| Objective Perinatal brain injury in premature newborns has a high risk of future behavior and neurological deficits. Many investigators have focused on morphological, biochemical changes associated with hypoxic-ischemic brain insult, but the behavioral and cognitive alteration of the animal after insult are also necessary. The aim of the present study is to investigate the pathologic changes in white matter of 3-day-old rats subjected to bilateral ligation of the common carotid artery and evaluate the development of neurological reflexes, motor and cognition till they grow up and find the relationship between them.Methods The present study was conducted to employ 3rd days SD premature rats 30 clutchs (360 rats). Rats were randomly divided into a experimental group and a control group according a random number table. Bilateral carotid ligation was used to perform premature brain damage in the experimental group. We used electron microscope, HE staining, premature oligodendrocyte marker O4, and TUNEL double immunofluorescence staining, MBP immunohistochemistry ways to investigate the pathologic manifestation, apoptosis of oligodendrocyte, express of myelin related protein. Examinations of neurobehavioral development were started postnatal day 7 and carried out daily until postnatal day 21. Inspections were made for maturation of physical characteristics such as weight, eye opening, incisor eruption and ear unfolding. Pups were tested for neurological reflexes such as sensory reflexes,righting reflexes,negative geotaxis,limb placing, grasp reflexes and Gait reflex. Motor test were carried out twice a week since rats 3 weeks to 6 weeks after birth., such as foot fault test, vertical screen test, traversing a square bridge and rotarod test. Morris water mase test was made every two weeks for cognition evaluation at rats 7 week to 13 weeks after birth.Results①The survival rate of control groups is 100% (120/120), experimental groups 51.25% (123/240). 87.8% (108/123) of pups in experimental groups had disorders in the development of eyes.②The aviary weight of brains in experimental groups was 1.06g±0.02g at 21days after birth and 1.46g±0.04g in control groups, P＜0.01.③We observed that the oligodendrocyte turned to be dropsical in experimental groups at 6h after surgery. Most of organelle were dropsical, such as mitochondrion,endoplasmic reticulum,Golgi apparatus. The amount of mitochondrion decreased than control group. We also observed that some mitochondrion had vacuolus and some rough endoplasmic reticulums were degranulated. The chromatin of the oligodendrocyte nucleus distributed uneven and a few cells showed karyopycnosis in experimental groups at 12h after surgery. The oligodendrocyte generally showed karyopycnosis in experimental groups at 24h after surgery.④Pathologic changes of white matter injury showed rarefaction, liquefaction and microglia hyperplasia. Most of apoptotic cells are premature oligodendrocyte with marker O4. The express of myelin related protein also had obvious reduction.⑤The time was delated in experimental groups in eye opening, startle reflex, negative geotaxis, limp placing and grasping reflex (p＜0.05). The rats of experimental groups showed bad motor endurance capacity,poor motor coordination capacity and equilibrant. The Morris water maze test showed that the rats of experimental groups had spatial and memory cognition defect.Conclusions①The early pathologic changes of premature rats with hypoxic ischemic brain damage were cell apoptosis and diffused white matter injury, and later showed ventriculomegaly and softening focus.②The somatic growth of rats were retarded in experimental groups. Their eyes were damaged and several neurological reflexes were inhibited. The motor ability of rats can be compensated in experimental groups, then decreased with development.③The rats of experimental groups showed bad motor endurance capacity, poor motor coordination capacity and equilibrant when the rats were in their childhood.④The Morris water maze test showed that the rats of experimental groups had spatial and memory cognition defect when the rats in their adolescent.⑤The study provided us evidence and help us to understand the pathologic change of premature infants progressively with the neurobehavioral and motor changes.
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