Figure 1.

Possible mechanisms involved in brain protection or swelling after metal-ion intoxication. After crossing the blood-brain barrier metal-ions are taken up by astrocytes. Fe⁺², Mn⁺², Pb⁺² increase water permeability throughout aquaporin-4 (AQP4), leading to cell swelling and glutamate release from astrocytes by volume-regulated anion channels (VRACs), increasing extracellular glutamate pool. Glutamate acts via NMDA receptor in neurons and astrocytes, increasing [${\text{Ca}}_{\text{i}}^{+2}$] and reactive oxygen species (ROS) production, generating oxidative stress. Methylmercury (MeHg) reduces cystein uptake, increasing ROS production. Oxidative stress leads to increase in AQP4 and AQP9 in astrocytes, which leads to cell swelling.