State Key Laboratory of Medical Neurobiology

Shanghai, China

State Key Laboratory of Medical Neurobiology

Shanghai, China
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Su J.,Shanghai JiaoTong University | Zhou H.,Fudan University | Tao Y.,Ouyang Hospital | Guo J.,State Key Laboratory of Medical Neurobiology | And 7 more authors.
PLoS ONE | Year: 2015

Granulocyte-colony stimulating factor (G-CSF) has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of GCSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA) and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM) revealed that GCSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/ 2 (ERK1/2) and Akt, and deactivation of c-Jun N terminal kinase (JNK) and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogenactivated protein kinases (MAPK) and Akt signaling cascades. G-CSF may represent a promising therapeutic agent for diabetic stroke. Copyright: © 2015 Su et al.


Jiang S.,Fudan University | Li Z.-Y.,Shanghai JiaoTong University | Hua X.-Y.,Fudan University | Xu W.-D.,Fudan University | And 3 more authors.
Microsurgery | Year: 2010

The purpose of our study was to establish the profile of cortical reorganization in whole BPAI on rats and evaluate changes of cortical reorganization after repair of the median nerve with the contralateral C7 root transfer. Forty adult SD rats underwent whole roots avulsion of left brachial plexus, among them 20 received contralateral C7 root transfer to the injured median nerve. Intracortical microstimulation was performed in primary motor cortex (M1) at intervals of 3, 5, 7, and 10 months, postoperatively. The maps of motor cortical responses were constructed. Five normal rats were used as the control. Results showed that stimulating right M1 elicited motion of left vibrissae, submaxilla, neck, back, and left hindlimb after left BPAI, among them neck representation area replaced the forelimb area throughout the reorganization process. The left forelimb representation area was found in the left motor cortex 5 months after the contralateral C7 root transfer and existed in both motor cortexes at 7th postoperative month. The left forelimb representation area was detected only in rightmotor cortex at 10thmonth, postoperatively. In conclusions, after the contralateral C7 root transfer for repair of the median nerve in BPAI, the cortical reorganization occurred in a time-dependent reorganization. The findings from this study demonstrate that brain involves in the functional recovery after BPAI and repair with nerve transfer and suggest that efforts to improve the results fromnerve repair should address the peripheral nerve as well as the brain. © 2010 Wiley-Liss, Inc.


Han P.,State Key Laboratory of Medical Neurobiology | Han P.,Shanghai JiaoTong University | Liu S.,State Key Laboratory of Medical Neurobiology | Zhang M.,State Key Laboratory of Medical Neurobiology | And 4 more authors.
PLoS ONE | Year: 2015

Although acupuncture is widely used to manage pain, it remains highly controversial, largely due to the lack of a clear mechanism for its benefits. Here, we investigated the role of IL-33, a novel interleukin (IL)-1 family member, and its receptor ST2 in the analgesic effects of electroacupuncture (EA) on formalin-induced inflammatory pain. The results showed that 1) EA stimulation of ipsilateral Zusanli (ST 36) and Yanglingquan (GB 34) acupoints for 30 min remarkably suppressed the two phases of formalin-induced spontaneous pain; 2) subcutaneous or intrathecal administration of recombinant IL-33 (rIL-33) significantly inhibited the analgesic effect of EA, whereas the ST2 antibody potentiated EA analgesia in formalin mice; 3) EA treatment decreased the up-regulation of IL-33 and ST2 protein following formalin injection; and 4) the suppression of the formalin-induced expression of spinal phosphorylated ERK and JNK induced by EA treatment was significantly attenuated following subcutaneous rIL-33 delivery, and was further decreased by the ST2 antibody. These data suggest that EA alleviates formalin-induced inflammatory pain, at least partially, by inhibiting of spinal IL-33/ST2 signaling and the downstream ERK and JNK pathways. © 2015 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | Fudan University, Sun Yat Sen University and State Key Laboratory of Medical Neurobiology
Type: | Journal: Neuroscience letters | Year: 2016

Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50A or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100A electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition.


Jiang S.,Fudan University | Xu W.,Fudan University | Xu W.,State Key Laboratory of Medical Neurobiology | Shen Y.,Fudan University | And 2 more authors.
Annals of Plastic Surgery | Year: 2012

Purpose: The optimal treatment for cubital tunnel syndrome is widely debated. The purpose of this study is to describe the technique of an endoscopic-assisted ulnar nerve decompression using carbon dioxide insufflation in association with subcutaneous anterior transposition and to assess the success or failure of the method of treatment. Methods: In all, 8 male and 4 female patients with an average age of 42 years (range, 25-56) who presented signs, symptoms, and abnormal neurophysiological studies of cubital tunnel syndrome were recruited in the retrospective study. Between August 2008 and June 2009, they were operated on using a 0-degree lens endoscope. Preoperatively, they were classified according to the Dellon scale, and the Bishop rating system was used to evaluate the postoperative outcomes. Results: Preoperatively, 5 patients were rated as mild, another 5 as moderate, and the remaining 2 as severe. The average length of the incision was 15 ± 3 mm, the mean length of the ulnar nerve decompression was 18 ± 2 cm, and the whole duration of surgery (skin to skin) lasted 30 ± 5 minutes. The endoscopic-assisted cubital tunnel release under carbon dioxide insufflation and subcutaneous anterior transposition surgeries in all patients were performed with no difficulty. All the patients had improvement in symptoms of cubital tunnel syndrome and 10 of 12 patients scored excellent according to the modified Bishop Rating System at a minimum of 1 year after surgery. Conclusions: Endoscopy-assisted cubital tunnel release under carbon dioxide insufflation demonstrated similar results compared with conventional open surgeries, besides, it may avoid problems such as long incision, painful scarring, and have additional advantages of providing an extended endoscopic view, which is safe and mini-invasive with favorable results in a 12-month follow-up. © 2012 by Lippincott Williams & Wilkins.


Zhu X.-M.,State Key Laboratory of Medical Neurobiology | Zhu X.-M.,Fudan University | Dai Y.-Q.,State Key Laboratory of Medical Neurobiology | Dai Y.-Q.,Fudan University | And 8 more authors.
Fudan University Journal of Medical Sciences | Year: 2016

To investigate the effect of caspase-3 on the proliferation of neuronal precursor cells (NPCs) in the dentate gyruse (DG) during stroke recovery. The stroke model was produced by electrocoagulating the distal middle cerebral artery (dMCA) of mice, then the NPGs were cultered from ischemia DG on the 7th day after stroke. Treatment groups and control groups were assigned in a randomized manner. The expression of caspase-3 and apoptosis and proliferation of NPCs were analyzed by Western blot, immunocytochemistry, flow cytometry analysis and TUNEL staining in NPCs cultured from ischemic DG. Besides, the effects of caspase-3 inhibition on the proliferation of NPCs in the DG was also investigated by immunohistochemistry in the mouse at 14 day after stroke. Caspase-3 was expressed in cultured NPCs, but more than 87% of the caspase-3 positive cells and TUNEL positive cells were not collocated. Caspase-3 negatively regulated self-renewal of NPCs, but did not participate in cell death in culture DG NPCs. Caspase-3 negatively regulated NPCs proliferation in the DG during stroke recovery. Caspase-3 may possess a novel function that limits the neurogenic response after stroke. © 2016, Fudan University. All right reserved.


Zhang J.,Xi'an Jiaotong University | Shi Q.,Xi'an Jiaotong University | Chen X.,Xi'an Jiaotong University | Yang P.,Xi'an Jiaotong University | And 8 more authors.
International Journal of Molecular Medicine | Year: 2012

We have previously reported that 5 copies of the hypoxia response element (HRE) can conditionally regulate brain-derived neurotrophic factor gene expression under hypoxic/ischemic conditions in mice. In the present study, we investigated the controlled expression of neurotrophin-3 (NT-3) by HRE under hypoxic conditions and determined the protective effects of conditionally expressed NT-3 on hypoxia-induced apoptosis in PC12 cells. Five copies of the HRE (5HRE) and the simian virus 40 minimal promoter (SV40mp) were employed to construct a cassette, and transfer of therapeutic gene, NT-3, into PC12 cells was achieved using a retroviral vector. Our results showed that the retroviral vector, pLNC-5HRE-NT3, was successfully constructed and transfected into PC12 cells. Compared with normal conditions, in which NT-3 was expressed at low levels, the expression of NT-3 significantly increased under hypoxic conditions in 5HRE-NT3 transgenic PC12 cells (P<0.05). By contrast, in NT-3 transgenic PC12 cells without HRE, we found no significant difference in NT-3 expression between the normoxic and hypoxic groups. The conditional adjustment of NT-3 expression by 5HRE significantly reduced apoptosis induced by hypoxia in 5HRE-NT3 transgenic PC12 cells (P<0.05) but not in 5HRE-enhanced green fluorescent protein (EGFP) transgenic PC12 cells and PC12 cells without gene transfer. In addition, the hypoxia-induced upregulation of both p38 and caspase-3 activities was suppressed in 5HRE-NT3 transgenic PC12 cells under hypoxic conditions (P<0.05). Taken together, these results demonstrate that 5HRE-SV40mp regulates NT-3 gene expression in response to hypoxia in PC12 cells. The data presented in this study may prove useful in future gene therapy studies for the treatment of ischemic diseases.


Guo Z.,Fudan University | Zhang L.,Fudan University | Wu Y.,Fudan University | Wu Y.,State Key Laboratory of Medical Neurobiology | And 7 more authors.
Brain Injury | Year: 2015

Objective: To investigate whether electro-acupuncture can serve as a method of inducing brain ischaemic tolerance (BIT) by encouraging the expression of glutamate transporter-1 (GLT-1) and suppressing the release of glutamate (Glu). Methods: Sprague-Dawley (SD) rats were divided into sham, ischaemia and EA groups. EA was performed on dazhui and baihui acupoints and the rat cerebral ischaemia model was achieved by occluding the middle cerebral artery (MCA) for 2 hours, followed by reperfusion. Dialysate was collected from the striatum in vivo to detect the concentration of Glu and the expression of Glutamate Transporter-1 (GLT-1) was examined. The changes of neurological deficit scores were evaluated at 24 hours after reperfusion, while the infarct volumes of brains were then measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Results: Compared with the ischaemia group, the concentration of Glu decreased and the expression of GLT-1 increased at most of the detective time points in the EA group; the neurological deficit scores were lower and the infarct volumes were smaller in the EA group. Conclusion: EA can up-regulate the expression of GLT-1 and inhibit the excessive release of Glu in the striatum in the process of subsequent ischaemic-reperfusion brain injury, which may be one of the mechanisms of inducing BIT and, thus, be neuroprotective for early ischaemic brain injury. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Jiang S.,Fudan University | Xu W.-D.,Fudan University | Xu W.-D.,State Key Laboratory of Medical Neurobiology | Shen Y.-D.,Fudan University | And 2 more authors.
Anatomical Science International | Year: 2011

For surgeries aimed at the dissection of full-length phrenic nerve, a full appreciation of its trajectory, blood supply and correlation with adjacent anatomical structures is necessary, especially for endoscopic manipulations. A fresh cadaver study was conducted with the purpose of avoiding surgical complications and ensuring further efficacy and efficiency of endoscopic manipulations. Ten fresh adult cadavers were dissected. Special attention was paid to the topography of the origin, the trajectory of the phrenic nerve, and its anatomic communication with the surrounding vessels and organs. In the second side of the cadavers, thoracic endoscopic manipulations and observations were also performed. The full length of the phrenic nerve was 24.6 ± 1.7 and 30.6 ± 1.8 cm on the right and left side, respectively; the blood supply of the phrenic nerve in the thoracic cavity came exclusively from the pericardiacophrenic artery; the distance between the origin of the pericardiacophrenic artery and that of the internal thoracic artery ranged from 0.5 to 5.2 cm on the right side, and from 1.4 to 5.6 cm on the left; most of the pericardiacophrenic veins intermingled with small vessels of pericardium and pleura, forming a venous network and joining the innominate vein. Endoscopic dissection of the thoracic phrenic nerve together with the accompanying pericardiacophrenic artery can be performed. Extreme attention should be paid during surgery to a section of about 6 cm in length of the artery originating from the internal thoracic artery, while the accompanying veins do not require to be spared. © 2011 Japanese Association of Anatomists.

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