Abstract
BackgroundWhite matter injury (WMI) induced by intrauterine inflammation can cause adverse neurological outcomes. Fibrinogen-like protein 2 (FGL2)/fibroleukin is an important trigger of inflammatory responses and is involved in some cerebral diseases. However, the role of FGL2 in intrauterine inflammation-induced WMI remains unclear.MethodsLipopolysaccharide (LPS) was intraperitoneally injected into wild-type and FGL2 knockout mice to induce intrauterine inflammation. Body weight and brain weight of offspring were monitored. Major basic protein (MBP) expression was evaluated to demonstrate the myelination of offspring. To investigate the regulatory mechanism of FGL2, cytokine expression, microglial polarization, and the activation of mitogen-activated protein kinase (MAPK) signaling pathway in the offspring were analyzed.ResultsUpon LPS exposure, FGL2 knockout offspring showed a significant increase in body weight loss. MBP reduction induced by LPS was prevented in FGL2 knockout offspring. Expression levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α, and M1 marker CD86 were suppressed, while the expression levels of anti-inflammatory cytokines IL-10 and M2 marker CD206 were increased. FGL2 deficiency significantly inhibited the phosphorylation of p38MAPK and c-Jun N-terminal kinase (JNK) protein.ConclusionsFGL2 deficiency can ameliorate WMI induced by intrauterine inflammation, reducing inflammatory cascade and improving hypomyelination, through the regulation of microglial polarization and MAPK signaling pathways.ImpactIntrauterine inflammation induces WMI leading to severe neurological sequelae. FGL2 plays an important role in the progression of WMI induced by intrauterine inflammation.FGL2 deficiency can protect against WMI by inhibiting p38 MAPK and JNK phosphorylation, regulating microglia polarization, and reducing inflammation response.FGL2 could be a novel molecular target for protecting against WMI induced by intrauterine inflammation.
Highlights
White matter injury (WMI) is a common form of immature brain injury, and one of the leading causes of long-term neurological deficits, such as cognitive deficit, mental retardation, and even cerebral palsy (CP)
KO of Fibrinogen-like protein 2 (FGL2) protects against body weight loss induces by intrauterine inflammation To obtain surviving pups, dams were intraperitoneally injected with 300 μg/kg LPS on E16.5
On postnatal day 1 (P1), the body weight of LPStreated WT mice was significantly lower than saline-treated WT mice (P = 0.029), while FGL2 KO mice were resistant to body weight changes caused by LPS (P = 0.019)
Summary
White matter injury (WMI) is a common form of immature brain injury, and one of the leading causes of long-term neurological deficits, such as cognitive deficit, mental retardation, and even cerebral palsy (CP). Intrauterine inflammation can cause inflammatory response, ischemia–hypoxia, and oxidative stress, and so on, leading to WMI.[5] Cytokine is one of the strong link factors in the inflammatory response. White matter injury (WMI) induced by intrauterine inflammation can cause adverse neurological outcomes. METHODS: Lipopolysaccharide (LPS) was intraperitoneally injected into wild-type and FGL2 knockout mice to induce intrauterine inflammation. To investigate the regulatory mechanism of FGL2, cytokine expression, microglial polarization, and the activation of mitogen-activated protein kinase (MAPK) signaling pathway in the offspring were analyzed. CONCLUSIONS: FGL2 deficiency can ameliorate WMI induced by intrauterine inflammation, reducing inflammatory cascade and improving hypomyelination, through the regulation of microglial polarization and MAPK signaling pathways
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
