| Autor: |
Izumisawa, Nobuyuki, Kawakami, Akio, Ohata, Takeji, Hanada, Takanori, Okeda, Riki |
| Zdroj: |
Experimental Neurology; August 1995, Vol. 134 Issue: 2 p199-204, 6p |
| Abstrakt: |
The neuroprotective properties of glutamate receptor antagonists arise from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids. However, J. W. Olney et al.(1989, Science224: 1360-1362) have reported that MK-801, an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, induced morphological damage in neurons in the cerebral cortex of rats. YM90K is a potent α-amino-3-hydroxy-5-methylisoxazole propionic acid receptor antagonist which has high neuroprotective efficacy against delayed neuronal injury. The purpose of this study was to investigate whether YM90K induces a vacuolar reaction in the cytoplasm of neurons similar to that seen after the administration of MK-801. All experiments were performed on female F344 rats. YM90K was administered by iv infusion for 3 h at the dose of 40 mg/kg/h. MK-801 was given by single sc injection at the dose of 1 mg/kg. All rats receiving MK-801 showed neuronal vacuolation. The affected neurons were recognized as medium-sized pyramidal-shaped neurons which were distributed between layers II and IV in the posterior cingulate and retrosplenial neocortices. Most of these vacuoles contained multiple small and round structures that appeared to be remnants of mitochondria. Other vacuoles were recognized as enlarged sER or those present within the bilaminar nuclear membrane. MK-801 also induced heat shock protein immunoreactivity in the same neurons. In contrast, no such pathomorphological changes could be detected in the YM90K-treated rats. The present results as well as recent reports that some NMDA receptor antagonists, including SL 82.0715 and L 687,414, which have different sites of action, did not induce these alterations suggest that the neurotoxicity of glutamates antagonists may be related to the receptor subtype with which they interact or the active site of each compound. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full Text from ScienceDirect