Necrosis of the substantia nigra, pars reticulate, in flurothyl-induced status epilepticus is ameliorated by the spin trap alpha phenyl-N-tert-butyl nitrone.
The objective of the present study was to explore whether a diffusible free radical scavenger can ameliorate the pan-neurotic lesions of the substantia nigra, pars reticulate (SNPR), which are incurred in rats subjected to status epilepticus of more than 30 min duration. Vehicle-injected animals had flurothyl seizures induced for 45 min. The seizures were then terminated and the animals were recovered for 7 d to allow histopathological evaluation of the SNPR lesions. Drug-treated animals, which were otherwise treated identically, were given either 100-800 mg/ kg of dimethylthiourea (DMTU), a diffusible hydroxyl ion scavenger, or the diffusible spin trap alpha-phenyl N-tert-butyl nitrone (PBN) in a dose of 100 mg/kg i.p.. All animals given DMTU died 2 to 8 h after status epilepticus, but PBN was tolerated well by the animals. The amount of flurothyl required to sustain the electrographic seizures was identical in the vehicle- and drug-injected groups, demonstrating that PBN did not suppress seizure activity. Vehicle-injected animals had large bilateral infarcts localized to the SNPR. Of the six animals treated with PBN, one had a small, unilateral lesions, and in all other animals the SNPR had a normal histological appearance. The results strongly suggest that the pan-necrotic lesions of the SNPR incurred during ongoing seizure activity represent a free radical-mediated lesion.
He
Q P
QP
Laboratory for Experimental Brain research, University of Lund, Sweden.
Smith
M L
ML
Li
P A
PA
Siesjö
B K
BK
D000818:Animals; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D009336:Necrosis; D009589:Nitrogen Oxides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012154:Reticular Formation / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013113:Spin Labels; D013226:Status Epilepticus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; C038983:1,3-dimethylthiourea; D013890:Thiourea