在海人酸大鼠模型中，早期生活状态癫痫发作后海马下托和CA3区的突触重组。
Synaptic reorganization in subiculum and CA3 after early-life status epilepticus in the kainic acid rat model.
作者信息
Cross Devin J, Cavazos José E
机构信息
Department of Medicine (Neurology), University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
出版信息
Epilepsy Res. 2007 Feb;73(2):156-65. doi: 10.1016/j.eplepsyres.2006.09.004. Epub 2006 Oct 27.
PURPOSE
The immature rat brain is highly susceptible to seizures, but has a resistance to pathological changes induced by seizures as compared to adult rats. However, prolonged seizures during early-life enhance cellular injury and hyperexcitability induced by convulsive insults later in adulthood. The mechanisms underlying these phenomena are not understood. In adult models, the CA1 axons reorganize their projections to subiculum. Seizure induced plasticity in this pathway has not been investigated in immature seizure models, and may contribute to the vulnerability to later seizures.
METHODS
On postnatal day 15, rats experienced convulsive status epilepticus with kainic acid (KA). Seizure induced plasticity was examined with Timm histochemistry and iontophoretic injections of sodium selenite, a retrograde tracer. Cellular injury was evaluated with Fluoro-Jade B histochemistry.
RESULTS
Retrograde tracing experiments determined a 67% larger dorsoventral extent of retrograde labeling in the CA1 pyramidal region after tracer injections in subiculum. The synaptic reorganization of the CA1 projection to subiculum was noted in the absence of overt neuronal injury in subiculum or CA1. In contrast, mossy fiber sprouting was detected into the stratum oriens of CA3 with limited neuronal injury to CA3 pyramidal neurons. No mossy fiber sprouting into the inner molecular layer of the dentate gyrus, or CA1 sprouting into the stratum moleculare of CA1 were noted.
CONCLUSIONS
The results indicate that the developing brain has distinct mechanisms of seizure induced reorganization as compared to the adult brain. Our experiments show that the concept of "resistance of the immature brain to excitotoxicity" is considerably more complicated than generally believed. Morphological plasticity in the immature brain appears more extensive in distal, but not proximal, projections of hippocampal pathways, and across hippocampal lamellae. The abnormal connectivity between hippocampal lamellae might play a role in the increased susceptibility to injury and hyperexcitability associated with later convulsive insults.
目的
幼龄大鼠的大脑对癫痫发作高度敏感，但与成年大鼠相比，对癫痫发作诱导的病理变化具有抵抗力。然而，生命早期的长时间癫痫发作会加重成年后期惊厥性损伤诱导的细胞损伤和兴奋性过高。这些现象背后的机制尚不清楚。在成年模型中，CA1轴突会重新组织其向海马下托的投射。在未成熟癫痫模型中尚未研究该通路中癫痫发作诱导的可塑性，其可能导致对后期癫痫发作的易感性。
方法
出生后第15天，大鼠用红藻氨酸（KA）诱发惊厥性癫痫持续状态。用Timm组织化学法和离子电渗法注射逆行示踪剂亚硒酸钠检测癫痫发作诱导的可塑性。用Fluoro-Jade B组织化学法评估细胞损伤。
结果
逆行追踪实验确定，在海马下托注射示踪剂后，CA1锥体区域逆行标记的背腹范围增大了67%。在海马下托或CA1没有明显神经元损伤的情况下，观察到CA1向海马下托投射的突触重组。相比之下，在CA3锥体神经元神经元损伤有限的情况下，检测到苔藓纤维向CA3的原层发芽。未观察到苔藓纤维向齿状回内分子层发芽，或CA1向CA1分子层发芽。
结论
结果表明，与成年大脑相比，发育中的大脑具有不同的癫痫发作诱导重组机制。我们的实验表明，“未成熟大脑对兴奋性毒性的抵抗力”这一概念比一般认为的要复杂得多。未成熟大脑中的形态可塑性在海马通路的远端而非近端投射以及整个海马板层中似乎更为广泛。海马板层之间的异常连接可能在与后期惊厥性损伤相关的损伤易感性增加和兴奋性过高中起作用。
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