Abstracts

Mesial temporal lobe epilepsy (mTLE) is one of the most frequent intractable human epilepsies. The lithium-pilocarpine (Li-pilo) model of epilepsy reproduces the main clinical, neuropathological and developmental features of human mTLE. The consequences of Li-pilo-induced status epilepticus (SE) are age-dependent and immature rats do not develop lesions or epilepsy. Metabolic levels and substrate supply to the brain differ largely between adult and immature rats and could be partly responsible for these age-related differences. It is well known that the brain undergoes large metabolic increases during seizure activity. Therefore, we wanted to explore the age-related differences in the regulation of the supply of metabolic substrates to the brain during seizures. Thus, we studied the consequences of Li-pilo-induced SE on the transporters of substrates to the brain.
This study determined the temporal consequences of Li-pilo-induced SE on mRNA levels of three nutrient transporters in brain: GLUT-1 and GLUT-3 for glucose and MCT-1 for monocarboxylates, by in situ hybridization with ³⁵S-labeled riboprobes. Li-pilo SE was performed in 10 and 21 day-old and adult rats. Changes in transporter mRNAs were studied during the acute, silent and chronic phases of the epilepsy. Levels of mRNAs were quantified from autoradiograms by densitometry in 26 regions. Bilateral analysis of variance followed by Fisher[rsquo]s LSD test was performed to compare statistically significant differences between Li-Pilo and saline-injected age-paired rats.
Gene expressions of transporters of cerebral metabolic substrates were mostly affected during SE. Upregulation of the endothelial and glial glucose transporter, GLUT-1, was widespread and progressively more marked with increasing age, whereas upregulation of the monocarboxylate endothelial and glial transporter, MCT-1 was restricted to the circuit of seizures and specifically intense in adult rats. The expression of the neuronal glucose transporter, GLUT-3, was largely increased in younger animals and only moderately in adult animals. During the silent and chronic phases, in adult and P21 rats, the expression of GLUT-1 and MCT-1 tended to remain upregulated while GLUT-3 was down-regulated in areas with marked damage.
Changes during the acute phase show a clear adaptability of the immature brain to the large metabolic demand during SE. The high MCT-1 together with low neuronal GLUT-3 levels in adult rats during SE could reflect neuronal stress leading to neuronal damage. Conversely, high GLUT-3 in immature rats could protect the immature rat brain against lesions. Late changes in the gene expression of these transporters reflect brain damage in adult and 21 day-old rats.
[Supported by: INSERM U405, FRANCE
Pennsylvania State University College of Medicine, USA]