Department of Pediatrics, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
Seizure. 2011 Mar;20(2):156-9. doi: 10.1016/j.seizure.2010.11.012. Epub 2010 Dec 8.
Adenosine is a potent neuromodulator in the central nervous system (CNS). The functional deterioration of adenosine A(1) receptors in the CNS was reported to cause a failure of termination of seizures and to a lower seizure threshold of hyperthermia-induced seizures (HS) in childhood rats, which may contribute to adenosine-related convulsive disorders such as theophylline-associated seizures in childhood patients. In contrast to the inhibitory effect of adenosine A(1) receptors, the function of adenosine A(2A) receptors remains controversial. To clarify the function of adenosine A(2A) receptors in childhood convulsive disorders associated to hyperthermia, we investigated the in vivo interaction between adenosine A(2A) receptors and their ligands in HS in childhood rats. Adenosine selective A(2A) receptor ligands were injected intraperitoneally before HS. We measured brain temperature at the onset of seizures and the mortality rate after HS. We found that brain temperature at seizure onset was significantly higher in the A(2A) receptor antagonist group compared with that in the control group (p<0.05), and there was no significant difference in mortality among the groups. In contrast, brain temperature at seizure onset was significantly lower in the A(2A) receptor agonist group compared with that in the control group (p<0.05), and mortality was significantly higher in the A(2A) agonist group compared with that in the control group (p<0.001). The activation of the adenosine A(2A) receptor might enhance seizures associated to hyperthermia in the childhood human brain, and be involved in the pathogenesis of sudden unexpected death in epilepsy (SUDEP) in childhood patients with convulsive disorders.
腺苷是中枢神经系统（CNS）中的一种强效神经调质。据报道，CNS 中的腺苷 A(1)受体功能恶化会导致癫痫发作无法终止，并导致儿童高热诱导性癫痫发作（HS）的癫痫发作阈值降低，这可能导致与腺苷相关的癫痫发作障碍，如儿童患者茶碱相关性癫痫发作。与腺苷 A(1)受体的抑制作用相反，腺苷 A(2A)受体的功能仍存在争议。为了阐明与高热相关的儿童癫痫发作中腺苷 A(2A)受体的功能，我们研究了儿童 HS 中腺苷 A(2A)受体及其配体在体内的相互作用。HS 前，通过腹腔内注射选择性腺苷 A(2A)受体配体。我们测量了癫痫发作时的大脑温度和 HS 后的死亡率。我们发现，与对照组相比，A(2A)受体拮抗剂组的癫痫发作起始时大脑温度显著升高（p<0.05），且各组死亡率无显著差异。相比之下，与对照组相比，A(2A)受体激动剂组的癫痫发作起始时大脑温度显著降低（p<0.05），且 A(2A)激动剂组的死亡率显著高于对照组（p<0.001）。A(2A)受体的激活可能会增强儿童大脑中与高热相关的癫痫发作，并参与儿童伴有癫痫发作的突发性意外死亡（SUDEP）的发病机制。
