Fig. 6

Integrated results of this study to diagrammatically show how LPS-induced systemic inflammation facilitates the onset of cerebral edema under short-term hypoxia in rats by (1) LPS-induced pro-inflammatory pathway which activates AQP4 and contributes to water permeability of astrocytes via TLR4 signaling MAPKs and NF-κB, (2) short-term hypobaric hypoxia which reduced Na⁺-K⁺-ATPase activity resulting in water inflow in astrocytes, (3) LPS + hypoxia-induced leakage of BBB resulting in vasogenic edema. All together, these factors contribute to brain edema. Under prolonged hypoxia, systemic inflammation may worsen the cerebral edema by (1) LPS plus hypoxia-induced astrocyte cytotoxic swelling; (2) LPS plus hypoxia-activated cortical microglia release of cytokines, which further stimulate astrocyte swelling; and (3) hypoxia further reducing Na⁺-K⁺-ATPase activity, and LPS + hypoxia triggering leakage of BBB. This mechanism in rats may describe the onset and deterioration of HACE in human