Figure 1.

Mechanism-based models of PIE. A, The mechanisms mediating epileptogenesis in the studied PIE models include the following: serum albumin (Alb) extravasation (in regions with dysfunctional BBB) → activation of astrocytic TGF-β receptors → alk5-mediated smad2/3 phosphorylation → transcriptional inflammatory changes promoting further TGF-β1 and IL-6 secretion → reorganization of the neural network → spontaneous seizures. B, A representative spontaneous seizure, as recorded in a mouse treated intraventricularly with albumin. C, Plot of the accumulating number of seizures per day in the six treatment groups demonstrates a minimum duration of 4 d as the epileptogenic period. D, Distribution of seizure onsets in the different models. dex, Dextran; B6, C57BL/6.