Alpha 2-adrenoceptor agonist, dexmedetomidine, protects against kainic acid-induced convulsions and neuronal damage.
Kainic acid (KA)-induced convulsions are accompanied by histopathological changes that are most prominent in the temporal lobe structures. In the present study, we investigated whether a selective alpha2-adrenoceptor agonist, dexmedetomidine could attenuate KA-induced epileptic convulsions and subsequent neuronal damage in the rat hippocampus. Rats were pretreated 30 min before KA injection (9 mg/kg, i.p.) with dexmedetomidine (3 micrograms/kg, s.c.). The behavior of animals was observed for at least 3 h. Dexmedetomidine suppressed the development (p < 0.001), generalization (p < 0.05) and severity (p < 0.01) of convulsions. In addition, histological analysis revealed that dexmedetomidine-treated animals without convulsions or with only partial convulsions had no neuronal damage in the principal cell layers of the hippocampus. A selective alpha2-antagonist, atipamezole (1 mg/kg, s.c.) potentiated KA-induced convulsions and increased the mortality in status epilepticus. In conclusion, the present study demonstrated that dexmedetomidine, in addition to possessing anticonvulsant properties, has a neuroprotective effect in the KA model of status epilepticus.
Halonen
T
T
Department of Neurology, University of Kuopio, Finland.
Kotti
T
T
Tuunanen
J
J
Toppinen
A
A
Miettinen
R
R
Riekkinen
P J
PJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology; D006651:Histocytochemistry; D007093:Imidazoles / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D020926:Medetomidine; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D013226:Status Epilepticus / Q000188:drug therapy; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000927:Anticonvulsants; D007093:Imidazoles; C050701:atipamezole; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D020926:Medetomidine; D007608:Kainic Acid