Wa. Kofke et al., SUBSTANTIA-NIGRA DAMAGE AFTER FLUROTHYL-INDUCED SEIZURES IN RATS WORSENS AFTER POSTSEIZURE RECOVERY - NO EXACERBATION WITH HYPERGLYCEMIA, Neurological research, 15(5), 1993, pp. 333-338
The substantia nigra pars reticularis (SNPR) of rats is highly suscept
ible to both seizure- and ischaemia-mediated damage. Hyperglycaemic ex
acerbation of brain damage similar to that observed after global brain
ischaemia may also occur in rats with status epilepticus. We tested t
he hypotheses that hyperglycaemia exacerbates seizure-induced SNPR dam
age in rats and that SNPR lesions develop rapidly post-seizure. Haloth
ane-anaesthetized, paralysed, and mechanically ventilated rats were pr
epared for haemodynamic and EEG monitoring. Halothane was discontinued
, and mechanical ventilation on 30% oxygen/70% nitrous oxide was conti
nued for 1 h. Three treatment groups (20 rats each) were studied. (1)
control lactated Ringer's solution; (2) equiosmolar control, 40% manni
tol; and (3) hyperglycaemia, 50% dextrose. Infusions were started 5 mi
n before seizures were induced with flurothyl 3% administered for eith
er 45 (n = 10) or 75 (n = 10) min. Immediately after seizures, half of
the animals underwent cerebral perfusion-fixation with formalin and h
alf were allowed to recover for 2 h post-seizure and then perfused. Br
ain 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 s
cores: control, eosinophilic neurons = 3.6, vacuolation = 4.0; hypergl
ycaemia, eosinophilic neurons = 3.0, vacuolation = 2.75, p < 0.05). SN
PR damage was worse after 2 h of recovery (pathology scores: 0 h recov
ery, eosinophilic neurons = 0.9, vacuolation = 0.1; 2 h recovery, eosi
nophilic neurons = 3.9, vacuolation = 3.8; p < 0.05). Hyperglycaemia d
id not exacerbate flurothyl-seizure-induced SNPR damage, and maturatio
n of the lesions was observed at 2 h post-seizure.