Mitochondrial protective and anti-apoptotic effects of extract on hippocampal neurons in a rat model of Alzheimer's disease.

In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata (RCE) improved spatial cognition in a rat model of Alzheimer's disease. Another study from our laboratory showed that RCE enhanced neural cell proliferation in the dentate gyrus of the hippocampus and prevented damage to hippocampal neurons in a rat model of chronic stress-induced depression. However, the mechanisms underlying the neuroprotective effects of RCE are unclear.

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats.

Objectives: In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether 'Governor Vessel' (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway.

Methods: Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination.

Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord.

Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection.

Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongation in vitro and promotes nerve fiber regeneration in transected spinal cord injury.

Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co-culture system.

Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury.

Persistent neurotrophic factor delivery is crucial to create a microenvironment for cell survival and nerve regeneration in spinal cord injury (SCI). This study aimed to develop a NT-3/fibroin coated gelatin sponge scaffold (NF-GS) as a novel controlled artificial release therapy for SCI. In vitro, bone marrow-derived mesenchymal stem cells (MSCs) were planted into the NF-GS and release test showed that NF-GS was capable to generate a sustainable NT-3 release up to 28 days.

Cholera Toxin B Subunit Shows Transneuronal Tracing after Injection in an Injured Sciatic Nerve.

Cholera toxin B subunit (CTB) has been extensively used in the past for monosynaptic mapping. For decades, it was thought to lack the ability of transneuronal tracing. In order to investigate whether biotin conjugates of CTB (b-CTB) would pass through transneurons in the rat spinal cord, it was injected into the crushed left sciatic nerve.

Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection.

Introduction: Severe spinal cord injury often causes temporary or permanent damages in strength, sensation, or autonomic functions below the site of the injury. So far, there is still no effective treatment for spinal cord injury. Mesenchymal stem cells (MSCs) have been used to repair injured spinal cord as an effective strategy.

Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro.

Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats.

This study attempted to graft neurotrophin-3 (NT-3) receptor (TrkC) gene modified mesenchymal stem cells (TrkC-MSCs) into the demyelinated spinal cord and to investigate whether electroacupuncture (EA) treatment could promote NT-3 secretion in the demyelinated spinal cord as well as further enhance grafted TrkC-MSCs to differentiate into oligodendrocytes, remyelination and functional recovery. Ethidium bromide (EB) was microinjected into the spinal cord of rats at T10 to establish a demyelinated model. Six groups of animals were prepared for the experiment: the sham, PBS, MSCs, MSCs+EA, TrkC-MSCs and TrkC-MSCs+EA groups.

Graft of the gelatin sponge scaffold containing genetically-modified neural stem cells promotes cell differentiation, axon regeneration, and functional recovery in rat with spinal cord transection.

Biological materials combined with genetically-modified neural stem cells (NSCs) are candidate therapy targeting spinal cord injury (SCI). Based on our previous studies, here we performed gelatin sponge (GS) scaffold seeded with neurotrophin-3 (NT-3) and its receptor TrkC gene modifying NSCs for repairing SCI. Eight weeks later, compared with other groups, neurofilament-200 and 5-hydroxytryptamine positive nerve fibers were more in the injury site of the N+T-NSCs group.

Electroacupuncture Promotes the Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Preinduced With Neurotrophin-3 and Retinoic Acid Into Oligodendrocyte-Like Cells in Demyelinated Spinal Cord of Rats.

Transplantation of bone marrow mesenchymal stem cells (MSCs) promotes functional recovery in multiple sclerosis (MS) patients and in a murine model of MS. However, there is only a modicum of information on differentiation of grafted MSCs into oligodendrocyte-like cells in MS. The purpose of this study was to transplant neurotrophin-3 (NT-3) and retinoic acid (RA) preinduced MSCs (NR-MSCs) into a demyelinated spinal cord induced by ethidium bromide and to investigate whether EA treatment could promote NT-3 secretion in the demyelinated spinal cord.

Graft of a tissue-engineered neural scaffold serves as a promising strategy to restore myelination after rat spinal cord transection.

Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats.

The integration of NSC-derived and host neural networks after rat spinal cord transection.

Rebuilding structures that can bridge the injury gap and enable signal connection remains a challenging issue in spinal cord injury. We sought to determine if genetically enhanced expression of TrkC in neural stem cells (NSCs) and neurotrophin-3 in Schwann cells (SCs) co-cultured in a gelatin sponge scaffold could constitute a neural network, and whether it could act as a relay to rebuilt signal connection after spinal cord transection. Indeed, many NSCs in the scaffold assumed neuronal features including formation of synapses.

Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected spinal cord of rats.

Our previous study indicated that electroacupuncture (EA) could increase neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and improve functional recovery in the injured spinal cord of rats. However, the number of neuron-like cells derived from the MSCs is limited. It is known that NT-3 promotes the survival and differentiation of neurons by preferentially binding to its receptor TrkC.

Peri-sciatic administration of recombinant rat IL-1β induces mechanical allodynia by activation of src-family kinases in spinal microglia in rats.

Previous studies have shown that Interleukin-1 beta (IL-1β) is implicated in the modulation of pain sensitivity. In the present study, we found that a single peri-sciatic administration of rat recombinant IL-1β (rrIL-1β) at doses of 20 and 200 pg (100, 1000 ng/l, in 200 μl volume) induced mechanical allodynia in bilateral hindpaws in rats, lasting for about 50 days. No axonal or Schwann cell damage at the drug administration site was found following 1000 ng/l rrIL-1β administration.

Fig4 expression in the rodent nervous system and its potential role in preventing abnormal lysosomal accumulation.

The phosphatase FIG4 regulates the concentration of phosphatidylinositol 3,5-diphosphate (PI3,5P2), a molecule critical for endosomal/lysosomal membrane trafficking and neuron function. We investigated Fig4 expression in the developing CNS of mice and rats using Western blot, real-time polymerase chain reaction, and morphological techniques in situ and in vitro and after spinal cord injury. Fig4 was expressed at a high levels throughout development in myelinating cells, particularly Schwann cells, and dorsal root ganglia sensory neurons.

Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats.

Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by axonal/neuronal damage that may be caused by defective remyelination. Current therapies aim to slow the rate of degeneration, however there are no treatment options that can stop or reverse the myelin sheath damage. Bone marrow mesenchymal stem cells (MSCs) are a potential candidate for the cell implantation-targeted therapeutic strategies, but the pro-remyelination effects of MSCs when directly injected into a demyelinated cord lesion have been questioned.

Cograft of neural stem cells and schwann cells overexpressing TrkC and neurotrophin-3 respectively after rat spinal cord transection.

Effectively bridging the lesion gap is still an unmet demand for spinal cord repair. In the present study, we tested our hypothesis if cograft of Schwann cells (SCs) and neural stem cells (NSCs) with genetically enhanced expression of neurotrophin-3 (NT-3) and its high affinity receptor TrkC, respectively, could strengthen neural repair through increased NSC survival and neuronal differentiation at the epicenter after complete T10 spinal cord transection in adult rats. Transplantation of NT-3-SCs + TrkC-NSCs in Gelfoam (1 × 10(6)/implant/rat; n = 10) into the lesion gap immediately following injury results in significantly improved relay of the cortical motor evoked potential (CMEP) and cortical somatosensory evoked potential (CSEP) as well as ameliorated hindlimb deficits, relative to controls (treated with LacZ-SCs + LacZ-NSCs, NT-3-SCs + NSCs, NSCs alone, or lesion only; n = 10/group).

Transplantation of artificial neural construct partly improved spinal tissue repair and functional recovery in rats with spinal cord transection.

Delivery of cellular and/or trophic factors to the site of injury may promote neural repair or axonal regeneration and return of function after spinal cord injury. Engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic molecules. To explore therapeutic potential of engineered neural tissue, we generated an artificial neural construct in vitro, and transplanted this construct into a completely transected spinal cord of adult rats.

An experimental electro-acupuncture study in treatment of the rat demyelinated spinal cord injury induced by ethidium bromide.

Oligodendrocyte precursor cells (OPCs) are one of the potential treating tools for multiple sclerosis (MS). Therefore, the cell number and differentiation of OPCs in a demyelinated spinal cord are crucial for improvement of reparative process. In the present study, we investigated whether "Governor Vessel (GV)" electro-acupuncture (EA) could efficiently promote increase in cell number and differentiation of OPCs into oligodendrocytes, remyelination and functional recovery in the demyelinated spinal cord.

Synaptic transmission of neural stem cells seeded in 3-dimensional PLGA scaffolds.

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.

Comparative study of mesenchymal stem cells from C57BL/10 and mdx mice.

Background: Human mesenchymal stem cells (MSCs) have been studied and applied extensively because of their ability to self-renew and differentiate into various cell types. Since most human diseases models are murine, mouse MSCs should have been studied in detail. The mdx mouse - a Duchenne muscular dystrophy model - was produced by introducing a point mutation in the dystrophin gene.

[Experimental studies on the existence and distribution characteristics of neural stem cells in adult human ciliary body and retina].

Objective: To investigate the existence and distribution characteristics of neural stem cells in the eyes of adult human ciliary body and retina.

Methods: Eight eyes from 20 - 40 years old health adult and 3 infant eyes were obtained from Guangdong Eye Bank and were used in the present studies. The protein and mRNA expressions of neural progenitor cell-specific antigen nestin in the ciliary body and retina were detected by immunohistochemical staining and reverse RT-PCR assays, respectively.

Dynamical changing patterns of glycogen and enzyme histochemical activities in rat liver graft undergoing warm ischemia injury.

Aim: To investigate the changing patterns of glycogen and enzyme histochemical activities in rat liver graft under a different warm ischemia time (WIT) and to predict the tolerant time limitation of the liver graft to warm ischemia injury.

Methods: The rats were randomized into five groups, WIT was 0, 15, 30, 45, 60 min, respectively, and histochemical staining of liver graft specimens was observed. The recovery changes of glycogen and enzyme histochemistry activities were measured respectively 6 and 24 h following liver graft implantation.

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors.

Aim: To explore the dynamical changes of histology, histochemistry, energy metabolism, liver microcirculation, liver function and posttransplant survival of liver graft in rats under different warm ischemia times (WIT) and predict the maximum limitation of liver graft to warm ischemia.

Methods: According to WIT, the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60 min, respectively. The recovery changes of above-mentioned indices were observed or measured after liver transplantation.