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Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.
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Objective To construct a scientific behavioral research of pasta matrix reaching task (PMRT) and comprehensively evaluate sensory-motor dysfunction caused by brain injury.Methods Twenty-one SD rats were subjected to 14-days pasta matrix grasping training and then were randomly divided into model group (11 rats) and sham group (6 rats).Motor cortex ischemia was induced by injection of endothelin-1 in SD rats.The number of pasta grabed by the injured forelimb and the location in matrix were evaluated daily 7 days after surgery.The infarct volume was measured by Nissl staining at the 7 days,14 days,and 28 days after stroke.Results The number of pasta obtained by rats was reduced from (33.43± 1.02) to (20.57±0.57) at 7 days post stroke in model group,and then increased to (26.85±0.98) at 28 days post stroke,although there was a significant difference between sham group (32.33± 1.45) and ischemic group (t=3.198,P＜0.05).The frequency of retrieval from each slot of the pasta matrix represented that sham group demonstrated a significant gain in performance in the antero quadrant of the matrix compared to ischemic rats by the fourth week after stroke.The stroke volume was decreased from (37.82± 1.17)mm3 at 7 days post-stroke to (24.35±0.38)mm3 at 28 days post-stroke,indicating brain recovery from ischemic injury.Conclusion The pasta matrix reaching task can function as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies and focused rehabilitative training after stroke.
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Objective@#To construct a scientific behavioral research of pasta matrix reaching task (PMRT) and comprehensively evaluate sensory-motor dysfunction caused by brain injury.@*Methods@#Twenty-one SD rats were subjected to 14-days pasta matrix grasping training and then were randomly divided into model group (11 rats) and sham group (6 rats). Motor cortex ischemia was induced by injection of endothelin-1 in SD rats. The number of pasta grabed by the injured forelimb and the location in matrix were evaluated daily 7 days after surgery. The infarct volume was measured by Nissl staining at the 7 days, 14 days, and 28 days after stroke.@*Results@#The number of pasta obtained by rats was reduced from (33.43±1.02) to (20.57±0.57) at 7 days post stroke in model group, and then increased to (26.85±0.98) at 28 days post stroke, although there was a significant difference between sham group(32.33±1.45) and ischemic group (t=3.198, P<0.05). The frequency of retrieval from each slot of the pasta matrix represented that sham group demonstrated a significant gain in performance in the antero quadrant of the matrix compared to ischemic rats by the fourth week after stroke.The stroke volume was decreased from (37.82±1.17)mm3 at 7 days post-stroke to (24.35±0.38)mm3 at 28 days post-stroke, indicating brain recovery from ischemic injury.@*Conclusion@#The pasta matrix reaching task can function as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies and focused rehabilitative training after stroke.
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Angiogenesis is a process that new blood vessels generate on the basis of an original vascular plexus via sprouting or other forms during normal growth and development of an organism or under particular conditions such as wound repairing and ischemic hypoxia. In general, angiogenesis includes five stages: degradation of the vascular basement membrane, endothelial cell proliferation, vascular sprouting, lumen formation and vascular network turning stable and mature. Among ischemic heart diseases, acute myocardial infarction seriously threatens human health, its pathological characteristics include myocardial vascular stenosis and blockage,leading to myocardial infarction. Therefore,the promotion of angiogenesis has become one of the therapies for ischemic heart diseases. A variety of pro-angiogenic cytokines are involved in the process of angiogenesis, such as polypeptide growth factors and lipid mediators. In this paper we review the recent progress in research on the expression of pro-angiogenic factors in myocardium after ischemic myocardial infarction.
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Objective To explore the effects of morroniside on the expression of CD34 in ipsilateral cortex of rats after focal cerebral isch-emia-reperfusion. Methods 45 male Sprague-Dawley rats were divided into sham group (n=9), ischemia group (n=9), and morroniside groups (low, medium and high dosage groups, n=9). The middle cerebral artery were occluded for 30 minutes, and reperfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg, 270 mg/kg after operation. The expression of CD34 in the isch-emic ipsilateral cortex were detected with immunohistochemistry (n=6) and Western blotting (n=3) 7 days after operation. Results The ex-pression of CD34 increased in the ischemia group compared with the sham group, and further increased in the morroniside groups of high dos-age compared with the ischemia group (F>14.865, P<0.001). Conclusion Morroniside could increase the expression of CD34 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, which may promote the angiogenesis and neurogenesis after ischemia.
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@#Objective To investigate the effects of morroniside on the expression of vascular endothelial growth factor (VEGF) and fi-broblast growth factor-2 (FGF-2) in rat cortex after focal cerebral ischemia-reperfusion. Methods 30 male Sprague-Dawley rats were ran-domly divided into sham group, model group, morroniside-low group (30 mg/kg), morroniside-middle group (90 mg/kg) and morroni-side-high group (270 mg/kg). Middle cerebral arteries of rats were occluded for 30 minutes with Longa's method and re-perfused. The ex-pression of VEGF and FGF-2 in the ischemic ipsilateral cortex was detected with Western blotting 7 days after reperfusion. Results The ex-pression of both VEGF and FGF-2 increased in the ischemic ipsilateral cortexin in all the ischemic groups compared with the sham group (P<0.05). The expression of VEGF further increased in a dose-dependent manner in all the morroniside groups compared with that of model group (P<0.05), and the expression of FGF-2 increased in the morroniside-high group (P<0.001). Conclusion Morroniside could increase the expression of VEGF and FGF-2 after ischemia-reperfusion, which might promote angiogenesis.
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Tissues and organs generate angiogenesis under the stimulation of angiogenic factors in physiological or pathological conditions.Multiple signal pathways including VEGF, Notch, Wnt/β-catenin, Ang1(2)/tie2 and PIK-Akt etc.have effects on various stages of angiogenesis.VEGF exerts irreplaceable effects on the whole process of angiogenesis through multiple signal pathways.Over the past few years, new progress has been made in the researches of mechanisms regulating angiogenesis through VEGF-related signal pathways both at home and abroad.These findings provide us new theoretical basis for clarification of the pathogenesis of many diseases and clinical drug development.In this article we will summarize the recent research progress in this field, hoping to provide new possibilities for the treatment of angiogenesis-related diseases.
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@#Objective To explore the effects of morroniside on the expression of Angiopoietin-1 (Ang-1) and Tie-2 in a rat after focal cerebral ischemia-reperfusion. Methods 20 male Sprague-Dawley rats were randomly divided into sham group (n=4), ischemia group (n=4), and morroniside groups (low, medium and high dosage groups, n=4). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ang-1 and Tie-2 increased in the ischemia group compared with the sham group (P<0.01), and both of them further increased in the morroniside groups of high dosage compared with the ischemia group (P<0.01), and the expression of Tie-2 also increased in the morroniside groups of medium dosage (P<0.001). Conclusion Morroniside could increase the expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, suggesting promoting the angiogenesis after ischemia.
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@#Objective To study the effects of morroniside on the expression of matrix metalloproteinase (MMP) -2 and MMP-9 in the peri- infarct cortex 3 days after cerebral ischemia- reperfusion. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of MMP-2 and MMP-9 in peri-infarct cortex were detected with immunohistochemistry staining 3 days after operation. Results The expression of MMP-2 and MMP-9 increased in the ischemia group compared with the sham group (P<0.01), and it decreased in all the morroniside groups compared with the ischemia group (P<0.01). Conclusion Morroniside could decrease the expression of MMP-2 and MMP-9 in the peri-infarct cortex 3 days after ischemia, suggesting protecting the function of blood-brain barrier from ischemia.
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@#Objective To study the effects of morroniside on the expression of Wnt signaling-related transcription factors neurogenin 2 (Ngn2), Pax6 and Tbr2 in the ischemic ipsilateral cortex 7 days after cerebral ischemia-reperfusion in rats. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of Ngn2, Pax6 and Tbr2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ngn2 increased in the ischemia group compared with the sham group (P<0.05), and it further increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference between the ischemia group and sham group in the expression of Pax6, while it increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference among all the groups in the expression of Tbr2. Conclusion Morroniside could increase the expression of Ngn2 and Pax6 in the ischemic ipsilateral cortex 7 days after ischemia-reperfusion in rats, suggesting promoting the neurogenesis after ischemia.
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@#Proliferation and differentiation of neural stem cells is regulated by autologous or external, adjacent or remote cell signaling pathways. This paper reviewed the studies about the Notch, BMP, Wnt, Shh signaling pathways related to brain neurogenesis.
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Proliferation and differentiation of neural stem cells is regulated by autologous or external, adjacent or remote cell signaling pathways. This paper reviewed the studies about the Notch, BMP, Wnt, Shh signaling pathways related to brain neurogenesis.
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Objective To explore the effects of morroniside on the expression of Angiopoietin-1 (Ang-1) and Tie-2 in a rat after focal ce-rebral ischemia-reperfusion. Methods 20 male Sprague-Dawley rats were randomly divided into sham group (n=4), ischemia group (n=4), and morroniside groups (low, medium and high dosage groups, n=4). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expres-sion of Ang-1 and Tie-2 increased in the ischemia group compared with the sham group (P<0.01), and both of them further increased in the morroniside groups of high dosage compared with the ischemia group (P<0.01), and the expression of Tie-2 also increased in the morroni-side groups of medium dosage (P<0.001). Conclusion Morroniside could increase the expression of Ang-1 and Tie-2 in the ischemic ipsilat-eral cortex after ischemia-reperfusion in rats, suggesting promoting the angiogenesis after ischemia.
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Objective To study the effects of morroniside on the expression of Wnt signaling-related transcription factors neurogenin 2 (Ngn2), Pax6 and Tbr2 in the ischemic ipsilateral cortex 7 days after cerebral ischemia-reperfusion in rats. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of Ngn2, Pax6 and Tbr2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ngn2 increased in the ischemia group compared with the sham group (P<0.05), and it further increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference between the ischemia group and sham group in the expression of Pax6, while it increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference among all the groups in the expression of Tbr2. Conclusion Morroniside could increase the expression of Ngn2 and Pax6 in the ischemic ipsilateral cortex 7 days after ischemia-reperfusion in rats, suggesting promoting the neurogenesis after ischemia.
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Objective To study the effects of morroniside on the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the peri-infarct cortex 3 days after cerebral ischemia-reperfusion. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were oc-cluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of MMP-2 and MMP-9 in peri-infarct cortex were detected with immunohistochemistry staining 3 days after operation. Results The expression of MMP-2 and MMP-9 increased in the ischemia group compared with the sham group (P<0.01), and it decreased in all the morroniside groups compared with the ischemia group (P<0.01). Conclusion Morroniside could decrease the expression of MMP-2 and MMP-9 in the peri-infarct cortex 3 days after ischemia, suggesting protecting the function of blood-brain barri-er from ischemia.
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@#Objective To investigate the effect of morroniside on hematocrit percentage in a rat model of focal cerebral ischemia/reperfusion.Methods After the modified model induced with occlusion of middle cerebral artery (MCAO) with suture embolus, morroniside was administered intragastrically at the dose of 30 mg/kg (n=8), 90 mg/kg (n=8), and 270 mg/kg (n=8) once a day for 7 d. Acetyl salicylic acid (ASA) was used as positive drug (n=8). Hematocrit percentage was measured with automatic blood tester. Results Compared with the sham group, hematocrit percentage of the model group significantly increased (P<0.001), but increased less in those treated with morroniside and ASA (P<0.05). Conclusion Morroniside could inhibit the increase of hematocrit percentage in MCAO rats.
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@#Objective To observe the expression of phosphorylated EphrinB2 in brain after focal cerebral ischemia/reperfusion in rats.Methods 24 male Sprague-Dawley rats were randomly divided into sham group (n=12) and model group (n=12). The model group was modeled as middle cerebral artery occlusion and reperfusion with nylon monofilament suture, and then was assessed with Longa's score. The expression of phosphorylated EphrinB2 in cerebral cortex was detected with immunohistochemistry and Western blotting. Results The expression of phosphorylated EphrinB2 and the number of positive cells were significantly higher in the sham group than in the control group (P<0.05). It existed in the vascular endothelium in cerebral cortex. Conclusion EphrinB2 signaling pathway is activated in ischemic stroke.
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@#Parkinson's disease (PD) is one of the most prevalent neurodegenerative movement disorder in human being, characterized by progressive degeneration and lost of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc),causing low level of DA in the nigrostriatal pathway, eventually leading to motor dysfunctions including tremor, rigidity, bradykinesia,and postural instability.The pathology of PD is complex and the etiology remains poorly understood. In recent years,inflammation has been suggested to be involved in the occurrence and development of PD, by activation of microglia and overexpression of the inflammatory factors. And anti-inflammatory drugs has been developed to delay or prevent the progressive course of PD, becoming a new hotspot in treatment of PD. In this review, the latest progresses on the inflammatory mechanisms and anti-inflammatory treatments of PD was introduced.
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@#Atherosclerosis is the common basic pathophysiology progresses of acute cardiovascular and cerebrovascular diseases. Atherosclerotic plaque rupture and consequently thrombosis are the major cause of mobility and mortality in atherosclerosis, and treatment aimed at stabilizing vulnerable plaques is of great clinical importance. However, an ideal drug for stabilizing vulnerable plaques is still lacking. Although Statins are considered as the most potent drugs for stabilizing plaques, their side effects are serious. Traditional Chinese medicine have multi-targets and less side effect, it might be the potential candidate for atherosclerosis treatment. This article reviewed the latest progresses on the stabilizing vulnerable plaques treatments.
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@# Objective To investigate the effects of morroniside on hydrogen peroxide (H2O2)-induced calcium overload and cytotoxicity in SH-SY5Y neuroblastoma cells. Methods SH-SY5Y cells were pre-incubated with morroniside 1, 10, or 100 μmol/L for 24 h prior to exposure to H2O2 300~500 μmol/L for 18 h. The cytosolic free calcium concentration and LDH release were determined. Results The H2O2-induced cytosolic free calcium concentration decreased in the cells pre-incubated with morroniside 10 or 100 μmol/L, while the LDH release level decreased in the cells pre-incubated with morroniside 1, 10 or 100 μmol/L, comparison with the cells exposed H2O2 along. Conclusion Morroniside effects neuroprotection against H2O2-induced calcium overload and cytotoxicity in SH-SY5Y cell.