闭环光解笼锁γ-氨基丁酸抑制局灶性癫痫的试验研究

Epilepsy is a common central nervous system disease that currently has no satisfactory method of treatment. Antiepileptic drug therapy is the preferred treatment, but >30% of patients suffer from a combination of continued seizures and medication toxicity and develop medically intractable epilepsy. While about 5% of intractable epilepsy patients can respond to surgical treatment, there are still about 30% of patients with intractable epilepsy. for which there is currently no effective treatment. Therefore, the development of new therapies to control intractable epilepsy has great significance. This project will expand our previous investigation of the use of light-emitting diodes (LED) for photolysis of caged γ- aminobutyric acid (Caged GABA). We will study the local rapid release of natural inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the seizure onset zone and its effects on the rapid reversal of abnormal neuronal excitability in order to achieve the purpose of suppressing or terminating seizures. We will also improve and utilize our seizure detection system to automatically detect seizures and trigger LED-mediated release of GABA. We will analyze the antiepileptic potential of photolysis of caged γ-GABA in both acute and chronic rat seizure models. The ultimate aim of this study is to develop a closed-loop，integrated， implantable device for the nondestructive control of focal seizures arising from the neocortex of epileptic patients.

癫痫作为一种常见的中枢神经系统疾病，目前尚无十分完善的治疗方法。药物治疗虽为首选，但是多于30%的病人药物控制不满意，成为难治性癫痫。约5%的病人可以接受手术治疗，最终仍有约30%的病人无有效的治疗方法。所以开发新型控制难治性癫痫的药物和治疗装置，对于完善癫痫的治疗具有极为重要意义。本项目在前期工作的基础上，利用发光二极管光解笼锁γ-氨基丁酸，局部快速释放抑制性神经递质γ-氨基丁酸, 在致痫区域，快速逆转神经细胞的异常兴奋，以达到抑制或是终止癫痫发作的目的。我们将改良并利用自主开发的癫痫探测系统，自动探测癫痫发作并启动发光二极管装置，形成闭环光学治疗系统。在大鼠急，慢性癫痫模型上测试光解笼锁γ-氨基丁酸抑制局灶性癫痫的潜力。本研究的最终目的是为开发具有自主知识产权，集合癫痫探测系统和光学技术于一体的闭环；可植入的局灶性癫痫治疗装置提供必要的试验数据。

目前，抗癫痫药物仍是癫痫治疗的首选，但仍有大于30%的患者因药物控制不满意而成为难治性癫痫。虽然部分患者可以通过手术控制癫痫发作，但是致痫灶位于功能区的患者则不适合手术，所以开发可以控制皮层难治性癫痫的新型治疗方法，具有极为重要的意义。本项目在前期工作的基础上，利用可植入体内的微细光纤导管将激光导入体内对笼锁γ-氨基丁酸（Caged γ-aminobutyric acid，Caged-GABA）进行光解，在致痫区局部快速释放抑制性神经递质γ-氨基丁酸，抑制神经细胞的异常兴奋，以达到控制癫痫发作的目的。同时我们应用自主研发的的癫痫探测系统，自动自动启动、终止光照装置，形成闭环光学治疗系统。并在在大鼠急、慢性癫痫模型上利用闭环光学治疗系统探索了光解笼锁γ-氨基丁酸控制局灶性癫痫的最佳笼锁γ-氨基丁酸浓度及光照强度。本研究首次提出了可以有效控制癫痫发作的笼锁γ-氨基丁酸最佳浓度及光照强度。为今后该技术的临床转化研究提供了重要的实验参数。