Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici- ty, we observed the effects of ...Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici- ty, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin （a neural precursor cell marker）-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.展开更多
Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or ＂enriched environment＂ as well as pathological conditions such as ischemia, epilepsy or cortical spreading d...Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or ＂enriched environment＂ as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression（CSD） induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation（Sham）, induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs（CSD ＋ 2-VO）. As an additional control, 15 na？ve rats received no intervention except 5-bromo-2′-deoxyuridine（Brd U） treatment for 7 days. Sagittal brain slices（40 μm thick） were co-stained for Brd U and doublecortin（DCX; new immature neuronal cells） on day 9 or Neu N（new mature neuronal cells） on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD ＋ 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in na？ve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD ＋ 2-VO is a direct effect of ischemia, rather than of CSD alone.展开更多
BACKGROUND： Cerebral injury in adult mammals can induce neural precursor cells （NPCs） to proliferate and migrate towards the focal zone, but it is unclear whether endogenous NPCs can migrate towards regions distal ...BACKGROUND： Cerebral injury in adult mammals can induce neural precursor cells （NPCs） to proliferate and migrate towards the focal zone, but it is unclear whether endogenous NPCs can migrate towards regions distal to the hemorrhagic focus or whether NPCs differentiate in the peripheral hemorrhagic region. OBJECTIVE： To investigate the distribution of endogenous NPCs in different brain regions of rats with experimental cerebral hemorrhage, as well as NPC proliferation and differentiation with time. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled animal experiment was performed at the Department of Neurobiology, Luzhou Medical College, between January 2007 and October 2008. MATERIALS： Bromodeoxyuridine （BrdU） was purchased from Roche, Germany. Mouse anti-rat BrdU monoclonal antibody, rabbit anti-nestin polyclonal antibody, rabbit anti-neuron specific enolase （NSE） polyclonal antibody were purchased from Wuhan Boster, China. Rabbit anti-glial fibrillary acidic protein （GFAP） polyclonal antibody was purchased from Sigma, USA. METHODS： Thirty-five adult Sprague Dawley rats were randomly divided into three groups： （1） cerebral hemorrhage group （n = 25）, rats were stereotaxically administered 50 p L autologous arterial blood via the dorsal caudate putamen to induce cerebral hemorrhage; （2） sham-surgery group （n = 5）, rats underwent surgery but did not receive blood injection; （3） blank control group （n = 5）, rats received no surgery and blood administration. At 2 hours after surgery, all rats were intraperitoneally administered BrdU. MAIN OUTCOME MEASURES： Distribution and proliferation of BrdU-positive cells were observed by immunohistochemical staining. BrdU-positive cell differentiation into neurons and glial cells in the peripheral hemorrhagic region was detected by double-label immunofluorescence. RESULTS： Immunohistochemistry results revealed that BrdU-positive cells existed not only in the peripheral hemorrhagic region, such as the subependymal layer展开更多
Malignant glioma remains one of the most intractable of human cancers principally due to the highly infiltrative nature of these neoplasms. The use of neural precursor cells (NPC) has received considerable attention b...Malignant glioma remains one of the most intractable of human cancers principally due to the highly infiltrative nature of these neoplasms. The use of neural precursor cells (NPC) has received considerable attention based on their ability to selectively migrate towards disseminated areas of tumor in vivo and their described ability to deliver tumor-directed therapies specifically to infiltrating tumor cells. Fundamental to optimizing the use of these cells for potential clinical translation is the development of an understanding regarding the biologic cues that govern their ability to migrate towards infiltrative glioma foci. To this end, in this paper we detail that NPC selected for double-expression of the glial-precursor marker A2B5 and the cell-surface chemokine receptor, CXCR4, demonstrate enhanced in vitro gliomadirected tropism. These findings demonstrate the relevance of these markers for the phenotypic segregation of an optimally tumor-tropic NPC sub-population as a means of enhancing NPC-based therapeutic strategies for the treatment of glioma.展开更多
基金the National Natural Science Foundation of China,grants No.30772304,30973166,and 81171863
文摘Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici- ty, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin （a neural precursor cell marker）-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.
基金supported by a grant from Johannes Gutenberg-University
文摘Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or ＂enriched environment＂ as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression（CSD） induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation（Sham）, induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs（CSD ＋ 2-VO）. As an additional control, 15 na？ve rats received no intervention except 5-bromo-2′-deoxyuridine（Brd U） treatment for 7 days. Sagittal brain slices（40 μm thick） were co-stained for Brd U and doublecortin（DCX; new immature neuronal cells） on day 9 or Neu N（new mature neuronal cells） on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD ＋ 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in na？ve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD ＋ 2-VO is a direct effect of ischemia, rather than of CSD alone.
文摘BACKGROUND： Cerebral injury in adult mammals can induce neural precursor cells （NPCs） to proliferate and migrate towards the focal zone, but it is unclear whether endogenous NPCs can migrate towards regions distal to the hemorrhagic focus or whether NPCs differentiate in the peripheral hemorrhagic region. OBJECTIVE： To investigate the distribution of endogenous NPCs in different brain regions of rats with experimental cerebral hemorrhage, as well as NPC proliferation and differentiation with time. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled animal experiment was performed at the Department of Neurobiology, Luzhou Medical College, between January 2007 and October 2008. MATERIALS： Bromodeoxyuridine （BrdU） was purchased from Roche, Germany. Mouse anti-rat BrdU monoclonal antibody, rabbit anti-nestin polyclonal antibody, rabbit anti-neuron specific enolase （NSE） polyclonal antibody were purchased from Wuhan Boster, China. Rabbit anti-glial fibrillary acidic protein （GFAP） polyclonal antibody was purchased from Sigma, USA. METHODS： Thirty-five adult Sprague Dawley rats were randomly divided into three groups： （1） cerebral hemorrhage group （n = 25）, rats were stereotaxically administered 50 p L autologous arterial blood via the dorsal caudate putamen to induce cerebral hemorrhage; （2） sham-surgery group （n = 5）, rats underwent surgery but did not receive blood injection; （3） blank control group （n = 5）, rats received no surgery and blood administration. At 2 hours after surgery, all rats were intraperitoneally administered BrdU. MAIN OUTCOME MEASURES： Distribution and proliferation of BrdU-positive cells were observed by immunohistochemical staining. BrdU-positive cell differentiation into neurons and glial cells in the peripheral hemorrhagic region was detected by double-label immunofluorescence. RESULTS： Immunohistochemistry results revealed that BrdU-positive cells existed not only in the peripheral hemorrhagic region, such as the subependymal layer
文摘Malignant glioma remains one of the most intractable of human cancers principally due to the highly infiltrative nature of these neoplasms. The use of neural precursor cells (NPC) has received considerable attention based on their ability to selectively migrate towards disseminated areas of tumor in vivo and their described ability to deliver tumor-directed therapies specifically to infiltrating tumor cells. Fundamental to optimizing the use of these cells for potential clinical translation is the development of an understanding regarding the biologic cues that govern their ability to migrate towards infiltrative glioma foci. To this end, in this paper we detail that NPC selected for double-expression of the glial-precursor marker A2B5 and the cell-surface chemokine receptor, CXCR4, demonstrate enhanced in vitro gliomadirected tropism. These findings demonstrate the relevance of these markers for the phenotypic segregation of an optimally tumor-tropic NPC sub-population as a means of enhancing NPC-based therapeutic strategies for the treatment of glioma.
