Analysis of gene expression profiles associated with functional recovery after spinal cord injury caused by sema4D knockdown in oligodendrocytes.

We previously showed that sema4D Knockdown in oligodendrocytes promotes functional recovery after spinal cord injury. In this paper, we examined gene expression profiles associated with functional recovery by PCR array. For general observation during first 4 weeks, we found that sema4D knockdown could reduce edema and stimulate SCEP. Further, PCR array analysis indicated sema4D knockdown in OPCs inhibited wound tissue angiogenesis and inflammation genes expression and upregulated axon regeneration genes expression at early phase. Our findings provided the molecular mechanism for its potential application.

Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro.

Bone marrow mesenchymal stem cells (MSCs) transplantation has shown great promises for treating various central nervous system (CNS) diseases. However, poor viability of transplanted MSCs in injured CNS has limited the therapeutic efficiency. Oxidative stress is one of major mechanisms underlying the pathogenesis of CNS diseases and has a negative impact on the survival of transplanted MSCs. Melatonin has recently been reported to have the antioxidant and anti-apoptotic properties in serial of cells. This study was designed to investigate the protective effect and potential mechanisms of melatonin against hydrogen peroxide (H2O2)-induced apoptosis of MSCs. MSCs were pretreated with melatonin (1, 10, and 100 nM, respectively) for 30 min, followed by exposure to 400 µM H2O2 and melatonin together for 12 h. The present study reports that melatonin pretreatment significantly attenuated H2O2-induced MSC apoptosis in a dose-dependent manner. Consistently, melatonin effectively suppressed the generation of intracellular ROS, expression ratio of Bax/Bcl-2, activation of caspase-3 and expression of phospho-P38MAPK in H2O2-induced MSCs. Luzindole, a nonselective melatonin receptor antagonist, significantly counteracted melatonin's promotion effect on cell survival, indicating that melatonin exerts its protective effect on MSCs, at least in part, through the activation of melatonin receptors. The findings suggest that melatonin may be an effectively protective agent against oxidative stress-induced MSC apoptosis.

Microglia--friend or foe.

Microglia, as the immune effectors in the central nervous system, respond to pathological conditions and participate in the initiation and progression of neurological disorders such as inflammation and brain tumor by releasing potential neurotrophic or cytotoxic molecules, presenting the antigen to T cell and interacting with brain tumor. Evidences also suggest that microglia are capable of promoting or inhibiting the proliferation and differentiation of neural stem cells by secreting series of biologically active molecules. In this review, we focus on three aspects-inflammation, neurogensis and brain tumor to illustrate the multi-faceted activities of microglia in the normal and pathologic brain.

Roles of activated astrocyte in neural stem cell proliferation and differentiation.

Recent studies demonstrated that the molecules secreted from astrocytes play important roles in the cell fate determination of neural stem cells (NSCs). However, the exact molecules involved and its possible mechanisms in the process remain largely unknown. In this study, astrocyte-conditioned medium (ACM) obtained from astrocytes unstimulated or stimulated by lipopolysaccharide was prepared to treat NSCs. The results showed that both the proliferation and differentiation of NSCs treated with stimulated ACMs were significantly increased compared with those treated with unstimulated ACM. Interleukin-6 (IL-6) antibody neutralization of the ACMs decreased NSC proliferation and astrogliogenesis, while NSC neurogenesis was increased. In contrast, recombinant IL-6 cytokine increased NSC proliferation and astrogliogenesis, but decreased neurogenesis. Furthermore, the expression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) protein as well as serial of basic helix-loop-helix transcription factors (bHLH) mRNA in NSCs exposed to stimulated ACMs significantly increased, respectively. The expression levels of p-stat3 protein and bHLH mRNA of NSCs were significantly altered after adding anti-IL-6 antibody or recombinant IL-6, respectively. The data suggest that IL-6 secreted from activated astrocytes participates in ACM-induced proliferation and differentiation of NSCs via the phosphorylation of stat3 signals and the expression of bHLH transcription factors.

c-Abl is involved in high glucose-induced apoptosis in embryonic E12.5 cortical neural progenitor cells from the mouse brain.

Hyperglycemia causes direct apoptosis of neural progenitor cells (NPCs) in diabetic-induced neural tube defects in embryos. However, the underlying mechanisms are poorly understood. The present study is aimed to investigate the specific cellular proteins that may be involved in NPCs apoptosis as well as mechanisms by which the proteins regulate the oxidative stress-induced NPCs apoptosis. Our present results have shown that the expression of c-Abl was up-regulated in NPCs exposed to high glucose in vitro. The increased c-Abl was localized mainly in the nucleus. High glucose also induced an increase in nuclear p53 protein levels and the p53-c-Abl complex in NPCs. Administration of reactive oxygen species scavengers decreased the protein level of c-Abl, p53 and NPCs apoptosis. Inhibition of c-Abl reduced NPCs apoptosis and the nuclear protein level of p53 in response to high glucose. These results demonstrate that c-Abl is involved in the reactive oxygen species-activated apoptotic pathways in NPCs apoptosis. Inhibition of c-Abl may protect NPCs against insults induced by high glucose via the modulation of NPCs apoptotic machinery.

Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose.

Folic acid (FA) supplementation has been shown to be extremely effective in reducing the occurrence of neural tube defects (NTDs), one of the most common birth defects associated with diabetic pregnancy. However, the antiteratogenic mechanism of FA in diabetes-induced NTDs is unclear. This study investigated the neuroprotective mechanism of FA in neural stem cells (NSCs) exposed to high glucose in vitro. The undifferentiated or differentiated NSCs were cultured in normal D-glucose concentration (NG) or high D-glucose concentration (HG) with or without FA. FA supplementation significantly decreased apoptosis induced by HG and lowered the expression of p53 in the nucleus of undifferentiated NSCs exposed to HG. Administration of FA in differentiated NSCs did not alter their precocious differentiation induced by HG. The increased mRNA expression levels of the basic helix-loop-helix factors including Neurog1, Neurog2, NeuroD2, Mash1, Id1, Id2, and Hes5 in the presence of HG were not significantly affected by FA. The present results provided a cellular mechanism by which FA supplementation may have a potential role in prevention of NTDs in diabetic pregnancies. On the other hand, FA increased the mRNA expression levels of the above transcription factors and accelerated the differentiation of NSCs in the NG medium, suggesting that it may adversely affect the normal differentiation of NSCs. Therefore, the timing and dose of FA would be critical factors in considering FA supplementation in normal maternal pregnancy.

Effects of scutellarin on apoptosis induced by cobalt chloride in PC12 cells.

The present study investigated the protective effects of scutellarin on cobalt chloride (CoCl2)-induced apoptosis in PC12 cells. Incubation of PC12 cells with 500 microM CoCl2 for 24 h resulted in significant apoptosis as evaluated by the crystal violet, electron microscopy and flow cytometry assays. The increase of caspase-3 activity, decrease of Bcl-XL expression, phosphorylation of p38 mitogen-activated protein kinase (MAPK) and accumulation of intracellular reactive oxygen species (ROS) were also seen in CoCl2-treated PC12 cells. Scutellarin at 0.1, 1 and 10 microM significantly protected against the apoptotic cell death induced by CoCl2. Scutellarin decreased caspase-3 activity, increased Bcl-XL expression, inhibited p38 phosphorylation and attenuated ROS production. These results demonstrate that scutellarin can protect PC12 cells from cobalt chloride induced apoptosis by scavenging ROS, inhibiting p38 phosphorylation, up-regulating Bcl-XL expression and decreasing caspase-3 activity, and may reduce the cellular damage in pathological conditions associated with hypoxia-mediated neuronal injury.