The effects of propofol on neurotoxicity induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid in rat mixed cortical cultures.

Seo,  Myoung Sin; Park,  Sung Yong; Kim,  Kye Sook; Moon,  Bong Ki; Kim,  Jin Soo; Lee,  Sook Young

doi:2008.55.5.607

Korean J Anesthesiol > Volume 55(5); 2008 > Article

Original Article

Korean Journal of Anesthesiology 2008;55(5):607-612.
DOI: https://doi.org/10.4097/kjae.2008.55.5.607

The effects of propofol on neurotoxicity induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid in rat mixed cortical cultures.

Myoung Sin Seo, Sung Yong Park, Kye Sook Kim, Bong Ki Moon, Jin Soo Kim, Sook Young Lee

Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Korea. anesylee@ajou.ac.kr

Abstract

BACKGROUND
The pattern of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated neurotoxicity (necrosis vs apoptosis) and the neuroprotective effect of propofol on AMPA-mediated neurotoxicity are still unclear.
METHODS
Thirteen-day-old primary rat mixed cortical cultures were used. To measure the neuroprotective effect of propofol, AMPA (50micrometer), AMPA (50micrometer) plus propofol (0.1, 1, 25, 50micrometer), AMPA (50micrometer) plus DMSO, propofol (50micrometer) and DMSO were administered (n = 45). Seventy-two h later, surviving cells were counted using trypan blue staining and were converted to cell death rate (CDR). To measure the effect of propofol (50micrometer) on AMPA (50micrometer)-induced apoptosis, a triple stain was done. In a fixed field (x400), the number of neuronal cells stained by neuronal nuclei (NeuN) and Hoechst staining and apoptotic cells stained by terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL) assays were counted. Apoptotic cell rates (ACR) were also calculated. Statistical analyses were performed using one way-analysis of variance followed by Bonferroni's test. P < 0.05 was considered statistically significant.
RESULTS
AMPA (50micrometer) stimulation demonstrated 49.3% CDR, and adding propofol 50micrometer decreased CDR to 29.4% (P < 0.05). In the TUNEL assay, cells with no drug treatment demonstrated 12.3% ACR and 50micrometer AMPA increased ACR to 28% (P < 0.05). Adding 50micrometer propofol to AMPA decreased the ACR to 20.1% (P < 0.05).
CONCLUSIONS
Propofol (50micrometer) had neuroprotective effects against AMPA (50micrometer)-induced cell death by reducing apoptosis.

Key Words: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; apoptosis; propofol