A prolonged experimental febrile seizure results in motor map reorganization in adulthood

作者：Reid Aylin Y^*; Pittman Quentin J; Teskey G Campbell

来源：Neurobiology of Disease, 2012, 45(2): 692-700.

DOI：10.1016/j.nbd.2011.10.013

• Intracortical microstimulation
• FAST rat
• GABA
• Glutamate
• NKCC1
• KCC2
• Cation-chloride co-transporter
• Lipopolysaccharide
• Kainic acid

Introduction: Clinical studies have suggested that children experiencing a febrile seizure (FS) before the age of 1 year have persistent deficits, but it is unknown whether these seizures lead to permanent cortical reorganization and alterations in function. A FS on the background of increased genetic seizure susceptibility may also lead to negative long-term consequences. Alterations in neocortical motor map expression provide a measure of neocortical reorganization and have been reported in both adults with frontal lobe epilepsy and following seizure induction in experimental models. The objectives of the present study were to determine whether 1) an infantile FS leads to changes to motor map expression in adulthood; 2) long-term cortical reorganization is a function of the age at FS or genetic seizure susceptibility; and 3) different levels of GABA(A) or glutamate receptor subunits or cation-chloride-co-transporters (CCCs) at the time of FS correlate with alterations to motor map expression. %26lt;br%26gt;Materials and methods: FSs were induced in postnatal day 10 (P10) or P14 Long-Evans (LE) rats or in P14 seizure-prone FAST rats by the administration of the bacterial endotoxin lipopolysaccharide (LPS) and a sub-convulsant dose of kainic acid. Ten weeks later intracortical microstimulation was performed to generate motor maps of forelimb movement representations. Sensorimotor neocortex samples were also dissected from naive P10 FAST and P10 and P14 LE pups for western blotting with antibodies against various GABA(A), NMDA, and AMPA receptor subunits and for CCCs. %26lt;br%26gt;Results: Adult FAST rats had larger motor maps with lower stimulation thresholds after a FS at P14, while adult LE rats had significantly lower map stimulation thresholds but similar sized maps after a FS at P10 compared to controls. There were no differences in neocortical motor map size or stimulation thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had significantly lower levels of the GABA(A) receptor alpha 1 subunit, higher levels of the alpha 2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the P14 LE rats. %26lt;br%26gt;Conclusions: A single infantile FS can have long-term effects on neocortical reorganization in younger individuals and those with underlying seizure susceptibility. These changes may be related to an increased level of excitability in the neocortex of younger or genetically seizure-prone rats, as suggested by immaturity of their GABAergic and CCC systems. Given the high incidence of FSs in children, it will be important to gain a better understanding of how age and genetic seizure predisposition may contribute to the long-term sequelae of these events.

• 出版日期2012-2