Thrombin effects at low and high doses. At low doses, astrocytes lose their star morphology maintain their fundamental role in nutrient supply, glutamate (Glu) sinking, and glutathione (GSH) production, thus promoting cell survival and synaptic plasticity; the blood–brain barrier (BBB) and extracellular matrix (ECM) both maintain their stability. At high doses, reactive astrocytes and microglia proliferate, lose their Glu regulatory function, and produce reactive oxygen species (ROS) and inflammatory cytokines (interleukin 1β (IL-1β), tumor necrosis factor α (TNFα)); neurons suffer neurite retraction, intracellular Ca2+ upregulation, and finally cell death, while the BBB is damaged and the ECM is digested by matrix metalloproteinases (MMPs).