A means to avoid the pharmacokinetic problems affecting the anti-epileptic drugs may be their direct intracerebroventricular (ICV) or intracerebral delivery. This approach may achieve a greater drug concentration at the epileptogenic area while minimizing it in other brain or systemic areas, and thus it could be an interesting therapeutic alternative in drug-resistant epilepsies. The objective of this article is to review a series of experiments, ranging from actute ICV injection to continuous intracerebral infusion of anti-epileptic drugs or grafting of neurotransmitter producing cells, in experimental models, especially in the kindling model of epilepsy in the rat.Acute ICV injection of phenytoin, phenobarbital or carbamacepine is able to diminish the intensity of kindling seizures, but it is also associated with a high neurologic toxicity, especially phenobarbital. Continuous ICV infusion of anti-epileptic drugs can effectively control seizures, but neurologic toxicity is not improved compared with systemic delivery. However, systemic toxicity may be improved, as in the case of valproic acid, whose continuous ICV infusion results in very low plasmatic or hepatic drug concentrations. Continuous intracerebral infusion at the epileptogenic area was studied as an alternative to minimize neurologic toxicity. Thus, intra-amygdalar infusion of gamma-aminobutyric acid (GABA) controls seizures with minimal neurotoxicity in amygdala-kindled rats. Similarly, continuous infusion of GABA into the dorsomedian nucleus of the thalamus improves seizure spread, while not affecting the local epileptogenic activity at the amygdala. Grafting of GABA releasing cells may reduce kindling parameter severity without behavioral side effects.We may conclude that ICV or intracerebral delivery of anti-epileptic drugs or neurotransmitters may be a useful technique to modulate epilepsy.

中文翻译：

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在点燃模型中进行脑室内和脑内递送抗癫痫药物。


避免影响抗癫痫药物的药代动力学问题的一种方法可能是直接脑室内（ICV）或脑内给药。这种方法可以在致癫痫区域实现更高的药物浓度，同时最大限度地减少其他大脑或全身区域的药物浓度，因此它可能是耐药性癫痫的一种有趣的治疗替代方案。本文的目的是回顾一系列实验，从急性ICV注射到持续脑内输注抗癫痫药物或移植神经递质产生细胞，在实验模型中，特别是在大鼠癫痫的点燃模型中。 ICV 注射苯妥英、苯巴比妥或卡马西平能够降低引发癫痫发作的强度，但也与高神经毒性有关，尤其是苯巴比妥。持续ICV输注抗癫痫药物可以有效控制癫痫发作，但与全身给药相比，神经毒性并未得到改善。然而，全身毒性可能会得到改善，例如丙戊酸，其连续ICV输注会导致血浆或肝脏药物浓度非常低。研究了在致癫痫区域进行连续脑内输注作为尽量减少神经毒性的替代方案。因此，杏仁核内输注γ-氨基丁酸（GABA）可以控制杏仁核点燃大鼠的癫痫发作，同时神经毒性最小。同样，将 GABA 持续注入丘脑背核可改善癫痫发作扩散，同时不影响杏仁核的局部致癫痫活动。移植 GABA 释放细胞可以降低点燃参数的严重程度，而不会产生行为副作用。我们可以得出结论，ICV 或脑内递送抗癫痫药物或神经递质可能是调节癫痫的有用技术。