Pilocarpine model of temporal lobe epilepsy shows enhanced response to general anesthetics.
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 GABAA 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.
Long
Jennifer J A
JJ
Department of Physiology and Pharmacology, Medical Science Bldg, University of Western Ontario, London, Ontario, Canada N6A 5C1.
Shen
Bixia
B
Luo
Tao
T
Stewart
Lee
L
McMurran
Thomas J A
TJ
Leung
L Stan
LS
D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003244:Consciousness Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D003292:Convulsants; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology*; D018755:GABA Agonists / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010424:Pentobarbital / Q000494:pharmacology; D010862:Pilocarpine; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology
D018681:Anesthetics, General; D003292:Convulsants; D018755:GABA Agonists; D010862:Pilocarpine; D009118:Muscimol; D010424:Pentobarbital; D006221:Halothane; D015742:Propofol