[Expression of GRP78 and caspase-12 in neonatal rats with experimental hypoxic-ischemic white matter damage].

ABSTRACT

OBJECTIVE: GRP78 is a sensitive marker of endoplasmic reticulum stress. Caspase-12 is involved in apoptosis induced by endoplasmic reticulum stress. This study was designed to explore the changes of GRP78 and caspase-12 mRNA in neonatal rats with experimental hypoxic-ischemic white matter damage (WMD) and investigate the roles of endoplasmic reticulum stress in the WMD. METHODS: Two-day-old rats were randomized to WMD and control groups (n=49 each). The pups were sacrificed at 0, 2, 4, 6, 12, 24 and 72 hrs after hypoxia-ischemia (HI). The light microscope was used to observe the brain pathological changes. Real time PCR was used to detect the expression of GRP78 mRNA and caspase-12 mRNA in the white matter tissue. RESULTS: The expression of GRP78 mRNA began increasing 2 hrs after HI and peaked at 6 hrs in the WMD group, demonstrating significant differences at 2, 4, 6, 12, 24 and 72 hrs compared with the control group (P<0.05). The caspase-12 mRNA expression in the WMD group began increasing 6 hrs after HI and demonstrated significantly increased levels 6, 12 and 24 hrs after HI compared with those in the control group (P<0.05). CONCLUSIONS: GRP78 and caspase-12 mRNA expression increased significantly in neonatal rats with WMD. This suggests that endoplasmic reticulum stress may be induced following HI. Endoplasmic reticulum stress seems to be involved in the apoptosis of oligodendrocytes induced by HI in neonatal rats with WMD.