Abstract:

BACKGROUND: At present, studies about cerebral palsy models mainly focus on fetal distress, perinatal hypoxia-ischemia, bilirubin encephalopathy and infection; however, there is no obvious brain damage sequela. Combined fetal exposure to lipopolysaccharide and early neonatal hypoxia/ischemia is a new way to construct cerebral palsy models.
OBJECTIVE: To construct a novel type of cerebral palsy model in rats induced by intrauterine infection at late pregnancy and hypoxia combined with sequential hypoxia-ischemia and to evaluate the advantages of this model.
METHODS: All pregnant rats and their later offspring were divided into experimental group 1, experimental group 2 and control group. The pregnant rats were injected with lipopolysaccharide (i.p.) in the experimental groups and normal saline in the control group every two days, from pregnant day 16 until delivery. Four hours after injection, the experimental groups were exposed to O2/N2 mixture for 2.5 hours. On postnatal day 7, bilateral common carotid arteries were ligated in the experimental group 1. On postnatal days 14 and 28, immature rats in the three groups were tested by weight, crawling ladder, modified neurological severity scores and open-field test and pathological section.
RESULTS AND CONCLUSION: In the experimental group 1, the body mass was significantly lower than that in the other two groups (P < 0.01), and the number of drop down in crawling ladder test and modified neurological severity scores were significantly higher than that in the other two groups (P < 0.05, P < 0.01). The distance in crawling ladder test and open field test was the shortest in the experimental group 1 at day 28. The rats in the experimental group 1 showed slow growth and development, instable muscle force and delayed reflection (P < 0.05). Neurons in the gray matter arranged in disorder, the white matter became thinner and inflammatory cells infiltrated. The rats in the experimental group 2 were not as serious as those in the experimental group 1. These findings indicate that, in late pregnancy, intraperitoneal injection of lipopolysaccharide and hypoxia with postnatal bilateral common carotid artery ligation can build a new stable rat model of cerebral palsy.