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细胞移植治疗颞叶癫痫的研究进展。

Progress in cell grafting therapy for temporal lobe epilepsy.

机构信息

Institute for Regenerative Medicine, Texas A&M Health Science Center at Scott & White, Department of Molecular and Cellular Medicine, Temple, TX 76502, USA.

出版信息

Neurotherapeutics. 2011 Oct;8(4):721-35. doi: 10.1007/s13311-011-0064-y.

Abstract

Temporal lobe epilepsy (TLE), exemplified by complex partial seizures, is recognized in ~30% of epileptic patients. Seizures in TLE are associated with cognitive dysfunction and are resistant to antiepileptic drug therapy in ~35% of patients. Although surgical resection of the hippocampus bestows improved seizure regulation in most cases of intractable TLE, this choice can cause lasting cognitive deficiency and reliance on antiepileptic drugs. Thus, alternative therapies that are proficient in both containing the spontaneous recurrent seizures and reversing the cognitive dysfunction are needed. The cell transplantation approach is promising in serving as an adept alternate therapy for TLE, because this strategy has shown the capability to curtail epileptogenesis when used soon after an initial precipitating brain injury, and to restrain spontaneous recurrent seizures and improve cognitive function when utilized after the occurrence of TLE. Nonetheless, this treatment needs further advancement and rigorous evaluation in animal prototypes of chronic TLE before the conceivable clinical use. It is especially vital to gauge the efficacy of distinct donor cell types, such as the hippocampal precursor cells, γ-aminobutyric acid-ergic progenitors, and neural stem cells derived from diverse human sources (including the embryonic stem cells and induced pluripotent stem cells) for longstanding seizure suppression using continuous electroencephalographic recordings for prolonged periods. Additionally, the identification of the mechanisms underlying the graft-mediated seizure suppression and improved cognitive function, and the development of apt grafting strategies that enhance the anti-seizure and pro-cognitive effects of grafts will be necessary. The goal of this review is to evaluate the progress made hitherto in this area and to discuss the prospect for cell-based therapy for TLE.

摘要

颞叶癫痫(TLE),以复杂部分性发作为例,在约 30%的癫痫患者中被识别。TLE 发作与认知功能障碍有关,约 35%的患者对抗癫痫药物治疗有抵抗力。尽管海马切除术在大多数难治性 TLE 病例中能更好地控制发作,但这种选择会导致持续的认知缺陷和对抗癫痫药物的依赖。因此,需要寻找既能控制自发性反复发作又能逆转认知功能障碍的替代疗法。细胞移植方法有望成为 TLE 的一种熟练替代疗法,因为这种策略在初次诱发脑损伤后不久使用时显示出抑制癫痫发生的能力,并且在 TLE 发生后使用时可以抑制自发性反复发作并改善认知功能。然而,这种治疗方法需要在慢性 TLE 的动物模型中进一步发展和严格评估,然后才能在临床应用。评估不同供体细胞类型(如海马前体细胞、γ-氨基丁酸能祖细胞和源自不同人类来源的神经干细胞(包括胚胎干细胞和诱导多能干细胞)的疗效尤为重要,这些细胞类型需要通过长时间的连续脑电图记录来评估其对长期发作的抑制作用。此外,需要确定移植物介导的发作抑制和认知功能改善的机制,并开发合适的移植策略,以增强移植物的抗发作和促认知作用。本综述的目的是评估该领域迄今取得的进展,并讨论细胞治疗 TLE 的前景。

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