title: Substantia nigra damage after fluorothyl-induced seizures in rats worsens after post-seizure recovery: no exacerbation with hyperglycaemia.
abstract: The substantia nigra pars reticularis (SNPR) of rats is highly susceptible to both seizure- and ischaemia-mediated damage. Hyperglycaemic exacerbation of brain damage similar to that observed after global brain ischaemia may also occur in rats with status epilepticus. We tested the hypotheses that hyperglycaemia exacerbates seizure-induced SNPR damage in rats and that SNPR lesions develop rapidly post-seizure. Halothane-anaesthetized, paralysed, and mechanically ventilated rats were prepared for haemodynamic and EEG monitoring. Halothane was discontinued, and mechanical ventilation on 30% oxygen/70% nitrous oxide was continued for 1 h. Three treatment groups (20 rats each) were studied: (1) control, lactated Ringer's solution; (2) equiosmolar control, 40% mannitol; and (3) hyperglycaemia, 50% dextrose. Infusions were started 5 min before seizures were induced with flurothyl 3% administered for either 45 (n = 10) or 75 (n = 10) min. Immediately after seizures, half of the animals underwent cerebral perfusion-fixation with formalin and half were allowed to recover for 2 h post-seizure and then perfused. Brain histology was assessed by light microscopy and scored 0-5 (0 = no damage) for the percentage of eosinophilic neurons and vacuolation in the SNPR. Glucose administration decreased the severity of SNPR damage in rats subjected to 75 min of seizures and 2 h recovery (pathology scores: control, eosinophilic neurons = 3.6, vacuolation = 4.0; hyperglycaemia, eosinophilic neurons = 3.0, vacuolation = 2.75; p < 0.05). SNPR damage was worse after 2 h of recovery (pathology scores: 0 h recovery, eosinophilic neurons = 0.9, vacuolation = 0.1; 2 h recovery, eosinophilic neurons = 3.9, vacuolation = 3.8; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology/CCM, School of Public Health, School of Medicine, University of Pittsburgh, PA 15261.
authors.forename: W A
authors.initials: WA
authors.lastname: Kofke
authors.forename: M
authors.initials: M
authors.lastname: Ahdab-Barmada
authors.forename: M
authors.initials: M
authors.lastname: Rose
authors.forename: C
authors.initials: C
authors.lastname: Clyde
authors.forename: E
authors.initials: E
authors.lastname: Nemoto
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications / Q000473:pathology; D000818:Animals; D004569:Electroencephalography; D005481:Flurothyl / Q000633:toxicity; D006439:Hemodynamics; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D009336:Necrosis; D009474:Neurons / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*; D013997:Time Factors; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: D008353:Mannitol; D005481:Flurothyl