Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an ...Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.展开更多
目的探讨培元通脑胶囊对脑缺血大鼠前额叶葡萄糖代谢及行为学变化的影响。方法 60只大鼠随机分为假手术组、模型组、尼莫地平组和培元通脑组,每组15只。除假手术组外其余各组大鼠应用双侧颈总动脉永久性结扎剪断血管的方法制备脑缺血低...目的探讨培元通脑胶囊对脑缺血大鼠前额叶葡萄糖代谢及行为学变化的影响。方法 60只大鼠随机分为假手术组、模型组、尼莫地平组和培元通脑组,每组15只。除假手术组外其余各组大鼠应用双侧颈总动脉永久性结扎剪断血管的方法制备脑缺血低灌注大鼠模型,在术前及术后即刻观察脑血流灌注量变化情况。应用Morris水迷宫(Morris water maze,MUM)观察脑缺血大鼠在空间探索试验中第一象限路程与总路程比值和游泳速度变化、穿越平台次数比较,反向平台延时任务完成情况比较,应用micro-PET观察大鼠前额叶神经细胞18F-FDG摄取变化情况。结果大鼠双侧颈总动脉结扎术前及术后模型组、尼莫地平组、培元通脑组即刻脑血流灌注量明显下降,与术前比较有统计学差异(P<0.01);模型组脑缺血大鼠游泳速度低于培元通脑组(P<0.05),在NE象限游泳路程与总路程比值低于培元通脑组(P<0.05),撤出水下平台后穿越目标区域的次数明显少于培元通脑组(P<0.05),模型组脑缺血大鼠在反向平台模型组与假手术组比较,逃避潜伏期延长,差异具有统计学意义(P<0.01),而反向平台延时任务中模型组与培元通脑组比较逃避潜伏期延长(P<0.05),前额叶神经细胞18F-FDG标准摄取值培元通脑组大鼠的标准摄取值高于模型组大鼠(P<0.05)。结论培元通脑胶囊通过益肾填精,熄风通络能够填精补髓益脑,改善前额叶神经细胞葡萄糖代谢,改善脑缺血大鼠在水迷宫中的空间参考记忆。展开更多
One group of six male control rats [12 months old] and one group of six male rats of the same age, singularly maintained in a cage, and treated with acetyl-L-carnitine-HCl [(gamma-trimethyl-beta-acetyl-butyrobetaine-H...One group of six male control rats [12 months old] and one group of six male rats of the same age, singularly maintained in a cage, and treated with acetyl-L-carnitine-HCl [(gamma-trimethyl-beta-acetyl-butyrobetaine-HCl: Sigma-Tau code ST200 or ALCAR: 60 mg/kg/day[7]/po)] for six months were tested in the spatial learning/memory Morris mazewater task and for atrophy and cell loss in seven myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions [Freddi et al., 2009]. Coronal sections 25 ?m thick were cut through the BF regions and processed every 200 ?m for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (average ± SD 28.3 ± 12.4 s vs. 61.16 ± 4.67 s;t = 6.07, DOF = 10, P = 0.0001). Degenerative morphological changes in the BF ChAT-positive cells were observed in the substantia innominata pars anterior of the control rats but not in the treated animals (P < 0.05). In the BF, the counted and estimated average number of ChAT + cells in the 12-month-old ALCAR-treated rats (ChAT-ALCAR-12+ [Nos. 2,3,4]) was higher but not significantly (15.288 ± 3281) than that counted and estimated in the 12-month-old control rats [(ChAT-CT-12 [Nos. 1,2,3]) (11.508 ± 3868), t = 1.82, DOF = 10, P = 0.319]. In the substantia innominata pars posterior, the ChAT+ cells were significantly more numerous (P < 0.05) in the 12-month-old ALCAR-treated rats (ChAT-ALCAR-12 + [Nos. 2,3,4]) than in the control rats (ChAT-CT-12 [Nos. 1,2,3]). Above all, these results dem-onstrate that treatment with ALCAR from the age of 6 up to 12 months significantly attenuated spatial learning/memory impairment on the Morris maze-water behavioral task (P < 0.001) and also importantly reduced degeneration in size and number of cholinergic cells in the nucleus basalis magnocellularis of the BF. Accordingly, the surviving cholinergic neurons found in the BF of the ALCAR-treated rats might play an important role in modulating cortical activity and facilitating processes of attention, learning and memory.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81601961(to KWY),81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.
文摘目的探讨培元通脑胶囊对脑缺血大鼠前额叶葡萄糖代谢及行为学变化的影响。方法 60只大鼠随机分为假手术组、模型组、尼莫地平组和培元通脑组,每组15只。除假手术组外其余各组大鼠应用双侧颈总动脉永久性结扎剪断血管的方法制备脑缺血低灌注大鼠模型,在术前及术后即刻观察脑血流灌注量变化情况。应用Morris水迷宫(Morris water maze,MUM)观察脑缺血大鼠在空间探索试验中第一象限路程与总路程比值和游泳速度变化、穿越平台次数比较,反向平台延时任务完成情况比较,应用micro-PET观察大鼠前额叶神经细胞18F-FDG摄取变化情况。结果大鼠双侧颈总动脉结扎术前及术后模型组、尼莫地平组、培元通脑组即刻脑血流灌注量明显下降,与术前比较有统计学差异(P<0.01);模型组脑缺血大鼠游泳速度低于培元通脑组(P<0.05),在NE象限游泳路程与总路程比值低于培元通脑组(P<0.05),撤出水下平台后穿越目标区域的次数明显少于培元通脑组(P<0.05),模型组脑缺血大鼠在反向平台模型组与假手术组比较,逃避潜伏期延长,差异具有统计学意义(P<0.01),而反向平台延时任务中模型组与培元通脑组比较逃避潜伏期延长(P<0.05),前额叶神经细胞18F-FDG标准摄取值培元通脑组大鼠的标准摄取值高于模型组大鼠(P<0.05)。结论培元通脑胶囊通过益肾填精,熄风通络能够填精补髓益脑,改善前额叶神经细胞葡萄糖代谢,改善脑缺血大鼠在水迷宫中的空间参考记忆。
文摘One group of six male control rats [12 months old] and one group of six male rats of the same age, singularly maintained in a cage, and treated with acetyl-L-carnitine-HCl [(gamma-trimethyl-beta-acetyl-butyrobetaine-HCl: Sigma-Tau code ST200 or ALCAR: 60 mg/kg/day[7]/po)] for six months were tested in the spatial learning/memory Morris mazewater task and for atrophy and cell loss in seven myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions [Freddi et al., 2009]. Coronal sections 25 ?m thick were cut through the BF regions and processed every 200 ?m for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (average ± SD 28.3 ± 12.4 s vs. 61.16 ± 4.67 s;t = 6.07, DOF = 10, P = 0.0001). Degenerative morphological changes in the BF ChAT-positive cells were observed in the substantia innominata pars anterior of the control rats but not in the treated animals (P < 0.05). In the BF, the counted and estimated average number of ChAT + cells in the 12-month-old ALCAR-treated rats (ChAT-ALCAR-12+ [Nos. 2,3,4]) was higher but not significantly (15.288 ± 3281) than that counted and estimated in the 12-month-old control rats [(ChAT-CT-12 [Nos. 1,2,3]) (11.508 ± 3868), t = 1.82, DOF = 10, P = 0.319]. In the substantia innominata pars posterior, the ChAT+ cells were significantly more numerous (P < 0.05) in the 12-month-old ALCAR-treated rats (ChAT-ALCAR-12 + [Nos. 2,3,4]) than in the control rats (ChAT-CT-12 [Nos. 1,2,3]). Above all, these results dem-onstrate that treatment with ALCAR from the age of 6 up to 12 months significantly attenuated spatial learning/memory impairment on the Morris maze-water behavioral task (P < 0.001) and also importantly reduced degeneration in size and number of cholinergic cells in the nucleus basalis magnocellularis of the BF. Accordingly, the surviving cholinergic neurons found in the BF of the ALCAR-treated rats might play an important role in modulating cortical activity and facilitating processes of attention, learning and memory.
