An animal model of cerebral palsy induced by prenatal exposure to lipopolysaccharide and hypoxia

作者：Chen, Gang^*; Hu, Yanrong; Liu, Wei; Li, Jiang; Wen, Linbao; Li, Jianxin; Zhao, Lihui; Yang, Xiaopeng; Zhu, Yi; Sun, Zhenzhu; Chi, Guangming

来源：Neural Regeneration Research, 2010, 5(14): 1100-1103.

DOI：10.3969/j.issn.1673-5374.2010.14.011

• inflammation
• hypoxia
• animal model
• cerebral palsy
• periventricular leukomalacia
• brain injury
• neural regeneration

BACKGROUND: Neonatal cerebral palsy is mainly caused by prenatal factors. At present, an animal model of prenatal infection and early postnatal hypoxia does not exist.
OBJECTIVE: To observe morphology and motor performance following prenatal infection and hypoxic insult-induced brain damage of neonatal rats to verify the feasibility to establish a model of cerebral palsy.
DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratories of Xinjiang Center for Disease Control and Prevention from September 2007 to June 2008.
MATERIALS: The hypoxic incubator was purchased from Shanghai Pediatric Medical Institute, China. Lipopolysaccharide (LPS, Escherichia coli, O55: B5) was purchased from Sigma-Aldrich (St. Louis, MO, USA).
METHODS: A total of 27 Wistar rats, aged 7 days, were randomly assigned to sham-surgery group (n = 15) with no carotid artery incision or hypoxia treatment, hypoxia/ischemia (H/I) group (n = 12) undergoing ligature of the right common carotid artery followed by exposure to hypoxia at postnatal day 7 (P7), and LPS/H group (n = 19), in which pregnant rats were exposed in utero to LPS followed by prenatal hypoxia at embryonic day 16.
MAIN OUTCOME MEASURES: Behavior, compound muscle action potential, and pathological changes were observed in 28-day-old rats.
RESULTS: The footprint repeat space showed that left limb footprint repeatability in the H/I and LPS/H groups was lower than in the sham-surgery group (P < 0.05). The space between the footprints was larger and unstable. Hind limb quadricep compound muscle action potential in the H/I and LPS/H groups showed lower wave amplitude compared with the sham-surgery group (P < 0.05). Hematoxylin and eosin staining showed irregular cells around the ventricle, as well as periventricular leukomalacia.
CONCLUSION: An animal model of cerebral palsy was established, which simulated the human condition most likely associated with occurrence of this disease. This model could be used for experimental studies related to cerebral palsy.

• 出版日期2010-7-30
• 单位新疆维吾尔自治区人民医院