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内侧神经节隆起前体细胞移植对匹罗卡品癫痫模型皮质-海马振荡的修饰作用。

Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

机构信息

Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP/SP), São Paulo, Brazil.

Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Graduate Program in Neuroscience, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

出版信息

Epilepsy Behav. 2024 Oct;159:110027. doi: 10.1016/j.yebeh.2024.110027. Epub 2024 Aug 31.

Abstract

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

摘要

使用内侧神经节隆起(MGE)衍生的 GABA 能前体细胞的细胞替代疗法通过在癫痫动物模型中恢复抑制作用来减少癫痫发作。然而,MGE 衍生细胞如何影响异常神经元网络,从而减少癫痫发作的发生,仍在研究中。我们对在匹罗卡品癫痫大鼠模型中体内记录的皮质和海马 CA1 区的癫痫发作前局部场电位(LFP)进行了定量分析,分别有无海马内 MGE 前体细胞移植(PILO 和 PILO+MGE 组)。PILO+MGE 动物的癫痫发作次数明显减少。癫痫发作前 LFP 的定量分析显示,两组皮质和海马的δ、θ和β振荡的功率从 5 分钟的发作间期基线降低到 20 秒的发作前。然而,与 PILO 组相比,PILO+MGE 动物的皮质和海马中的慢波和快波的功率更高,而慢波和快波的功率更低。此外,与 PILO 动物相比,PILO+MGE 动物在癫痫发作起始时表现出θ和γ振荡的皮质-海马同步性降低,以及慢γ振荡时海马 CA1 区δ和θ之间的同步性降低。这些发现表明,MGE 衍生细胞整合到异常重连的网络中可能有助于控制癫痫发作的发生。

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