Granulocyte Colony-stimulating Factor Ameliorates Periventricular White Matter Damage Subject To Hypoxia Via Influencing On Activation Of Microglia

Granulocyte colony-stimulating factor (G-CSF) is a kind of hematopoietic growth factors that induces progenitor cells differentiate into neutrophil. As the treatment of congenital neutropenia, neutropenia caused by infection control after chemotherapy drug, G-CSF has been put into the clinical application for two decades. The clinical study shows that G-CSF is a kind of safe and effective drug with little side effect. Recent research suggests that G-CSF may be anti-inflammatory, anti-apoptotic, induce the regeneration of nerves and blood vessels, thus contributing to the restoration of the structure and function of the nervous tissue, nutritious for nerve cells, nerve injury protection, but the specific mechanism of its neuroprotective function is not clear yet.The latest research found that when the rodent central nervous system suffer by ischemia-reperfusion injury, nerve cells upregulate the quantity of granulocyte colony-stimulating factor receptor(G-CSFR) and increase G-CSF secretion. Global study shows that, in the various stages of development in the rat central nervous system, G-CSF and G-CSFR expression of unequa distribution in the various regions, and expressed in microglia, especially. This suggests that G-CSF may have a repair function in nerve injury. We guess, this feature can be played by affecting the microglial cells. This will also provides a theoretical basis for G-CSF as a neuroprotective drug in the treatment of the disease of the nerve injury.Periventricular white matter damage (PWMD) is premature children brain damage the most important pathological types, including the periventricular white matter softening periventricular white matter area bleeding and infarction, and late ventricle dilatation, is the impact of life after birth Quality is the most important factor. A large number of microglia in the periventricular white matter development, distribution, and plays a vital role in the PWMD. When the central nervous system suffered damage stimulus, as the innate immune cells present in the central nervous system, microglia are rapidly activated and play a dual role. On the one hand, activated microglia play a neuroprotective effect. On the other hand, injury and a variety of inflammatory cytokines stimulate the microglia release cytotoxic substances, then cause neurological dysfunction, neurons and oligodendrocytes, glial cells and other cell death, further aggravating the damage to the body. According to the the genotyping theory proposed by Gordon S, activated macrophages can be divided into classical activation (M1type) and select activated (M2type), two types of cells have distinct immunological phenotypes, and the functions they play are also very different M1-type cells by secreting cytokines promote inflammation, and anti-tumor effect. M2-type inhibition of inflammation, promote tissue regeneration and repair. The study observes that G-CSF changes the number and proportion of the M1-type cells and M2cells to produce the protective effect against hypoxia causes PWMD, and explore its role of mechanism.1.G-CSF affects early and long-term neurobehavioral function recovery as well as abnormal brain development due to hypoxia1d-old mice placed in a hypoxic chamber pass into5%02and95%N2gas to be inside until the proportion of gas is stable. Hypoxia time is2h. Treatment group to intraperitoneal injection of recombinant human granulocyte colony-stimulating factor in the periventricular white matter injury in animal models before manufacturing2h,2h after the end of the model, the treatment group was administered once again. Administered once a day, after continuous7d.5days and10days after the birth of the mice, they are put into plane righting experiments after8,10,12days we start a swimming test,and after30,31,32days we do a open-field test.The results showed that G-CSF can promote recovery of eary and long-term function of brain in mice, ameliorate neurodevelopmental abnormalities due to injury and improved neurobehavioral defects.2. G-CSF affects raising, activation of microglia, and the secretion of microglia in periventricular white matter1,3and7days after modeling, we take brain slices and do double immunofluorescence to detect microglia raised to the periventricular white matter as well as inflammatory cytokine secretion of microglia. We take periventricular white matter, using the enzyme-linked immunosorbent assay (ELISA) to detect the level of secretion of inflammatory cytokines. The number and proportion of the two types of activated microglia change and the secretion of proinflammatory cytokines and anti-inflammatory cytokines was detected by RT-PCR.The results show that, G-CSF increase microglia raised to the periventricular white matter, activate microglia, and change the number and proportion of cells activated microglia Ml and M2-type cells. Reduce microglial proinflammatory cytokine secretion, and increase the secretion of anti-inflammatory cytokines and neurotrophic factors.In short, through this study, we find that the use of G-CSF in P WMD intervention can be anti-inflammatory, and microglia can induce transformation towards neuroprotective regulating. G-CSF decreases the secretion of inflammatory factors and increases neurotrophic factors. At the same time, it promotes the recovery of motor function after injury.