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J Obstet Gynaecol Res. 2005 Apr;31(2):185-91.

Expression of inducible nitric oxide synthase and cyclooxygenase-2 mRNA in brain damage induced by lipopolysaccharide and intermittent hypoxia-ischemia in neonatal rats.

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Department of Obstetrics and Gynecology, Miyazaki Medical College, University of Miyazaki, Kiyotake, Miyazaki, Japan.



The purpose of the present study was to examine the effect of lipopolysaccharide (LPS) and intermittent hypoxia-ischemia (HI) on brain damage in neonatal rats.


Seven-day-old Wistar rats were injected with saline or LPS (1 mg/kg), and then underwent left common carotid artery ligation followed by a repetitive 8% hypoxia (2.0-4.5 min) at 10-min intervals 10 times. The rats were divided into three groups: LPS with HI (LPS/HI, n = 46), saline with HI (HI alone, n = 42) and LPS alone (n = 16). Seven days later, brains were assessed for neuronal damage and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression.


Neuronal damage in the ligated side was significantly higher in LPS/HI than the other two groups (P < 0.01). The expression of iNOS and COX-2 mRNA was observed in the affected brain in LPS/HI, which corresponded well to histologic neuronal loss.


LPS enhanced intermittent HI brain damage in immature animals. The expression of iNOS and COX-2 mRNA is considered to be associated with perinatal brain injury processes.

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