Figure 5.

Mechanisms involved in epileptogenesis triggered by the blood–brain barrier (BBB) permeability changes. Brain influx of serum proteins at sites of the BBB disruption, in particular that of albumin and thrombin, trigger profound astrocytic responses. Astrocytes internalize albumin via transforming growth factor (TGF)β receptors and this process triggers calcium-dependent signaling, leading to transcriptional changes; as a result, potassium inward rectifier, Kir4.1, and glutamate transporters are downregulated, whereas cytokines are upregulated and released by astrocytes. Consequently, synaptic buffering of potassium and glutamate is reduced, leading to increased excitability during neuronal activity and changed neuronal network responses leading to epileptogenesis.