Laboratoire de Neurophysiologie et Biologie des Comportements Centre de Neurochimie du CNRS 12, Strasbourg (France).
Restor Neurol Neurosci. 1991 Jan 1;3(2):55-64. doi: 10.3233/RNN-1991-3202.
Long-Evans female rats sustained aspirative lesions of the fimbria-fornix pathways and part of the overlying structures (Lesion). Eight or 9 days later, one third of these lesioned rats received intrahippocampal septal cell suspension grafts (Sept-G) and another third received grafts of hippocampal origin (Hipp-G). Sham-operated rats (Sham) served as controls. For each surgical treatment, 3 subgroups were assigned to one of 3 experiments which differed by the delay separating grafting from testing. Three months (EXP1), seven months (EXP2) and twelve months (EXP3) after grafting, rats were tested for reactivity to pentylenetetrazol (PTZ, 30 mg/kg, i.p.) and to sound (10-20 kHz peaks, 120 dB, 90 s), two models of generalized convulsive seizures. Three months after grafting, lesion-only rats showed increased reactivity to PTZ as compared to Sham rats; both types of grafts (Sept-G, Hipp-G) attenuated this lesion-induced effect. Whether 7 or 12 months after grafting, no significant between-group differences were observed anymore. Three months after grafting, reactivity to sound tended to increase in lesion-only rats and was significantly increased in both groups with grafts (Sept-G, Hipp-G) as compared to the Sham group. Seven months after grafting, only Hipp-G rats showed increased reactivity to sound compared to Sham or lesion-only rats. No significant between-group difference was observed at 12 months post-grafting. At all 3 delays, histological analyses revealed well integrated grafts, but only septal grafts provided the denervated hippocampus with an AChE-positive fiber ingrowth. Reactivity to PTZ or to sound was correlated neither with the size of the graft, nor with the acetylcholinesterase (AChE)-positive graft-derived reinnervation of the dorsal hippocampus. The present results suggest that hippocampal denervation may result in a temporary increase in reactivity to PTZ and susceptibility to sound, the former being transitorily attenuated and the latter being transitorily increased by both kinds of grafts. Our data confirm earlier reports showing that grafts may influence sensitivity to convulsive seizure-inducing treatments. In addition, these data indicate that this influence is not necessarily lasting and that the kind and duration of this influence is dependent upon the model of convulsive seizures used.
长爪雌性大鼠接受了穹窿伞纤维束和部分覆盖结构的吸入性损伤(损伤)。 8 或 9 天后,这些损伤大鼠中的三分之一接受了海马隔细胞悬液移植物(Sept-G),另外三分之一接受了海马起源的移植物(Hipp-G)。假手术大鼠(Sham)作为对照。对于每种手术治疗,将 3 个亚组分配到 3 个实验中的 1 个,这 3 个实验的区别在于移植物和测试之间的延迟时间不同。移植物后 3 个月(EXP1)、7 个月(EXP2)和 12 个月(EXP3),大鼠接受戊四氮(PTZ,30mg/kg,ip)和声音(10-20kHz 峰值,120dB,90s)的反应性测试,这是两种全身性惊厥性癫痫发作模型。移植物后 3 个月,仅损伤大鼠对 PTZ 的反应性增加,与 Sham 大鼠相比;两种类型的移植物(Sept-G,Hipp-G)均减弱了这种损伤诱导的作用。无论在移植物后 7 或 12 个月,都不再观察到组间的显著差异。移植物后 3 个月,仅损伤大鼠对声音的反应性倾向于增加,并且与 Sham 组相比,两组移植物(Sept-G,Hipp-G)的反应性均显著增加。移植物后 7 个月,只有 Hipp-G 大鼠对声音的反应性与 Sham 或损伤大鼠相比增加。在移植物后 12 个月时,未观察到组间的显著差异。在所有 3 个延迟时间点,组织学分析显示移植物整合良好,但只有隔神经移植物为去神经的海马提供了乙酰胆碱酯酶阳性纤维的长入。对 PTZ 或声音的反应性既与移植物的大小无关,也与背侧海马的乙酰胆碱酯酶阳性移植物源性再支配无关。本研究结果表明,海马去神经可能导致对 PTZ 的反应性和对声音的敏感性暂时增加,前者暂时减弱,而后者则暂时增加。这两种移植物均可。我们的数据证实了早期的报告,表明移植物可能影响对惊厥性癫痫诱导治疗的敏感性。此外,这些数据表明,这种影响不一定是持久的,并且这种影响的类型和持续时间取决于所使用的惊厥性癫痫发作模型。