THBS1 and Dravet syndrome: Here, we show that: 1) DS astrocytes play a significant role in spine pathology and reduced synaptic density; 2) both DS brains and DS astrocytes show deficits in TSP-1 levels and secretion; 3) TSP-1 modulates dendritic spine development and morphology; and 4) TSP-1 addition reverts DS astrocyte-mediated spine and synaptic alterations.