OBJECTIVE: To compare the protective effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) during pregnancy on maternal immune activation (MIA)-induced adverse pregnancy outcomes, fetal developmental defects, and neuropsychological behavior abnormalities in offspring mice. METHODS: Eighty pregnant C57BL/6 mice were randomly divided into 5 groups: control, model, EA, TEAS, and sham-stimulation groups, 16 mice in each group. MIA models were replicated on the day 12.5 of pregnancy via tail intravenous injection with polyinosinic-polycytidylic acid. On the second day of modeling success, in the EA and TEAS groups, the interventions were delivered at bilateral "Zusanli" (ST36), with a frequency of 2 Hz, a current of 0.5 mA, and for 20 min each day in the pregnant mice; and the interventions lasted 6 days. Body mass and fertility indexes of pregnant mice, and the development indexes of offspring mice were recorded. Liquid phase suspension chip technology was used to detect the levels of cytokines and chemotactic factors in the serum of pregnant mice and and fetal brain of offspring mice. Flow cytometry was adopted to detect the proportion of the subgroups and subtypes of spleen T lymphocytes and macrophages in pregnant mice. Using the open field test, prepulse inhibition (PPI) test and Morris water maze, the spatial learning and memory were assessed in offspring mice. Immunofluorescence staining was used to detect microglial count in the medial prefrontal cortex (mPFC) in offspring mice. RESULTS: Compared with the control group, the model group showed a reduced body mass of pregnancy mice (P<0.01), smaller litter size and fewer live births (P<0.01, P<0.05), the increase in dead birth and the decrease in offspring survival rate (P<0.05, P<0.01). When compared with model group, in the EA group and the TEAS group, the body mass of pregnancy mice rose (P<0.05), litter size and live births increased (P<0.05, P<0.01), the dead birth was reduced and the offspring survival rate higher (P<0.05). In comparison with the control group, the model group showed the increase in the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), γ-interferon (IFN-γ) in the serum of pregnant mice, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the decrease in spleen M2 macrophages of pregnant mice (P<0.01); and the increase in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the model group, the EA group and the TEAS group showed the decrease in MCP-1, IL-6 and IFN-γ, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the increase in spleen M2 macrophages of pregnant mice (P<0.01, P<0.05) ; and the decrease in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the control group, in the model group, the total movement distance, escape incubation were extended (P<0.05, P<0.01), the frequency of entering the central area and crossing the platform decreased, and the activity duration in central area was shortened (P<0.05, P<0.01), the average speed rose (P<0.05), PPI%, the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance were reduced (P<0.05, P<0.01) in offspring mice. When compared with the model group, in the EA group and TEAS group, the total movement distance and escape incubation were shortened, the average speed was reduced (P<0.05), PPI% and the frequency of crossing the platform increased (P<0.05, P<0.01); the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance rose (P<0.05, P<0.01) in the offspring mice. In the EA group, the frequency of entering the central area and the activity duration in central area were higher (P<0.05, P<0.01); and in the the TEAS group, the activity duration in central area were longer (P<0.05). When compared with the control group, in the model group, microglial count in mPFC was elevated in offspring mice (P<0.05). In comparison with the model group, the EA group and the TEAS group showed the decrease of microglial count in mPFC (P<0.05). CONCLUSION EA and TEAS at "Zusanli" (ST36) during pregnancy effectively improve in the pregnancy outcomes and fetal brain developmental abnormalities induced by infection, and attenuate neurodevelopmental defects and mental disorders of offspring mice through inhibiting inflammatory activation of microglia in mPFC.
Animals ; Female ; Pregnancy ; Electroacupuncture ; Acupuncture Points ; Mice ; Mice, Inbred C57BL ; Humans ; Male

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.
Animals ; Brain ; Cytokines ; Down-Regulation ; Estrogens, Conjugated (USP) ; Graft vs Host Disease ; Injections, Intravenous ; Malaria, Cerebral ; Membrane Proteins ; Mice ; Models, Animal ; Pathology ; Plasmodium berghei ; Plasmodium ; Staphylococcal Protein A ; T-Lymphocytes