Modifications in the Seizures Susceptibility by Excitotoxic Neuronal Damage and Its Possible Relationship with the Pharmacoresistance

The neuronal damage and seizures are two processes closely related not only as cause and effect in reciprocal way but also through the cellular mechanisms and signaling pathways that they share. Therefore, increments in extracellular levels of the glutamate excitatory neurotransmitter, the over-activation of its receptors and the excessive neuronal excitation, have been described as events associated to both processes. In general, if neurons are not able to recover from its excessive excitation, then they die by excitotoxicity. Our group has showed that the excitotoxicity induced by monosodium glutamate in early developmental stages is able to produce significant modifications in glutamatergic and GABAergic neurotransmission systems. Moreover, preliminary results indicate that those modifications are able to increase the seizure susceptibility in the adulthood, particularly when the convulsive drug 4-aminopyridine and the GABA antagonists are employed to induce the seizures, but not when NMDA agonists are used. Through this chapter the topics mentioned above and the hypothesis about the excitotoxic neonatal damage is able to induce a kind of pharmacoresistance to NMDA analogs will be discussed with in detail.