Therapeutic effect of erythropoietin on brain injury in premature mice with intrauterine infection

Abstract

Objective The objective of this study is to explore the protective effect of erythropoietin (EPO) on brain injury induced by intrauterine infection in premature infants and its related mechanism, so as to provide reference for clinical medication. Methods Intrauterine infection model is established by injecting lipopolysaccharide into pregnant mice, and HE staining of mouse placenta is used to judge whether the model of intrauterine infection is successful or not. Fifteen female rats are successfully pregnant and divided into intrauterine infection group (10 rats) and control group (5 rats). The mice in the intrauterine infection group are intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 0.3 mg/kg. After delivery, 16 newborn mice in the control group are randomly selected as blank control group. 32 newborn mice in the intrauterine infection group are selected as model group, and then divided into infection group and EPO treatment group, 16 mice in each group. After birth, mice in the blank control group are intraperitoneally injected with 0.2 mL saline daily. The infected mice are intraperitoneally injected with 0.2 mL saline daily. The mice in the EPO treatment group are intraperitoneally injected with recombinant human erythropoietin (rhEPO) 5000 IU/kg daily. HE staining results, EPOR protein and NMDAR1 mRNA expression in brain tissue of three groups of neonatal mice were compared. Results Firstly, the blood vessels of the mice in the intrauterine infection group are markedly hyperemic and edematous, and the infiltration of neutrophils is increased. The white matter structure of the neonatal mice in the intrauterine infection group is loose and stained lightly. The nerve fibers in the brain are different in thickness and disordered in arrangement. The nucleus is small and dark stained. The number of glial cells in brain tissue increases significantly. Secondly, the EPOR protein expression and physiological level of neonatal mice in intrauterine infection group increase significantly at 3, 7 and 14 days after birth. Compared with the blank control group, the difference is statistically significant (P < 0.05). On the 3rd day after birth, the expression level of EPOR protein in the EPO treated group is significantly higher than that in the intrauterine infection group (P < 0.05). Thirdly, the expression level of NMDA R1mRNA in brain tissue of neonatal mice at birth, on the 3rd and 7th day after EPO treatment is significantly lower than that of intrauterine infection group (P < 0.05). Conclusion EPO can promote the proliferation and differentiation of brain endogenous neural stem cells, and has a certain therapeutic effect on brain injury of premature mice caused by intrauterine infection.

Angiogenic responses are enhanced by recombinant human erythropoietin in a model of periventricular white matter damage of neonatal rats through EPOR-ERK1 signaling

“…Administration of high doses of EPO facilitated EPO/EPOR signaling, leading to the promotion of new CA1 neurons and dendritic spine density. In a study involving premature infants, the EPO-treated group exhibited significantly higher levels of EPOR protein expression compared to the control group in the presence of brain damage ( 15 ). Therefore, we hypothesized that the initiation of EPO signaling occurs subsequent to the establishment of the EPO/EPOR complex on the cellular membrane, thereby instigating the activation of subsequent signal transduction pathways.…”

“…EPO inhibits inflammation, excitotoxicity, oxidative stress, and apoptosis in neurons and oligodendroglia ( 11–13 ), indicating the neuroprotective potential of treatment of premature infants with a recombinant human erythropoietin (rh-EPO). rh-EPO promotes neurogenesis and angiogenesis, both of which are essential for repairing brain damage and developing compensatory mechanisms that promote neurodevelopment ( 14 , 15 ). In newborn infants, rh-EPO has been evaluated for its ability to protect neurons ( 16 , 17 ).…”

Anemia status of infants and young children aged six to thirty-six months in Ma'anshan City: A retrospective study

“…This trend could be attributed to the fluctuations in hormone levels and growth factors inherent to child development. Specifically, erythropoietin - a hormone instrumental in fostering the production and maturation of red blood cells - might experience variations in its secretion levels as children grow, subsequently influencing hemoglobin concentrations[ 20 , 21 ]. The period from 9 to 36 mo is when children experience the fastest growth, tripling their size at birth[ 22 ], indicating an increased need for iron[ 23 , 24 ].…”

Recombinant human erythropoietin upregulates PPARγ through the PI3K/Akt pathway to protect neurons in rats subjected to oxidative stress

“…Second, in this oxidative stress rat model, the apoptosis rate of hippocampal neurons after the rhEPO intervention was only approximately 5%, which was significantly lower than the 25% apoptosis rate of neurons cultured in vitro in the presence of rhEPO (Wang et al, 2017). We speculated that the protective effect of rhEPO on the nervous system of rats subjected to oxidative stress may not only be limited to neurons but may also extend to glial cells, thereby reducing neuron apoptosis through the action of glial cells (Anagnostou et al, 2018; Liu et al, 2020). At the same time, rhEPO may act on the central nervous system to induce the production of other endogenous neuroprotective factors, such as BDNF (Esmaeili Tazangi et al, 2015; Jia et al, 2016), thereby amplifying its protective effect and reducing cell apoptosis.…”