In mice, Sampah et al. and Nino et al. showed the onset of NEC in the intestine leads to excessive TLR4 signaling and activation of an endogenous ligand HGMB1 (high mobility group box 1) which enters the systemic circulation and activates TLR4 receptors on microglia in the brain. This evidence concerns the gene TLR4 and necrotizing enterocolitis.