000K utf8 1100 2020$c2020-10-06 1500 eng 2050 urn:nbn:de:hbz:464-20210125-121311-8 2051 10.3389/fneur.2020.540878 3000 Serdar, Meray 3010 Bendix, Ivo 3010 Felderhoff-Müser, Ursula 3010 Herrmann, Ralf 3010 Herz, Josephine 3010 Kempe, Karina 3010 Picard, Daniel 3010 Remke, Marc 3010 Sabir, Hemmen 4000 Involvement of CXCL1/CXCR2 During Microglia Activation Following Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats [Serdar, Meray] 4209 Background: Microglia are key mediators of inflammation during perinatal brain injury. As shown experimentally after inflammation-sensitized hypoxic ischemic (HI) brain injury, microglia are activated into a pro-inflammatory status 24 h after HI involving the NLRP3 inflammasome pathway. The chemokine (C-X-C motif) ligand 1 (CXCL1), and its cognate receptor, CXCR2, have been shown to be involved in NLRP3 activation, although their specific role during perinatal brain injury remains unclear. In this study we investigated the involvement of CXCL1/CXCR2 in brain tissue and microglia and brain tissue after inflammation-sensitized HI brain injury of newborn rats. Methods: Seven-day old Wistar rat pups were either injected with vehicle (NaCl 0.9%) or E. coli lipopolysaccharide (LPS), followed by left carotid ligation combined with global hypoxia (8% O2 for 50 min). Pups were randomized into four different treatment groups: (1) Sham group (n = 21), (2) LPS only group (n = 20), (3) Veh/HI group (n = 39), and (4) LPS/HI group (n = 42). Twenty-four hours post hypoxia transcriptome and gene expression analysis were performed on ex vivo isolated microglia cells in our model. Additionally protein expression was analyzed in different brain regions at the same time point. Results: Transcriptome analyses showed a significant microglial upregulation of the chemokine CXCL1 and its receptor CXCR2 in the LPS/HI group compared with the other groups. Gene expression analysis showed a significant upregulation of CXCL1 and NLRP3 in microglia cells after inflammation-sensitized hypoxic-ischemic brain injury. Additionally, protein expression of CXCL1 was significantly upregulated in cortex of male pups from the LPS/HI group. Conclusion: These results indicate that the CXCL1/CXCR2 pathway may be involved during pro-inflammatory microglia activation following inflammation-sensitized hypoxic-ischemic brain injury in neonatal rats. This may lead to new treatment options altering CXCR2 activation early after HI brain injury. 4950 https://doi.org/10.3389/fneur.2020.540878$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:hbz:464-20210125-121311-8$xR$3Volltext$534 4961 https://duepublico2.uni-due.de/receive/duepublico_mods_00073425 5051 610 5550 brain 5550 chemokine 5550 HIE 5550 infection 5550 inflammation 5550 microglia 5550 newborn