Pilocarpine model of temporal lobe epilepsy shows enhanced response to general anesthetics

Abstract

Complex partial seizures, commonly arising from temporal lobe epilepsy (TLE), are associated with neuronal loss and post-seizure impairment of consciousness. We tested the hypothesis that TLE subjects, in between seizures, are associated with a decreased level of consciousness that is manifested by an enhanced response to a general anesthetic. Two animal models of TLE – amygdala kindling and pilocarpine-induced status epilepticus (Pilo-SE) – were tested. Pilo-SE rats, but not amygdala-kindled rats, showed a prolonged loss of pain and righting responses after 20 and 40 mg/kg i.p. pentobarbital, 2% halothane, and 5 and 10 mg/kg i.v. propofol as compared to control saline-treated rats. Since the major pathology of Pilo-SE rats was cell loss in the piriform cortex (PC) and the entorhinal cortex (EC), we studied the anesthetic response after inactivation of the EC or PC by locally infusing GABA A receptor agonist muscimol. Muscimol inactivation of the PC or EC, as compared to saline infusion in the same rats, prolonged the duration of loss of righting reflex, typically without changing the duration of loss of tail-pinch response, after 20 mg/kg i.p. pentobarbital, 2% halothane and 5 mg/kg i.v. propofol. Muscimol infusion, as compared to saline infusion, in the PC or EC also tended to decrease 30–100 Hz gamma EEG in the frontal cortex. In conclusion, a TLE model that resulted in neuronal loss, Pilo-SE, enhanced the response to a general anesthetic that could partly be attributed to a loss of neurons in the EC and PC.