AIM To assess the relationship of brain-derived neurotrophic factor(BDNF) with cognitive impairment in patients with type 2 diabetes. METHODS The study included 40 patients with diabetes mellitus type 2(DM2), 37 patie...AIM To assess the relationship of brain-derived neurotrophic factor(BDNF) with cognitive impairment in patients with type 2 diabetes. METHODS The study included 40 patients with diabetes mellitus type 2(DM2), 37 patients with chronic kidney disease in hem dialysis hemodialysis therapy(HD) and 40 healthy subjects. BDNF in serum was quantified by ELISA. The Folstein Mini-Mental State Examination was used to evaluate cognitive impairment.RESULTS The patients with DM2 and the patients in HD were categorized into two groups, with cognitive impairment and without cognitive impairment. The levels of BDNF showed significant differences between patients with DM2(43.78 ± 9.05 vs 31.55 ± 10.24, P = 0.005). There were no differences between patients in HD(11.39 ± 8.87 vs 11.11 ± 10.64 P = 0.77); interestingly, ferritin levels were higher in patients with cognitive impairment(1564 ± 1335 vs 664 ± 484 P = 0.001). The comparison of BDNF values, using a Kruskal Wallis test, between patients with DM2, in HD and healthy controls showed statistical differences(P < 0.001).CONCLUSION Low levels of BDNF are associated with cognitive impairment in patients with DM2. The decrease of BDNF occurs early and progressively in patients in HD.展开更多
Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus ner...Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.展开更多
Objective To observe the changes of the activity of tissue -type plasminogen activa tor(TPA)after asphyxia.Methods As-phyxia was induced in mouse pups by performing a ‘delayed cesarean section’.The experiment was de...Objective To observe the changes of the activity of tissue -type plasminogen activa tor(TPA)after asphyxia.Methods As-phyxia was induced in mouse pups by performing a ‘delayed cesarean section’.The experiment was designed for a co ntrol group and 4asphyctic groups to detect the activity of TPA.Results TPAactivity of brain increased afte r asphyxia(P <0.01).Conclusion TPAincreased after asphyxia might be able to attack the b asement membrane of microvessels,t hen opened the blood -brain barrier a nd induced neuronal damage.展开更多
Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects y-aminobutyric acid type A receptor function i...Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects y-aminobutyric acid type A receptor function in normal neurons. Results from this study demonstrated that y-aminobutyric acid at 100 pmol/L concentration raised the intracellular calcium level in neurons treated with medium from cultured hypoxic astrocytes, and the rise in calcium level could be inhibited by y-aminobutyric acid type A receptor antagonist bicuculline or brain-derived neurotrophic factor receptor antagonist k252a, y-aminobutyric acid type A-gated current induced by 100 IJmol/L y-aminobutyric acid was in an inward direction in physiological conditions, but shifted to the outward direction in neurons when treated with the medium from cultured hypoxic astrocytes, and this effect could be inhibited by k252a. The reverse potential was shifted leftward to -93 mV, which could be inhibited by k252a and Na＋-K＋-CI cotransporter inhibitor bumetanide. Brain-derived neurotrophic factor was released from hypoxic astrocytes at a high level. It shifted the reverse potential of y-aminobutyric acid type A-gated currents leftward in normal neurons by enhancing the function of Na＋-K＋-CI- cotransporter, and caused y-aminobutyric acid to exert an excitatory effect by activating y-aminobutyric acid type A receptor.展开更多
2型糖尿病是一种常见的代谢性疾病,可引起多个器官系统的并发症,包括对大脑结构的影响。随着影像学技术的发展,研究人员能够通过结构磁共振成像(structural magnetic resonance imaging,sMRI)、功能磁共振成像(functional magnetic reso...2型糖尿病是一种常见的代谢性疾病,可引起多个器官系统的并发症,包括对大脑结构的影响。随着影像学技术的发展,研究人员能够通过结构磁共振成像(structural magnetic resonance imaging,sMRI)、功能磁共振成像(functional magnetic resonance imaging,fMRI)和脑电图(electroencephalogram,EEG)等方法直观地评估2型糖尿病患者的脑结构和功能。本文综述了近期基于影像学技术的研究进展,重点探讨了2型糖尿病患者脑结构与糖化血红蛋白之间的关系,并讨论了未来的研究方向。展开更多
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
文摘AIM To assess the relationship of brain-derived neurotrophic factor(BDNF) with cognitive impairment in patients with type 2 diabetes. METHODS The study included 40 patients with diabetes mellitus type 2(DM2), 37 patients with chronic kidney disease in hem dialysis hemodialysis therapy(HD) and 40 healthy subjects. BDNF in serum was quantified by ELISA. The Folstein Mini-Mental State Examination was used to evaluate cognitive impairment.RESULTS The patients with DM2 and the patients in HD were categorized into two groups, with cognitive impairment and without cognitive impairment. The levels of BDNF showed significant differences between patients with DM2(43.78 ± 9.05 vs 31.55 ± 10.24, P = 0.005). There were no differences between patients in HD(11.39 ± 8.87 vs 11.11 ± 10.64 P = 0.77); interestingly, ferritin levels were higher in patients with cognitive impairment(1564 ± 1335 vs 664 ± 484 P = 0.001). The comparison of BDNF values, using a Kruskal Wallis test, between patients with DM2, in HD and healthy controls showed statistical differences(P < 0.001).CONCLUSION Low levels of BDNF are associated with cognitive impairment in patients with DM2. The decrease of BDNF occurs early and progressively in patients in HD.
基金supported by the Natural Science Foundation of China,No.81260295the Graduate Student Innovation Fund of Jiangxi Province of China,No.YC2015-S090
文摘Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.
文摘Objective To observe the changes of the activity of tissue -type plasminogen activa tor(TPA)after asphyxia.Methods As-phyxia was induced in mouse pups by performing a ‘delayed cesarean section’.The experiment was designed for a co ntrol group and 4asphyctic groups to detect the activity of TPA.Results TPAactivity of brain increased afte r asphyxia(P <0.01).Conclusion TPAincreased after asphyxia might be able to attack the b asement membrane of microvessels,t hen opened the blood -brain barrier a nd induced neuronal damage.
基金the National Natural Science Foundation of China, No. 30471657
文摘Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects y-aminobutyric acid type A receptor function in normal neurons. Results from this study demonstrated that y-aminobutyric acid at 100 pmol/L concentration raised the intracellular calcium level in neurons treated with medium from cultured hypoxic astrocytes, and the rise in calcium level could be inhibited by y-aminobutyric acid type A receptor antagonist bicuculline or brain-derived neurotrophic factor receptor antagonist k252a, y-aminobutyric acid type A-gated current induced by 100 IJmol/L y-aminobutyric acid was in an inward direction in physiological conditions, but shifted to the outward direction in neurons when treated with the medium from cultured hypoxic astrocytes, and this effect could be inhibited by k252a. The reverse potential was shifted leftward to -93 mV, which could be inhibited by k252a and Na＋-K＋-CI cotransporter inhibitor bumetanide. Brain-derived neurotrophic factor was released from hypoxic astrocytes at a high level. It shifted the reverse potential of y-aminobutyric acid type A-gated currents leftward in normal neurons by enhancing the function of Na＋-K＋-CI- cotransporter, and caused y-aminobutyric acid to exert an excitatory effect by activating y-aminobutyric acid type A receptor.
文摘2型糖尿病是一种常见的代谢性疾病,可引起多个器官系统的并发症,包括对大脑结构的影响。随着影像学技术的发展,研究人员能够通过结构磁共振成像(structural magnetic resonance imaging,sMRI)、功能磁共振成像(functional magnetic resonance imaging,fMRI)和脑电图(electroencephalogram,EEG)等方法直观地评估2型糖尿病患者的脑结构和功能。本文综述了近期基于影像学技术的研究进展,重点探讨了2型糖尿病患者脑结构与糖化血红蛋白之间的关系,并讨论了未来的研究方向。
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.
