Adenosine A1 receptors are crucial in keeping an epileptic focus localized

Adenosine is an endogenous neuromodulator with anticonvulsant and neuroprotective properties presumably mediated by activation of adenosine A, receptors (A(1)Rs). To study the involvement of A(1)Rs in neuroprotection during epileptogenesis, we induced status epilepticus by a unilateral intrahippocampal kainic acid (KA) injection (1 nmol) in wild-type C5713L/6 and homozygous adenosine AIR knock out (AIR-KO) mice of the same genetic background. Whereas the KA injection caused non-convulsive status epilepticus in wild-type mice, in AIR-KO mice KA induced status epilepticus with severe convulsions and subsequent death of the animals within 5 days. 24 It after KA injection, brains from wildtype C5713L/6 mice were characterized by slight neuronal cell loss confined to the immediate location of the KA injection. In contrast, KA-injected A(1)R-KO mice displayed massive neuronal cell loss in the ipsilateral hippocampus, and, importantly, the contralateral hippocampus was also affected with significant cell loss in the hilus and in the CA1 region of the pyramidal cell layer. We conclude that activation of A, receptors by ambient adenosine is crucial in keeping epileptic foci localized. These results open up a new dimension of the A, receptor's role in controlling excitotoxic cell death and further demonstrate its importance in preventing the progression of status epilepticus to lethal consequences. (c) 2006 Elsevier Inc. All rights reserved.