伽玛刀对红藻氨酸模型大鼠海马形态学及苔藓纤维变化的影响

Effects of gamma knife on morphological changes of hippocampal formation and mossy fiber sprouting in epileptic rats induced by kainic acid

目的通过红藻氨酸（kainic acid,KA）癫痫大鼠模型的伽玛刀（gamma knife,GK）照射,探讨伽玛刀治疗癫痫的机制,以及伽玛刀与海马苔藓纤维发芽（mossy fiber sprouting,MFS）的关系。方法74只Wistar大鼠分为3组：正常对照组（A组）,红藻氨酸致痫模型大鼠组（B组）,40Gy伽玛刀照射红藻氨酸致痫大鼠组（C组）。应用常规病理、电镜观察海马结构形态学改变,Timm’s银染色组织化学方法观察伽玛刀对海马区苔藓纤维发芽的影响。结果B组可见以CA1、CA3区及齿状回内分子层（innermolecular layer,IML）为主的神经元变性、坏死。C组与B组相比,神经元损伤减轻。对Timm’s染色脑片海马CA3区透明层进行测定,B、C组大鼠海马苔藓纤维均出现明显的发芽现象,CA3区异常Timm’s阳性颗粒光密度值显著高于A组（P〈0.01）;C组与B组相比,1-14d苔藓纤维发芽未见明显减少（P〉0.05）,28-42d显著减少（P〈0.05）。结论海马细胞形态的改变——苔藓纤维发芽,可能是KA大鼠癫痫形成的重要机制。40Gy的伽玛刀照射对减轻神经元的损伤有重要作用,抑制苔藓纤维发芽是主要机制之一。

Objective To investigate the relation between the pathogenesis of epilepsy and the mossy fiber sprouting （MFS） by using gamma knife （GK） radiation in rat model. Methods Seventy-four Wistar rats were randomly divided into 3 experimental groups ： control group （ normal rats, group A） ; rats that underwent kainic acidinduction alone （KA rats, group B） ; KA rats treated by 40 Gy gamma knife （ group C）. Conventional histopathological method and electron microscope were used to observe morphological changes in hippocampal formation. In addition, Timm＇ s silver sulfide staining was used to examine the effect of GK on MFS. Results Hippocampal neuronal degeneration and necrosis, especially in CA1 and CA3 and inner molecular layer （IML） of the dentate gyrus were seen in group B. Fewer apoptotic neurons and milder lesions in neurons at the corresponding time point were revealed in group C than group B. Timm＇ s staining showed that multiple aberrant Timm＇ s granules were found in the IML of the dentate gyrus in groups B and C, but not in group A, The transparent layer of CA3 section of the hippocampus was more pronounced in groups B and C than A（P 〈0.001 ）. No significant difference was noted regarding MFS between group B and group C during 1 - 14 days （P 〉 0. 05 ） ; 28 -42 days later, it became significantly different（P 〈 0.05 ）. Conclusion Changes of cell modality- mossy fiber sprouting of hippocampus may play an important role in the pathogenesis of epilepsy. Gamma knife （40 Gy） has definitive effect on inhibiting neuron mechanism to eliminate eoilensv. damage , in which inhibiting MFS in the hippocampus is main mechanism to eliminate epilepsy.