A clinically relevant model of perinatal global ischemic brain damage in rats

作者：Yang Ting; Zhuang Lei; Terrando Niccolo; Wu Xinmin; Jonhson Mark R; Maze Mervyn; Ma Daqing^*

来源：Brain Research, 2011, 1383: 317-323.

DOI：10.1016/j.brainres.2011.01.081

• Perinatal asphyxia
• Hypoxic/ischemic brain injury
• Apoptosis
• TUNEL
• Morris water maze

We have designed a clinically relevant model of perinatal asphyxia providing intrapartum hypoxia in rats. On gestation day 22 SD rats were anesthetized and the uterine horns were exteriorized and placed in a water bath at 37 degrees C for up to 20 min. After this, pups were delivered from the uterus and manually stimulated to initiate breathing in an incubator at 37 degrees C for 1 h in air. Brains were harvested and stained with cresyl violet, caspase-3, and TUNEL to detect morphological and apoptotic changes on postnatal days (PND) 1, 3, and 7. Separate cohorts were maintained until PND 50 and tested for learning and memory using Morris water maze (WM). Survival rate was decreased with longer hypoxic time, and 100% mortality was noted when hypoxia time was beyond 18 min. Apoptosis was increased with the duration of hypoxia with neuronal loss and cell shrinkage in the CA1 of hippocampus. The time taken for the juveniles to locate the hidden platform during WM was increased in animals subjected to hypmda. These data demonstrate that perinatal ischemic injury leads to neuronal death in the hippocampus and long-lasting cognitive dysfunction. This model mimics hypoxic ischemic encephalopathy in humans and may be appropriate for investigating therapeutic interventions.

• 出版日期2011-4-6
• 单位北京大学