Scallet A C, Binienda Z, Caputo F A, Hall S, Paule M G, Rountree R L, Schmued L, Sobotka T, Slikker W
Division of Neurotoxicology, FDA/National Center for Toxicological Research, Jefferson, AR 72079.
Brain Res. 1993 Nov 12;627(2):307-13. doi: 10.1016/0006-8993(93)90335-k.
Domoic acid is a tricarboxylic amino acid (structurally related to kainic acid and glutamic acid) that is found in the environment as a contaminant of some seafood. To determine the nature of any neurological damage caused by domoate, as well as the minimum neurotoxic dose, juvenile and adult monkeys were dosed intravenously with domoate at one of a range of doses from 0.25 to 4 mg/kg. When animals were perfused one week later, histochemical staining using a silver method to reveal degenerating axons and cell bodies showed two distinct types of hippocampal lesions. One lesion, termed 'Type A', was a small focal area of silver grains restricted to CA2 stratum lucidum, the site of greatest kainic acid receptor concentration in the brain. Type A lesions occurred over a dose range of 0.5 to 2.0 mg/kg in juvenile animals and 0.5 to 1.0 mg/kg in adult animals. No mortality occurred in any of the juvenile monkeys, but one juvenile animal that received 4.0 mg/kg sustained a second type of lesion, termed 'Type B', characterized by widespread damage to pyramidal neurons and axon terminals of CA4, CA3, CA2, CA1, and subiculum subfields of the hippocampus. Doses of more than 1.0 mg/kg in the adult monkeys either proved lethal or resulted in Type B lesions. Induction of c-fos protein had occurred in the hippocampal dentate gyrus and CA1 regions of moribund animals perfused within hours of their initial dose.(ABSTRACT TRUNCATED AT 250 WORDS)
软骨藻酸是一种三羧酸氨基酸（在结构上与 kainic 酸和谷氨酸相关），在环境中作为某些海产品的污染物被发现。为了确定由软骨藻酸盐引起的任何神经损伤的性质以及最小神经毒性剂量，对幼年和成年猴子静脉注射软骨藻酸盐，剂量范围为 0.25 至 4 mg/kg 中的一种。一周后对动物进行灌注时，使用银染法进行组织化学染色以显示退化的轴突和细胞体，结果显示出两种不同类型的海马损伤。一种损伤称为“A 型”，是局限于 CA2 透明层的一小片银粒聚集区域，该区域是大脑中 kainic 酸受体浓度最高的部位。幼年动物在 0.5 至 2.0 mg/kg 的剂量范围内出现 A 型损伤，成年动物在 0.5 至 1.0 mg/kg 的剂量范围内出现。幼年猴子均未死亡，但一只接受 4.0 mg/kg 的幼年动物出现了第二种损伤，称为“B 型”，其特征是海马体的 CA4、CA3、CA2、CA1 和下托子区域的锥体神经元和轴突终末受到广泛损伤。成年猴子中剂量超过 1.0 mg/kg 的情况要么证明是致命的，要么导致 B 型损伤。在初始给药后数小时内灌注的濒死动物的海马齿状回和 CA1 区域中发生了 c-fos 蛋白的诱导。（摘要截短至 250 字）
