Siddiqui Adnan H, Joseph Shirley A
Department of Neurosurgery, Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Brain Res. 2005 Dec 20;1066(1-2):129-46. doi: 10.1016/j.brainres.2005.10.066.
Latency between an early neurological insult and development of spontaneous recurrent seizures suggests aberrant chronological reorganization in patients with mesial temporal sclerosis associated epilepsy. Kainate-induced status similarly results in delayed development of spontaneous recurrent seizures. Mossy fiber sprouting by the dentate granule cells is a well-characterized manifestation of such temporal structural reorganization in both patients and animal models. However, alterations in other components of hippocampal circuitry have not been evaluated. We present results from studies using precise anterograde and retrograde tract tracing methodologies to evaluate the reorganization of outflow of the CA3 pyramidal cells. Although septotemporal relationships of the normal CA3 outflow tract through the Schaffer collaterals are well known, their aberrant reorganization following kainate-induced spontaneous recurrent seizures is not known. We provide the first definitive evidence of widespread CA3 structural reorganization in the form of sprouting of CA3 axons to widespread areas throughout the hippocampus and entorhinal cortex. This includes an apparent increase in the density of projection to areas that normally receive CA3 outflow such as CA1 and subiculum as well as novel projections beyond the confines of the hippocampus to the pre and parasubiculum and medial and lateral entorhinal cortex. We provide the first evidence of novel CA3 Schaffer collateral projection to the entorhinal cortex. The sprouting of CA3 outflow to widespread regions of the hippocampus and the entorhinal cortex may provide insight into how the injured hippocampus propagates unconventional impulse excitation to cortical fields which have a critical role in providing excitatory inputs into the hippocampus possibly setting up reverberating excitatory circuits as well as widespread connections throughout the cortical mantle. Sprouting-related mechanisms may also explain the latency associated with development of spontaneous recurrent seizures, the hallmark of temporal lobe epilepsy.
早期神经损伤与自发性反复癫痫发作之间的潜伏期表明，内侧颞叶硬化相关癫痫患者存在异常的时间顺序重组。海藻酸盐诱导的癫痫持续状态同样会导致自发性反复癫痫发作的延迟出现。齿状颗粒细胞的苔藓纤维出芽是患者和动物模型中这种时间结构重组的一个特征明显的表现。然而，海马回路其他成分的改变尚未得到评估。我们展示了使用精确的顺行和逆行束路追踪方法进行研究的结果，以评估CA3锥体细胞传出纤维的重组情况。虽然正常情况下通过海马联合纤维的CA3传出纤维束的颞叶前后关系是众所周知的，但在海藻酸盐诱导的自发性反复癫痫发作后其异常重组情况尚不清楚。我们首次提供了确凿证据，证明CA3存在广泛的结构重组，表现为CA3轴突向海马和内嗅皮质的广泛区域出芽。这包括向正常接收CA3传出纤维的区域（如CA1和海马下脚）的投射密度明显增加，以及超出海马范围向海马旁前区和旁区以及内侧和外侧内嗅皮质的新投射。我们首次证明了CA3海马联合纤维向内嗅皮质的新投射。CA3传出纤维向海马和内嗅皮质广泛区域的出芽可能有助于深入了解受损海马如何将非常规的冲动兴奋传递到皮质区域，这些皮质区域在向海马提供兴奋性输入方面起着关键作用，可能会建立起回荡性兴奋回路以及贯穿整个皮质层的广泛连接。与出芽相关的机制也可能解释与自发性反复癫痫发作（颞叶癫痫的标志）发展相关的潜伏期。
