Seizure suppression in kindled rats by intraventricular grafting of an adenosine releasing synthetic polymer
Seizure suppression in kindled rats by intraventricular grafting of an adenosine releasing synthetic polymer
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DOI：
10.1006/exnr.1999.7209
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发表时间：
1999-11-01
影响因子：
5.3
通讯作者：
Mohler, H
中科院分区：
文献类型：
--
作者：
Boison, D;Scheurer, L;Mohler, H
腺苷是中枢神经系统中的内源性抑制性神经调质，其抗惊厥活性主要基于抑制兴奋性氨基酸的释放。作为一种新的方法来治疗抗药性部分性癫痫，腺苷释放细胞的移植被预见到提供一个局部和持续的腺苷来源，这种基于细胞的治疗的可行性进行了研究，在本研究中，通过脑室内植入的合成聚合物，释放腺苷。心室植入腺苷释放聚合物的点燃大鼠表现出癫痫发作活动的显著减少。这不仅表现为5级癫痫发作减少了75%，而且还表现为脑电图（EEG）记录中后放电的幅度和持续时间减少。点燃对照大鼠植入牛血清白蛋白（BSA）的聚合物或假手术，继续显示其术前癫痫发作模式。当腺苷以每天20-50 ng的量释放时显示抗癫痫活性。这一发现为将来从腺苷释放细胞释放的腺苷量设定了目标，用于抗癫痫治疗。目前的结果清楚地支持了一种新的治疗癫痫的腺苷释放细胞的基础上的可行性。(C)北京：科学出版社.
Adenosine, an endogenous inhibitory neuromodulator in the central nervous system, exerts anticonvulsant activity that is largely based on the inhibition of the release of excitatory amino acids. As a novel approach to treat pharmacoresistant partial epilepsies, the grafting of adenosine-releasing cells is foreseen to provide a local and sustained source of adenosine, The feasibility of this cell-based therapy was investigated in the present study by the intraventricular implantation of synthetic polymers that release adenosine. Kindled rats with a ventricular implant of an adenosine-releasing polymer showed a profound reduction of seizure activity. This was demonstrated not only by a 75% reduction of grade 5 seizures but also by a reduction of the amplitude and duration of afterdischarges in electroencephalographic (EEG) recordings. Kindled control rats that were implanted with bovine serum albumin (BSA)-containing polymers or were sham operated, continued to show their presurgery seizure pattern. Adenosine displayed antiepileptic activity when released in an amount of 20-50 ng per day. This finding sets the target for the required amount of adenosine to be released from future adenosine-releasing cells for antiepileptic therapy. The present results clearly support the feasibility of a novel therapy for epilepsy based on adenosine-releasing cells. (C) 1999 Academic Press.