Focal epileptogenesis in a rat model of polymicrogyria
Focal epileptogenesis in a rat model of polymicrogyria
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DOI：
10.1152/jn.1999.81.1.159
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发表时间：
1999-01-01
影响因子：
2.5
通讯作者：
Prince, DA
中科院分区：
文献类型：
--
作者：
Jacobs, KM;Hwang, BJ;Prince, DA
多小脑回是一种与癫痫相关的发育性皮质畸形，可以在出生当天 (P0) 或 P1 具有经皮层冷冻损伤的大鼠中进行建模。我们使用场电位记录来表征实验性小脑回大鼠切片中癫痫样活动的发生率、传播模式和分布。 85% 的 P12-P118 冷冻损伤大鼠切片中诱发了类似发作间期的癫痫样活动。这些数据显示了癫痫发生的年龄特异性，包括：发作延迟、>P40 大鼠中癫痫样活动发生率降低（这是针对 P0 而非 P1 病变的大鼠），以及成熟动物中可能的起始部位转移到远离小脑回的区域。一些观察结果表明，在尼氏染色中组织学上显示正常的小回附近区域包含必要的致癫痫神经元回路：1）在 78% 的切片中，癫痫样活动只能从与小回相邻的局灶区（副小回区）引起，而不是在小回本身内； 2) 癫痫样活动始终源自该副小回区内的特定部位，与刺激电极的位置无关，表明发生器位于小回之外； 3）通过经皮层切割将该区域与小回分离后，副小回皮质中诱发的癫痫样活动没有改变； 4）在副小回带中引起的短潜伏期分级场电位包含在对照切片中未见的额外负性。在成熟和未成熟冷冻损伤大鼠的切片中，N-甲基-D-天冬氨酸受体拮抗剂可逆地阻断癫痫样活动。这些结果表明，异常的突触连接在小脑回周围的大鼠皮层中发育，并产生局灶性致痫区，其产生癫痫样活动的能力并不依赖于与畸形本身的连接。我们假设，源自皮质和皮质外部位的传入神经在畸形区域失去其目标，并在畸形附近的皮层中进行适当的层状接触，从而对该皮层区域产生过多的兴奋性输入。在这种皮质畸形模型中，对特定皮质元件的兴奋性反馈增加可能是参与癫痫发生的因素之一。
Polymicrogyria, a developmental cortical malformation associated with epilepsy, can be modeled in rats with a transcortical freeze lesion on the day of birth (P0) or P1. We have used field potential recordings to characterize the incidence, propagation patterns, and distribution of epileptiform activity in slices from rats with experimental microgyri. Interictal-like epileptiform activity was evoked in slices from 85% of freeze-lesioned rats aged P12-P118. These data show age-specific properties of epileptogenesis, including: a delay in onset, a decrease in the incidence of epileptiform activity in rats >P40 that was specific to those lesioned on P0 as opposed to P1, and a shift in the likely site of initiation to areas further from the microgyrus in mature animals. Several observations suggest that the area adjacent to the microgyrus, which appears histologically normal in Nissl stains, contains the necessary epileptogenic neuronal circuits: 1) in 78% of slices, epileptiform activity could be evoked only from a focal zone adjacent to the microgyrus (paramicrogyral zone) and not within the microgyrus proper; 2) epileptiform activity consistently originated from a particular site within this paramicrogyral zone, independent of the location of the stimulating electrode, suggesting that the generator is outside of the microgyrus; 3) evoked epileptiform activities in the paramicrogyral cortex were unaltered after separation of this zone from the microgyrus with a transcortical cut; and 4) the short-latency graded field potential evoked in the paramicrogyral zone contained an additional negativity not seen in control slices. The epileptiform activity was blocked reversibly by N-methyl-D-aspartate receptor antagonists in slices from mature as well as immature freeze-lesioned rats. These results suggest that aberrant synaptic connectivity develops in rat cortex surrounding the microgyrus and produces a focal epileptogenic zone whose capacity to generate epileptiform activities does not depend on connections with the malformation itself. We hypothesize that afferents, originating from cortical and extracortical sites, lose their targets in the region of the malformation and make appropriate laminar contacts in the cortex adjacent to the malformation, creating an overabundance of excitatory input to this cortical zone. increased excitatory feedback onto specific cortical elements may be one factor involved in epileptogenesis in this model of a cortical malformation.