Adenosine, astrogliosis and seizures: a new perspective of epileptogenesis

Epileptogenesis involves a sequence of events leading from acute brain injury (e.g. status epilepticus, SE), to structural remodeling of affected brain areas including astrogliosis, and finally to recurrent and frequently pharmacoresistant seizures. Animal models of epileptogenesis have shown that the endogenous antiepileptic adenosine-based control system undergoes major changes promoting further seizures. In particular, the astrocytic enzyme adenosine kinase (ADK) is upregulated during epilepsy-associated astrogliosis, thus leading to a reduction of protective adenosine. Likewise transgenic overexpression of ADK leads to spontaneous seizures. Conversely, pharmacological inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. Thus, ADK emerges as a target to predict and to prevent epileptogenesis.