Moncada C, Arvin B, Le Peillet E, Meldrum B S
Department of Neurology, Institute of Psychiatry, London, U.K.
Neurosci Lett. 1991 Dec 9;133(2):287-90. doi: 10.1016/0304-3940(91)90590-p.
Single focal injection of the excitatory amino acids (EAAs) kainic acid (KA, 1.1 nmol/microliters) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S)-AMPA, 6 nmol/microliters) into rat dorsal hippocampus resulted in widespread neurodegeneration with 90-100% loss of hippocampal pyramidal cells in CA1, CA2, CA3 and CA4 subfields, and 50-70% loss of dentate granule (DG) cells. Focal injection of NMDA (30 nmol/microliters) under the same conditions resulted in 70-90% loss of CA1 cells with less damage in CA2, CA3, CA4 and DG cells (30-50%, 10-30%, and 30-50%, respectively). The non-NMDA antagonists NBQX (2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f) quinoxaline) and GYKI 52466 (1-(amino)phenyl-4-methyl-7,8-methylendioxy-5H-2,3,benzodiazepine. HCl) co-injected (24 nmol/microliters) with EAAs or given as i.v. infusion (30 mg/kg/3h), protected against KA toxicity in CA1, CA2 and DG cells, with no protection in CA3 and CA4. NBQX i.v. protected against (S)-AMPA toxicity in the DG cells but no protection was observed against (S)-AMPA toxicity in hippocampal subfields (CA1, CA2 and CA4). Intravenous administration of NBQX and GYKI 52466 (30 mg/kg/3 h) also failed to protect against NMDA toxicity in the hippocampus. Systemic injections of D(-)-CPPene, (E)-4-(3-phos-phonoprop-2-enyl)-piperazine-2-carboxylic acid, (10 and 5 mg/kg, i.p., 20 min prior and 3 h post EAA injection) protected against NMDA and KA toxicity in the CA1, CA2 and DG subfield with no protective effect against (S)-AMPA toxicity.
将兴奋性氨基酸（EAAs）海藻酸（KA，1.1纳摩尔/微升）和（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（S）-AMPA（6纳摩尔/微升）单次局部注射到大鼠背侧海马体中，导致广泛的神经变性，CA1、CA2、CA3和CA4亚区海马锥体细胞损失90 - 100%，齿状颗粒（DG）细胞损失50 - 70%。在相同条件下局部注射NMDA（30纳摩尔/微升）导致CA1细胞损失70 - 90%，而CA2、CA3、CA4和DG细胞损伤较小（分别为30 - 50%、10 - 30%和30 - 50%）。非NMDA拮抗剂NBQX（2,3-二氢-6-硝基-7-磺酰氨基-苯并[f]喹喔啉）和GYKI 52466（1-（氨基）苯基-4-甲基-7,8-亚甲基二氧基-5H-2,3-苯并二氮杂卓盐酸盐）与EAAs共同注射（24纳摩尔/微升）或静脉输注（30毫克/千克/3小时），可保护CA1、CA2和DG细胞免受KA毒性影响，但对CA3和CA4无保护作用。静脉注射NBQX可保护DG细胞免受（S）-AMPA毒性影响，但未观察到对海马亚区（CA1、CA2和CA4）（S）-AMPA毒性的保护作用。静脉注射NBQX和GYKI 52466（30毫克/千克/3小时）也未能保护海马体免受NMDA毒性影响。全身注射D（-）-CPPene，（E）-4-（3-膦酰基丙-2-烯基）-哌嗪-2-羧酸（10和5毫克/千克，腹腔注射，在EAA注射前20分钟和注射后3小时）可保护CA1、CA2和DG亚区免受NMDA和KA毒性影响，但对（S）-AMPA毒性无保护作用。
