The purpose of this study was to investigate the effects of Rhodiola rosea extract and depression on the serotonin (5-HT) level, cell proliferation and quantity of neurons at cerebral hippocampus ofdepressive rats induced by Chronic Mild Stress (CMS). Seventy male Sprague-Dawley rats were divided into seven groups (10 per group): normal control group, untreated depressive rat model group, negative control group, positive control group, low dosage Rhodiola rosea extract (1.5g/kg) group, medium dosage Rhodiola rosea extract (3g/kg) group and high dosage Rhodiola rosea extract (6g/kg) group. After the depressive rats induced by CMS had received Rhodiola rosea extract for 3 weeks, the 5-HT levels at cerebral hippocampus were detected by high performance liquid chromatography. Bromodeoxyuridine (BrdU) was injected in vivo to label the proliferating cells at hippocampus, and morphometry was used to count the hippocampal neurons. The results showed that the 5-HT level of the three experimental groups had recovered to normal status. The immunohistochemistry of hippocampus BrdU positive cells had returned to the normal level in the group of depressive rats with low dosage Rhodiola rosea extract. In conclusion the results demonstrated that Rhodiola rosea extract could improve 5-HT level in hippocampus in depressive rats, and low dosage Rhodiola rosea could induce neural stem cell proliferation at hippocampus to return to normal level, repairing the injured neurons at hippocampus.

Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools fortreatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injuredspinal cord still need to be improved. In the present study, we investigated whether Governor Vesselelectro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs)survival and differentiation, axonal regeneration and finally, functional recovery in the transectedspinal cord.

To explore therapeutic potential of engineered neural tissue, we combined genetically modified neural stem cells (NSCs) and poly(lactic acid-co-glycolic acid) (PLGA) polymers to generate an artificial neural network in vitro. NSCs transfected with either NT-3 or its receptor TrkC gene were seeded into PLGA scaffold. The NSCs were widely distributed and viable in the scaffold after culturing for 14 days. Immunoreactivity against Map2 was detected in >70% of these grafted cells, suggesting a high rate of differentiation toward neurons. Immunostaining of synapsin-I and PSD95 revealed formation of synaptic structures, which was also observed under electron microscope. Furthermore, using FM1-43 dynamic imaging, synapses in these differentiated neurons were found to be excitable and capable of releasing synaptic vesicles. Taken together, our artificial PLGA construct permits NSCs to differentiate toward neurons, establish connections and exhibit synaptic activities. These findings provide a biological basis for future application or transplantation of this artificial construct in neural repair

Skin-derived precursors (SKPs) are derived from mesoblast and can differentiate into smooth muscle cells, adipocytes, and less neuronal phenotypes. This study demonstrates that retinoic acid (RA) improves SKPs exit from self-proliferation to neural differentiation through up-regulating of NeuroD andcell-cycle regulatory protein p21, meanwhile RA also induces p75 neurotrophin receptor (p75NTR) upregulation and apoptosis of SKPs. When treated sequentially with neurotrophin-3 (NT-3) after RA induction, the survival and neural differentiation of SKPs were enhanced significantly, and cell apoptosis induced by RA was decreased. These effects could be reversed by p75NTR inhibitor Pep5 instead of Trk receptor inhibitor K252a. The results indicate that NT-3 improves the neural differentiation of SKPs induced by RA through a p75NTR-dependent signaling pathway

This study investigated whether electro-acupuncture (EA) would improvethe survival and migration of neural stem cells (NSCs) transplanted ininjured spinal cord as well as the potential mechanisms. TlO spinal cordsegments of 50 adult Sprague-Dawley (SD) rats were completely transected,and then NSCs were immediately transplanted into the transected site of theexperimental animals, while control animals were sham operated withouttransplantation. Five days post-operation, electro-acupuncture treatment onGV9 (Zhiyang), GV6 (Jizhong), GV2 (Yaoshu) and GVI (Changqiang)acupoints was applied for 14 days (EA+NSCs 14d) and 30 days (EA+NSCs30d). ELISA and immunohistochemical staining were used to assess thecontent of neurotrophine-3 (NT-3) and the characteristics of transplantedNSCs. We found that the number of transplanted NSCs the survived inEA+NSCs14d group was significantly increased as compared to that of theNSCs30d group (5825.20+819.01vs 4781.40+500.49, P<0.05).19Immunostaining indicated that some transplanted NSCs developed intomicrotubule association protein 2 (MAP2) positive cells and many of themdeveloped into glial fibrillary acidic protein (GFAP) positive cells in theNSCs30d group. Further, the migration length of transplanted NSCs towardcaudal tissue in the injured site was longer in the EA+NSCs30d group thanthat in NSCs30d group (5.98+0.79mm vs 3.96+1.72mm; P<0.05). AlsoNT-3 in injured spinal cord tissue was 23% increased in the EA+NSCs14dgroup. These results suggest that the combination of EA and NSCs improvesthe survival and migration of NSCs in injured spinal cord in rats.

Spinal cord transection results in severe neurological sequelae, and to date, there is no effective treatment. Because of the limited capacity for axonal regeneration in the spinal cord, recovery is minimal. Recently, efforts have been made to establish, by grafting neural tissue, a functional relay-station between the severed stumps of the injured cord. Previously, we used co-transplantation of neural stem cells (NSCs) and Schwann cells (SCs) to improve functional recovery of transected spinal cord. However, this effort has been partially impeded by limited neuronal differentiation of transplanted NSCs. To circumvent this problem, we have pre-differentiated NSCs toward neurons in vitro with the application of retinoic acid (RA) prior to cell grafting. Further, we genetically modifiedSCs to overexpress human neurotrophin-3 (hNT-3). When these cells were co-transplanted into the transected spinal cord of rats, injured animals had partial improvement (both functionally and structurally), including improved Basso, Beattie, and Bresnahan (BBB) scores, increased axonal regeneration/remyelination, and reduced neuronal loss. However, this pre-differentiation of NSCs in vitro only mildly improved neuronal differentiation of NSCs in vivo.

Cyclosporine is one of the foremost immunosuppressive agents for cell, tissue, and organ transplantation. Cyclosporine is, however, associatedwith signicant side e

The present study investigated whether morphine can promote regeneration and synaptic reconstruction of the terminals of injured primary afferent fibers in lamina II of the spinal cord in rats following sciatic nerve injury. Fluoride-resistant acid phosphatase (FRAP)- positive terminals in lamina II of the L4 spinal segment after sciatic nerve injury were assessed after treatment with vehicle, morphine, and naloxone plus morphine. Under the electron microscope, types I and II complex terminals of unmyelinated afferent fibers from the dorsal root, simple terminals of interneuronal axons, and terminals of descending axons at lamina II of the L4 spinal segment were documented in the different groups after injury. FRAP-positive terminals in lamina II were depleted after sciatic nerve injury in the vehicle group. Treatment with morphine increased the numbers of FRAP-positive terminals, and this was prevented by naloxone. The present study demonstrates that morphine may promote the regeneration and synaptic reconstruction of the terminals of injured primary unmyelinated afferent fibers in lamina II of spinal cord, by a process mediated by μ-opioid receptors.

An animal model oftransected spinal cord injury (SCI) was used to test thehypothesis that cografted neural stem cells (NSCs) and NT-3-SCs promote morphologic andfunctional recoveries of injured spinal cord.Objective: To explore whether cotransplant ofNSC s and NT-3-SCs could promote the injured spinal cord repair. Setting: Zhongshan Medical College, Sun Yat-sen University, PR China. Methods: Female Sprague-Dawley (SD) rats weighing on 200-220g were used to prepare SCI models. The spinal cord was transected between T9 and T10, then NSCs, SCs

AbstractWe have constructed a recombinant adenovirus expression vector carrying the human neurotrophin-3 (NT-3) receptor TrkC (tyrosine proteinkinase C) gene (rAd-TrkC; 2478 bp) and confirmed the expression of the encoded TrkC in green fluorescent protein (GFP)-murine neural stem cells (NSCs) by reverse transcription polymerase chain reaction (RT-PCR),Western blot analysis, andimmunocytochemistry. The activity of the expressedrAd-TrkC was verified in vitro by evaluating dose-related responses of NSCs to NT-3, a TrkC specific ligand. TrkC-GFP-NSCs had a significantly higher percentage of neuronal differentiation when treated with NT-3 relative to the rAd-LacZ control cells (55.2% vs. 29.8%; P<0.05, χ2 test).Thus, our rAd-TrkC vector can transfect NSCs and produce functional TrkC receptors to promote neuronal differentiation of NSCs.