FIGURE 2.

Status of the blood–brain barrier at three phases of cerebral edema. Cytotoxic edema is the initial step and particularly prominent in astrocytes. Cerebral ischemia and hypoxia induced the ion influx (black arrow), which leads to osmotic gradient changes. Water may flow into astrocytes in three ways, simple diffusion (thick blue double-headed arrows), passive transport through transmembrane channels (thin blue double-headed arrows), and water co-transport (blue single-headed arrows). In ionic edema, ion, and water influx are mediated by plasmalemma channels and transporters of endothelial cells. Upregulation of transporters and ion channels also occurs in astrocytes. Vasogenic edema is characterized by destruction of the BBB. The transport of ions, water, and serum proteins such as albumin and IgG may occur directly (thick gray arrow) or via pinocytic vesicles (dashed gray arrow). Multiple factors, including VEGF, MMPs, and pro-inflammatory cytokines such as TNF are involved. They mediate neuroinflammation and tight junction degradation, aggravating cerebral edema.