats were selected and randomized into six groups: normal group, control group, treatment group of methylprednisolone, treatment group of Chinese herb Suifukang in large-does, middle-does and small-does. The models of MCAO rats were successfully established by the method of Koizumi. After the surgery, the rats of drug group had been taken orally Suifukang by 10 g · kg-1 crude drug one time daily, and the rest groups had been taken orally equivalence saline once a day. The brain of rats were investigated and the expression of NoGo-A was detected by immunohistology method and RT-PCR method. RESULTS: The expression of NoGo-A in the injured brain was apparently inhibited by Suifukang (P < 0.01). CONCLUSION: Suifukang can inhibit the expression of NoGo-A. So this function may be one of the mechanisms that Suifukang can promote the functional recovery after brain injury. Copyright 2013 by the Chinese Pharmaceutical Association.