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 seizur es were then terminated and the animals were recovered for 7 d to allo w histopathological evaluation of the SNPR lesions. Drug-treated anima ls, which were otherwise treated identically, were given either 100-80 0 mg/kg of dimethylthiourea (DMTU), a diffusible hydroxyl ion scavenge r, or the diffusible spin trap alpha-phenyl N-tert-butyl nitrone (PBN) in a dose of 100 mg/kg IP. All animals given DMTU died 2 to 8 h after status epilepticus, but PBN was tolerated well by the animals. The am ount 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 l arge bilateral infarcts localized to the SNPR. Of the six animals trea ted with PBN, one had a small, unilateral lesions, and in all other an imals the SNPR had a normal histological appearance. The results stron gly suggest that the pan-necrotic lesions of the SNPR incurred during ongoing seizure activity represent a free radical-mediated lesion. Cop yright (C) 1997 Elsevier Science Inc.