Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that is among 
the most common genetic causes of epilepsy. Focal brain lesions in TSC, known as 
cortical tubers, have been implicated in promoting epileptogenesis in TSC. 
Histological, cellular, and molecular abnormalities in astrocytes are 
characteristic features of tubers and perituberal cortex, suggesting that 
astrocyte dysfunction may contribute to the pathophysiology of epilepsy in TSC. 
Numerous astrocytes can be seen histologically in tubers expressing glial 
fibrillary acidic and S100 proteins. In some analyses, astrocytes exhibit 
enhanced activation of the mammalian target of rapamycin suggesting a link 
between TSC1 and TSC2 mutations and astrocytic proliferation. Astrocytic 
proliferation in subependymal giant cell astrocytoma is associated with 
progressive growth and compression of surrounding brain structures by these 
lesions. Increased numbers of enlarged astrocytes has been observed in several 
TSC mouse models and may be intimately linked to epileptogenesis. Impairment of 
astrocytic buffering mechanisms for glutamate and potassium has been identified 
in TSC animal models and human tuber tissue and likely promotes neuronal 
excitability and seizures in TSC. Targeting these defects in astrocytes may 
represent a novel therapeutic strategy for epilepsy in patients with TSC.