Potent inhibitory effects of glial derived neurotrophic factor against kainic acid mediated seizures in the rat.
Recently messenger RNA (mRNA) for glial derived neurotrophic factor (GDNF), a recently discovered member of the TGF-beta superfamily, was shown to increase in the hippocampus after kainic acid-induced seizures. The possibility that exogenous recombinant human (rh) GDNF may have anticonvulsant properties was investigated using a model of temporal lobe epilepsy in the rat. rhGDNF, vehicle or inactive rhGDNF were injected intracerebroventricularly 1 h before peripheral administration of kainic acid. rhGDNF suppressed kainic acid-induced tonic-clonic convulsions when compared to animals treated with vehicle or inactive rhGDNF. The inhibition of kainic acid-induced seizure activity by rhGDNF also prevented the associated neuronal cell loss in hippocampal, thalamic and amygdaloid regions. These results suggest that rhGDNF should be evaluated in other seizure and acute neural disorders that are associated with excitotoxic processes.
Martin
D
D
Department of Pharmacology, Synergen Inc., Boulder, CO 80301, USA.
Miller
G
G
Rosendahl
M
M
Russell
D A
DA
D000320:Adrenergic Fibers / Q000502:physiology; D000679:Amygdala / Q000166:cytology / Q000503:physiopathology; D000818:Animals; D002452:Cell Count; D002642:Chick Embryo; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology; D007276:Injections, Intraventricular; D007608:Kainic Acid; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013788:Thalamus / Q000166:cytology / Q000503:physiopathology
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D007608:Kainic Acid