[Effects of thyrotropin-releasing hormone (TRH) on status epilepticus in rats].
Recent studies have demonstrated that intramuscular administration of thyrotropin-releasing hormone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against status epilepticus. However, it is also true that intravenous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats. Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 micrograms of dibutyryl-cAMP (db-cAMP) and 67.2ng of ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water) was administered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Although 3 mg/kg of TRH (n = 9), when injected i.v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n = 5) and 50 mg/kg (n = 5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and lasting for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 micrograms of i.c.v. TRH (n = 5), like higher doses of i.v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immediately after the injection and lasting for about 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Osonoe
K
K
Department of Neuropsychiatry, Fukushima Medical College, Japan.
Mori
N
N
Ohno
E
E
Kumashiro
H
H
D000818:Animals; D004492:Edetic Acid; D004569:Electroencephalography; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000627:therapeutic use*
D013973:Thyrotropin-Releasing Hormone; D004492:Edetic Acid