Systemic administration of domoic acid-induced spinal cord lesions in neonatal rats.
Domoic acid (Dom) is a glutamate analog and a seafood toxin that has caused neurological disturbance and death in humans. Brain lesions caused by Dom have been documented in the literature, but the effect of Dom on the spinal cord has not been investigated as extensively. Systemic administration of glutamate agonists (i.e., homocysteate, kainate, and a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) caused spinal cord lesions in infant rats. In the present study, the toxic effects of Dom on the developing spinal cord are examined. Neonatal rats on Postnatal Day 7 were administered Dom subcutaneously at doses of 0.10, 0.17, 0.25, 0.33, 0.42, and 0.50 mg/kg, respectively. Motor seizures characterized by scratching, tail flicking, and swimming-like movement were induced by Dom at all doses. High doses of Dom (> or = 0.33 mg/kg) further induced a hindlimb paralysis, a forelimb tremor, and death that occurred in less than 2 hours. The percentages of death and paralysis induced by 0.33 mg/kg Dom were 47% and 65%, respectively (n = 17). At this dose, electrocorticogram was recorded and synchronized interrupted electrical activities in brains of these animals were detected. However, no brain damage was detected in these rats. Spinal cord lesions characterized by focal hemorrhage, neuronal swelling, and neuronal vacuolization were found in 73% of the animals that had shown the paralysis/tremor in their extremities, as examined 1 to 2 hours after Dom injection. These lesions were seen at all spinal cord levels. Neuronal degeneration was mainly found in the ventral and intermediate gray matter, whereas cells in the dorsal portion of the spinal cord were relatively spared. Data suggest that observed behavioral changes were due to spinal cord damage rather than seizures or brain lesions.
Wang
G J
GJ
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, USA.
Schmued
L C
LC
Andrews
A M
AM
Scallet
A C
AC
Slikker
W
W
Binienda
Z
Z
D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005121:Extremities / Q000294:innervation; D007279:Injections, Subcutaneous; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009467:Neuromuscular Depolarizing Agents / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010243:Paralysis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D014202:Tremor / Q000139:chemically induced / Q000473:pathology
D009467:Neuromuscular Depolarizing Agents; D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid