Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy
Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy
复制标题
DOI：
10.1073/pnas.131102898
复制
发表时间：
2001-06-19
影响因子：
11.1
通讯作者：
Boison, D
中科院分区：
文献类型：
--
作者：
Huber, A;Padrun, V;Boison, D
腺苷是大脑中神经元活动的抑制因子。从移植细胞中局部释放腺苷被评估为一种抑制同步放电和癫痫发作的体外基因治疗方法。成纤维细胞被改造成通过灭活腺苷代谢酶腺苷激酶和腺苷脱氨酶来释放腺苷。在被包裹成半透性聚合物后，这些细胞被移植到电点燃的大鼠的脑室，这是一种部分癫痫的模型。精心制作的大鼠提供了对行为癫痫的几乎完全保护，并几乎完全抑制了脑电记录中的后放电，而对照组大鼠的完全强直-阵挛惊厥保持不变。因此，腺苷的局部释放导致作用部位的腺苷浓度达到25 nM，足以抑制癫痫发作活动，因此，为治疗耐药部分性癫痫提供了一种潜在的治疗原则。
Adenosine is an inhibitor of neuronal activity in the brain. The local release of adenosine from grafted cells was evaluated as an ex vivo gene therapy approach to suppress synchronous discharges and epileptic seizures. Fibroblasts were engineered to release adenosine by inactivating the adenosine-metabolizing enzymes adenosine kinase and adenosine deaminase. After encapsulation into semipermeable polymers, the cells were grafted into the brain ventricles of electrically kindled rats, a model of partial epilepsy. Crafted rats provided a nearly complete protection from behavioral seizures and a near-complete suppression of afterdischarges in electroencephalogram recordings, whereas the full tonic-clonic convulsions in control rats remained unaltered. Thus, the local release of adenosine resulting in adenosine concentrations < 25 nM at the site of action is sufficient to suppress seizure activity and, therefore, provides a potential therapeutic principle for the treatment of drug-resistant partial epilepsies.