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成年和未成年遗传癫痫大鼠模型的局部脑葡萄糖利用情况

Local cerebral glucose utilization in adult and immature GAERS.

作者信息

Nehlig A, Vergnes M, Boyet S, Marescaux C

机构信息

INSERM U 398, Université Louis Pasteur, Faculté de Médecine, Strasbourg, France.

出版信息

Epilepsy Res. 1998 Sep;32(1-2):206-12. doi: 10.1016/s0920-1211(98)00052-7.

Abstract

In the present study, we compared the basal local cerebral metabolic rates for glucose (LCMRglcs) both in Wistar rats with genetic absence epilepsy (GAERS: genetic absence epilepsy rats from Strasbourg) and in control non epileptic (NE) rats selected in our breeding colony. LCMRglc was measured both in immature rats at postnatal day 21 (P21) at which age no spontaneous spike-and-wave discharges can be recorded in GAERS and at the adult age (6 months) when GAERS fully express thalamo-cortical spike-and-wave discharges recorded on the EEG. LCMRglcs were measured in 24 structures by the quantitative [14C]2-deoxyglucose autoradiographic technique. In adults GAERS, LCMRglc underwent a widespread increase recorded in all brain structures except in mediodorsal and ventromedian thalamus, and in the nucleus accumbens. These metabolic increases ranged from 17 to 50% over control levels in adult NE rats. In P21 GAERS, LCMRglc was similar to that of P21 NE rats in 16 areas. It increased over control levels of NE rats in two groups of structures. Metabolic increases were recorded in four limbic structures (entorhinal and piriform cortices, hippocampus and basolateral amygdala) where no spike-and-wave discharges were recorded in adult GAERS. Increases in LCMRglcs were also located in the substantia nigra pars reticulata, superior colliculus and globus pallidus which are structures involved in the control of seizure activity. In conclusion, our data suggest that the consequences of the genetic mutation(s) underlying the cellular and molecular events responsible for the expression of spike-and-wave discharges in adult GAERS is (are) able to increase metabolic activity in both limbic structures and the nigral inhibitory system before the occurrence of spike-and-wave discharges.

摘要

在本研究中,我们比较了遗传性失神癫痫的Wistar大鼠(GAERS:来自斯特拉斯堡的遗传性失神癫痫大鼠)和我们繁殖群体中挑选出的对照非癫痫(NE)大鼠的基础局部脑葡萄糖代谢率(LCMRglcs)。在出生后第21天(P21)的未成熟大鼠中测量LCMRglc,在这个年龄GAERS中无法记录到自发的棘波和慢波放电;在成年期(6个月)测量LCMRglc,此时GAERS在脑电图上充分表现出丘脑 - 皮质棘波和慢波放电。通过定量[14C]2 - 脱氧葡萄糖放射自显影技术在24个结构中测量LCMRglcs。在成年GAERS中,除了丘脑背内侧和腹内侧以及伏隔核外,所有脑结构中的LCMRglc都出现了广泛增加。这些代谢增加比成年NE大鼠的对照水平高出17%至50%。在P21的GAERS中,16个区域的LCMRglc与P21的NE大鼠相似。在两组结构中,它超过了NE大鼠的对照水平。在成年GAERS中未记录到棘波和慢波放电的四个边缘结构(内嗅皮质和梨状皮质、海马体和基底外侧杏仁核)中记录到了代谢增加。LCMRglcs的增加也位于黑质网状部、上丘和苍白球,这些都是参与癫痫活动控制的结构。总之,我们的数据表明,在成年GAERS中负责棘波和慢波放电表达的细胞和分子事件背后的基因突变后果能够在棘波和慢波放电出现之前增加边缘结构和黑质抑制系统中的代谢活动。

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