Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that intravenous infusion of human marrow stromal cells (hMSC) with a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA/NONOate), enhances angiogenesis, neurogenesis and neurological functional recovery after stroke in rats compared to individual therapy. Experimental groups consist of rats subjected to 2 h of middle cerebral artery occlusion (MCAo) and at 24 h after MCAo intravenous injection of (n=10/group): Group 1: phosphate buffered saline (PBS 1 ml) for control. Group 2: NONOate alone (0.4 mg/kg). Group 3: hMSCs (1 x 10(6)) alone. Group 4: hMSCs (1 x 10(6)) with NONOate (0.4 mg/kg). Functional tests and immunohistochemical staining were performed. Marginal functional recovery after treatment of stroke was found with 1 x 10(6) hMSCs alone (p=0.06) and no benefit was detected with NONOate alone (0.4 mg/kg, p=0.64). However, NONOate+hMSCs in combination significantly induced functional recovery (p<0.05). Treatment using hMSC in combination with NONOate significantly increased vessel perimeter and endothelial cell proliferation compared with hMSC or NONOate alone treatment (p<0.05). Cell proliferation and neurogenesis were assessed with bromodeoxyuridine (BrdU) labeling and immunostaining for cell type-specific markers. Combination treatment promoted increased, BrdU positive cell number in the subventricular zone (SVZ), migrating neuronal doublecortin immunoreactive cells and VEGF and bFGF expression in the ischemic boundary area compared to individual treatment. The functional therapeutic enhancement of combination treatment may be attributed to increased plasticity induced by the combination of a nitric oxide donor and hMSC therapy. These data suggest that pharmacological and cellular therapy may provide an additive therapeutic benefit after stroke.
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PMID:Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis. 1504 60

The mammalian forebrain subventricular zone (SVZ) contains stem cells capable of generating new neurons and glia. Recent studies indicate that acute brain injury is a potent stimulus for SVZ stem cell proliferation. To better understand mechanisms of the SVZ response to neonatal brain injury, we used a model that focuses on a unique mechanism of vulnerability of the immature CNS, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitotoxicity. We previously demonstrated that intracerebroventricular injection of the glutamate analog AMPA in rats at postnatal day 7 (P7) caused bilateral periventricular gray and white matter injury. We hypothesized that excitotoxic injury would stimulate cellular proliferation in the SVZ; we used the AMPA intracerebroventricular injection model to test this hypothesis. P7 rat pups received either left or right intracerebroventricular injections of S-AMPA (2.5 nmol). Normal and PBS-injected littermates were included as controls. On P8 or P14, serial coronal sections through the SVZ were collected; an immunohistochemical assay was performed with an antibody to the cell proliferation marker Ki-67. Bilateral Ki-67+ cells/SVZ were quantitated stereologically using the optical disector method. The median number of Ki-67+ cells/SVZ was increased in the SVZ of AMPA-injected rats relative to normal controls on both P8 and P14. To evaluate neurogenesis, we assayed the expression of doublecortin, a microtubular protein expressed only by immature neurons. From P8 to P14, there was a marked increase in doublecortin immunoreactive cells in the AMPA-injected SVZ. Many Ki-67+ nuclei were immediately surrounded by doublecortin staining. This study indicates that there is a proliferative response in the immature SVZ after an excitotoxic stimulus. Our findings suggest that some of these newly generated cells differentiate as immature neurons. This model may provide information about the mechanisms that regulate SVZ responses to neonatal brain injury.
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PMID:Subventricular zone proliferation after alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated neonatal brain injury. 1604 58

Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF) stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU(+)GFAP(+) NSCs to BrdU(+)DCX(+) neuroblasts in the subventricular zone (SVZ), increased BrdU(+)NeuN(+) neurons in the granular cell layer of the dentate gyrus, and increased BrdU(+)O4(+) oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS.
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PMID:Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis. 2561 Jun 50

Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic-ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells.
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PMID:Rat umbilical cord blood cells attenuate hypoxic-ischemic brain injury in neonatal rats. 2828 76

Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12-month-old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H-MRS). The results showed that N-acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg-NSC mice compared with the Tg-PBS and Tg-AD mice 10 weeks after NSCs transplantation. NSC-induced an increase in expression of synaptophysin and postsynaptic protein-95, and the number of neurons with normal synapses was significantly increased in Tg-NSC mice. More doublecortin-, BrdU/NeuN- and Nestin-positive neurons were observed in the hippocampal DG and SVZ of the Tg-NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H-MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H-MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.
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PMID:NSCs promote hippocampal neurogenesis, metabolic changes and synaptogenesis in APP/PS1 transgenic mice. 2883 33