摘要
目的探讨不同发育期大鼠癫发病机制。方法对P10、P20、P603组大鼠,用戊四氮反复点燃5d,设生理盐水对照组;观察各组大鼠行为学改变,海马神经元形态、神经元计数、苔藓纤维发芽、NF-κB表达。结果(1)点燃后P10、P20组惊厥潜伏期、潜伏发作期较P60短,惊厥持续时间较P60长(F=103·28,132·65,P均<0·05);(2)P10、P20实验组海马各区无明显神经元丢失;P10DG区颗粒细胞计数较对照组增多;P60CA1、CA3区神经元较对照组明显减少,DG区无改变;(3)各组海马CA3区均可见苔藓纤维发芽,其中P60组较P10、P20组明显;(4)各实验组NF-κB阳性表达细胞较对照组均增多,且随鼠龄增加NF-κB光密度值逐渐减弱,差异均有统计学意义(P<0·05)。结论(1)不同发育期大鼠惊厥易感性存在差异;(2)发育鼠致后海马神经元损伤、病理性苔藓纤维发芽较轻,可能为对惊厥耐受性较好的病理学证据;(3)NF-κB在惊厥性脑损伤过程中发挥一定生物学效应。
Objective To observe the histopathological changes in rat hippocampus at different maturational stages after repeated kindled seizures, and to explore their underlying epileptogenesis processes. Methods Three groups of Wistar rats (postnatal days: P10, P20, P60) were given pentylenetetrazol (PTZ) intraperitoneal injection for 5 days to induce repeated kindled seizures, and the age-matched rats in control group were injected with normal saline. The behavioral changes, the morphology and the neurons counting in hippocampus, as well as the expression of NF-κB were observed. Results ( 1 ) In the three groups, the latency of seizure and the latency of Ⅳ/Ⅴgrade were significantly lower in the rats of group P10 and P20 [ ( 1.2 ± 0. 6) min and ( 14.4 ± 2. 3 ) min vs. ( 4. 7 ± 1.6 ) min and ( 24. 5 ± 4.5 ) min ] than group P60 [ ( 8.6 ± 2. 0) min and ( 41.9 ± 4. 5 ) min ] , whereas the duration of convulsion in group P10 and P20 [ (46. 2 ± 4. 8 ) min and ( 29. 8 ± 5.9 ) min] was longer than those of group P60 [ ( 17.1 ± 5.0) min ]. ( 2 ) The neuron counting of CA1, CA3 and hilar in the P10 and P20 groups showed no differences as compared to their controls, whereas adult rats (P60) had a significant neuron loss in CA1 and CA3 pyramidal cells, compared with the control group [(6.3 ± 1.5)/250 μm^2,(3.6 ± 1.4)/250 μm^2 vs. (8.2 ± 1.9)/250 μm^2,(5. 6 ± 1.7)/250 μm^2 ]. However, the dentate granule cells in immature rats (P10) with daily seizures had a significant increase as compared with the controls [ (23.3 ± 3. 1 )/250 μm^2 vs. (16. 3 ± 1.6)/250 μm^2 ]. (3) Prominent sprouting was seen in the CA3 stratum pyramidal layer in all experimental rats with 5 daily seizures, regardless of the age. But the degree of sprouting had significant differences among the experimental groups (P 〈 0. 05 ). (4) NF-κB was expressed significantly in CA3, CA1 and dentate granule cells 24 hours after PTZ-kindling when compared with the control groups, with the spectral density decreased with age. Conclusion (1) There were great differences in the vulnerability to the repeated seizure-induced brain damage at different maturational stages in rats. The immature brain appeared to be less vulnerable to the repeated seizures. (2) There was less hippocampus neuron loss and milder mossy fiber sprouting after repeated seizures in the developing rats than mature ones, which may be a pathological evidence underlying the prospect that the immature brain was more resistant to the seizure-induced neuronal injury. (3) The high expression of NF-κB may exert a certain biological effects in the seizure-induced neuronal injury.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2005年第12期930-934,共5页
Chinese Journal of Pediatrics
基金
湖北省自然科学基金资助项目(2004ABA234)