Adeno associated viral vector-mediated expression of somatostatin in rat hippocampus suppresses seizure development

Somatostatin (SST) has been suggested to play an important role in maintaining hippocampal homeostasis by modulating excitatory neurotransmission. The putative anticonvulsant role for SST was tested in an electrical amygdala kindling model. SST was cloned into serotype 5 of the adeno-associated viral (AAV) vector and delivered bilaterally into the hippocampus of adult male Sprague Dawley rats that were subsequently electrically kindled. Behavioral severity and duration of kindled seizures was compared to uninjected and GFP-injected control rats. Results demonstrated that 70% of SST treated animals did not experience class IV or V seizures without affecting the threshold for individual stimulation-evoked seizures. This result was significantly different from control groups where 100% of animals reached class V seizures. No difference in the number of stimulations required to reach the first class I-III seizures was observed in the experimental cohort relative to age-matched controls. These preclinical results suggest a putative role for SST as an anticonvulsant therapeutic modality for epilepsy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.