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Convection-enhanced delivery in the treatment of epilepsy.
Neurotherapeutics ( IF 5.7 ) Pub Date : 2009 , DOI: 10.1016/j.nurt.2009.01.017
Michael A Rogawski 1
Affiliation  

Convection-enhanced delivery (CED) is a novel drug-delivery technique that uses positive hydrostatic pressure to deliver a fluid containing a therapeutic substance by bulk flow directly into the interstitial space within a localized region of the brain parenchyma. CED circumvents the blood-brain barrier and provides a wider, more homogenous distribution than bolus deposition (focal injection) or other diffusion-based delivery approaches. A potential use of CED is for the local delivery of antiseizure agents, which would provide an epilepsy treatment approach that avoids the systemic toxicities of orally administered antiepileptic drugs and bystander effects on non-epileptic brain regions. Recent studies have demonstrated that brief CED infusions of nondiffusible peptides that inhibit the release of excitatory neurotransmitters, including ω-conotoxins and botulinum neurotoxins, can produce long-lasting (weeks to months) seizure protection in the rat amygdala-kindling model. Seizure protection is obtainable without detectable neurological or behavioral side effects. Although conventional diffusible antiepileptic drugs do confer seizure protection when administered locally by CED, the effect is transitory. CED is a potential approach for seizure protection that could represent an alternative to resective surgery in the treatment of focal epilepsies that are resistant to orally-administered antiepileptic drugs. The prolonged duration of action of nondiffusible toxins would allow seizure protection to be maintained chronically with infrequent reinfusions.

中文翻译:

对流增强递送治疗癫痫。

对流增强输送 (CED) 是一种新型药物输送技术,它使用正静水压力将含有治疗物质的流体直接输送到脑实质局部区域内的间隙空间中。CED 绕过血脑屏障并提供比团注沉积(局部注射)或其他基于扩散的递送方法更广泛、更均匀的分布。CED 的一个潜在用途是用于局部递送抗癫痫药,这将提供一种癫痫治疗方法,避免口服抗癫痫药物的全身毒性和对非癫痫大脑区域的旁观者影响。最近的研究表明,短暂的 CED 输注非扩散肽可抑制兴奋性神经递质的释放,包括 ω-芋螺毒素和肉毒杆菌神经毒素,可在大鼠杏仁核点燃模型中产生持久(数周至数月)的癫痫发作保护。可以在没有可检测到的神经或行为副作用的情况下获得癫痫保护。尽管当通过 CED 局部给药时,传统的扩散性抗癫痫药物确实可以提供癫痫发作保护,但效果是短暂的。CED 是一种潜在的癫痫保护方法,可以替代切除手术治疗对口服抗癫痫药物有抵抗力的局灶性癫痫。非扩散性毒素的作用时间延长,可以在不频繁回输的情况下长期维持癫痫发作保护。可以在大鼠杏仁核点燃模型中产生持久(数周到数月)的癫痫发作保护。在没有可检测的神经或行为副作用的情况下可以获得癫痫保护。尽管当通过 CED 局部给药时,传统的扩散性抗癫痫药物确实可以提供癫痫发作保护,但效果是短暂的。CED 是一种潜在的癫痫保护方法,可以替代切除手术治疗对口服抗癫痫药物有抵抗力的局灶性癫痫。非扩散性毒素的作用时间延长,可以在不频繁回输的情况下长期维持癫痫发作保护。可以在大鼠杏仁核点燃模型中产生持久(数周到数月)的癫痫发作保护。在没有可检测的神经或行为副作用的情况下可以获得癫痫保护。尽管当通过 CED 局部给药时,传统的扩散性抗癫痫药物确实可以提供癫痫发作保护,但效果是短暂的。CED 是一种潜在的癫痫保护方法,可以替代切除手术治疗对口服抗癫痫药物有抵抗力的局灶性癫痫。非扩散性毒素的作用时间延长,可以在不频繁回输的情况下长期维持癫痫发作保护。尽管当通过 CED 局部给药时,传统的扩散性抗癫痫药物确实可以提供癫痫发作保护,但效果是短暂的。CED 是一种潜在的癫痫保护方法,可以替代切除手术治疗对口服抗癫痫药物有抵抗力的局灶性癫痫。非扩散性毒素的作用时间延长,可以在不频繁回输的情况下长期维持癫痫发作保护。尽管当通过 CED 局部给药时,传统的扩散性抗癫痫药物确实可以提供癫痫发作保护,但效果是短暂的。CED 是一种潜在的癫痫保护方法,可以替代切除手术治疗对口服抗癫痫药物有抵抗力的局灶性癫痫。非扩散性毒素的作用时间延长,可以在不频繁回输的情况下长期维持癫痫发作保护。
更新日期:2020-09-23
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