NT-4 attenuates neuroinflammation via TrkB/PI3K/FoxO1 pathway after germinal matrix hemorrhage in neonatal rats.
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Neuroinflammation play an important role in the pathogenesis of germinal matrix hemorrhage (GMH). neurotrophin – 4 (NT- 4 ) is a member of the neurotrophin family and interact with tropomyosin receptor kinase B (TrkB ). NT- 4 has been shown to provide the following neurological effects of cerebral ischemia. We aimed to determine the function of the nerves of NT- 4 -TrkB signaling, as well as the signaling cascade downstream of phosphatidylinositol-3-kinase (PI3K) / protein kinase B (Akt) / forkhead box protein O1 (FoxO1), the following GMH in neonatal rats.
GMH induced by intraparenchymal injection of bacterial collagenase (0.3 U) in P7 rat pup. A total of 163 pups were used in this study. Recombinant Human NT- 4 is given intranasally at 1 hour after injection of collagenase. Selective TrkB ANA-12 antagonist, selective PI3K inhibitor LY29 4 002, and FoxO1 activate CRISPR given intracerebroventricularly at 2 4 hours before NT- 4 treatment to investigate the underlying mechanisms. Short-term and long-term neurobehavioral assessment, immunofluorescence staining, Nissl’s staining and Western blot performed.
The expression of phosphorylated TrkB increased after GMH, reaching peak levels on day 3 after bleeding. TrkB receptors were observed in neurons, microglia, and astrocytes. Administration rh-NT- 4 induced phosphorylation of TrkB, the expression of PI3K and Akt phosphorylation. Meanwhile, the decrease in FoxO1 and IL-6 levels. Selective inhibition of TrkB / PI3K / Akt signaling in microglia increase expression levels FoxO1 and pro-inflammatory cytokines. FoxO1 activate CRISPR increased expression of IL-6, suggesting that perhaps FoxO1 potential inducer of pro-inflammatory factors.
These results demonstrate that the PI3K / Akt / FoxO1 downstream signaling pathways may TrkB activation. Rat pups treated with rh-NT- 4 performed better than vehicle-treated animals both short-term and long-term behavioral tests. These data indicate that rh-NT – 4 reducing the expression of pro-inflammatory cytokines, improve neurological function, attenuated neuroinflammation, and thus reduced post-hemorrhagic hydrocephalus after GMH by TrkB / PI3K / Akt / FoxO1 track. These results indicate that rh-NT- 4 could be a promising therapeutic strategy for repairing nerve inflammation and hydrocephalus after GMH or other similar brain injuries.
NT-4 attenuates neuroinflammation via TrkB/PI3K/FoxO1 pathway after germinal matrix hemorrhage in neonatal rats.
Brain-derived neurotrophic factors mediate macrophage migration inhibitory factor to protect neurons against oxygen-glucose deficiency.
Macrophage migration inhibitory factor (MIF) is a chemokine that plays an important role in immune system function. Previous research suggests that MIF protect neurons under ischemic conditions. However, several studies reported on the role of MIF in nerve recovery after ischemic stroke. The purpose of this study is to identify the molecular mechanisms of neuroprotection mediated by MIF.
Description: Neurotrophin-3 Human Recombinant produced in E. coli is a non-glycosylated and non-covalently linked homodimer, containing 2x119 amino acid chains, having a total Mw of 27.2 kDa. The NT-3 is purified by proprietary chromatographic techniques.
Description: Fully biologically active when compared to standard. Determined by the dose-dependent induction of choline acetyl transferase activity in rat basal forebrain primary septal cell cultures was found to be in the range of 20-50 ng/ml, corresponding to a Specific Activity of ＞2 x 104 IU/mg.
Description: Fully biologically active when compared to standard. Determined by the dose-dependent induction of choline acetyl transferase activity in rat basal forebrain primary septal cell cultures was found to be in the range of 20-50 ng/ml, corresponding to a Specific Activity of ＞2 x 104 IU/mg.
Description: Neurotrophin-1 Human Recombinant (28-225) produced in E.Coli is a single, non-glycosylated, polypeptide chain containing 199 amino acids and having a molecular mass of 22kDa.;The NNT-1 is purified by proprietary chromatographic techniques.
Description: Neurotrophin-3 Mouse Recombinant produced in E. coli is a single, non-glycosylated polypeptide chain containing 119 amino acids and having a molecular mass of 13.6kDa. The NT-3 is purified by proprietary chromatographic techniques.
Genorise® Recombinant Equine Neurotrophin-4 protein
Human cell neuroblastoma incubated in a modified media Eagle Dulbecco under lack of oxygen-glucose (OGD) for 4 hours and then returned to the aerobic environment normal to reperfusion (OGD / R). 30 ng / mL MIF recombinant (30 ng / mL) or ISO-1 (MIF antagonist; 50 M) was administered to the Human neuroblastoma cells. Then the cell culture is assigned to one of four groups: control, OGD / R, OGD / R by MIF, OGD / R with ISO-1.
