不同成熟期大鼠对戊四氮反复致性损伤的耐受性研究

Study on Resistance of Brains at Different Developmental Stages Following Penty lenetetrazol-Induced Recurrent Seizures in Rats

目的 观察不同成熟期大鼠反复惊厥后海马结构的变化 ,并研究发育鼠对惊厥性损伤的耐受性。方法 对生后 10、60d(P10、P60 )实验组大鼠用戊四氮反复点燃 5d ,设P10、P60生理盐水对照组 ;观察两实验组惊厥潜伏期、潜伏发作期、惊厥持续时间 ;海马神经元形态学改变 :海马CA1 、CA3、DG及门区进行细胞计数 ;组织化学染色观察苔藓纤维发芽 ,分别进行实验组间、实验组与对应对照组间比较。结果 1.P10惊厥发作潜伏期 (1.0 7± 0 .5 5 )min、潜伏发作期 (14 .0 0± 2 .70 )min较P60 [(8.2 7± 1.48)、(4 .16± 5 .2 2 )min]短 ,惊厥持续时间 (4 6.3 3± 7.65 )min较成年鼠 (17.0 7± 5 .66)min明显延长 ;2 .P10实验组与对照组比较海马齿状回CA1 、CA3区无明显神经元丢失 ,齿状回DG区颗粒细胞数实验组 (2 3 .2 5± 3 .0 6)较对照组 (16.2 5± 1.5 8)增多。而P60实验组CA1 、CA3区神经元计数 (8.2 2± 1.88、5 .62±l.68)较对照组 (6.3 1± 1.5 0、3 .62± 1.40 )明显减少 ,DG区无明显改变 :3 .Timm染色CA3区锥体层苔藓纤维发芽两实验组均有增加 ,但P60 (3 .2 5±l.0 3 )较P10 (l.5± 0 .92 )更明显 ;以上指标经比较均有显著差异(P均 <0 .0 5 )。结论 1.虽幼鼠较易发生惊厥 ,但致后海马神经元损伤。

Objective To determine if there is an early developmental resistance to seizure-induced hi ppocampal damage. Methods Five daily pentylenetetrazol-indu ced convulsions in immature rats beginning at postnatal day P10,P60 groups.In b oth groups, the latency of seizure, the latency of Ⅳ/Ⅴ grade, the lasting time of seizure and mortality of rats after seizure were used to measure sensitivity of seizure or the resistance to brain damage. Conventional histopathological me thod was utilized to observe morpbological changes and cell counting of dentate granule cells, CA 3,CA 1 and hilar neurnns. Timm histochemical technique was a dopted to study mossy fiber sprou- ting.Results 1.In the both groups(P10,P60),there were significant differences in the latency of seizure (1.07±0.55 vs 8.27±1.48 P<0.05 ),the latency of Ⅳ/Ⅴ grad e (14±2.70 vs 41.6±5.22 P<0.05),the lasting time of seizure(46.33±7. 65 vs 17.07±5.66 P<0.05).2.In immature rats(10 days old),cell counting of CA 1, CA 3 and hilar neurons demonstrated no differences from controIs in rats,whereas adult rats with daily seizures had a significant decrease in CA 1, CA 3 neurons (8.22±l.88、5.62±1.68 vs 6.31± 1.50、3.62±1.40).In adul t rats,cell counting of dentate gradule cells demonstrated no differences from c ontrols in ratas, whereas immiture rats with daily seizures had a significant in crease(23.25±3.058 vs 16.25±1.58).3.Based on Timm staining,prominent sprou ting was seen in the CA 3 stratum pyramidal layer in all experimental rats havi ng 5 daily seizures, regardless of the age. But the degree of sprouting had sign ificant differences between the experimental groups (3.25±1.03 vs 1.5±0.92 P<0.05).Conclusions 1.Though immature rats have prolonged seizures and increased susceptibility th an adult rats, resistance of hippocanipus neuron loss and mossy fiber sprouting aiterations inimmature rats is higher than adult rats. The higher resistance is based on hippocanipus morphologic alterations of immature rats followting rec urrent seizures.2.In the immature rats,recurrent seizures can also result in de ntate granule cell neurogenesis without loss of neurons,which can play an effect on mechanism of mossy fiber sprouting in immature rats. J Appl Clin Pediatr,2005,20(2):160-162