Neurobehavioral Function Research Of Excitotoxic Brain Damage In Neonatal Mice

Objectives The study was designed to investigate a reproducible,standardized method for short- and long-term neurobehavioral functionassessment in mice subjected to excitotoxic brain damage and to explorea new experimental method for study neuroprotection of perinatal brainlesions.Methods 61 five-days old and ICR-type neonatal mice coming form differentdams were selected and divided into three groups randomly: empty control,saline control and experimental groups. Behavior changes of excitotoxicbrain damage model mice were observed with double-blind method includingsurface righting reflex (P6, P7, P8, P9, P10), swimming development(P8,P10, P12), open field behavior(P30, P31, P32) and Y-maze discriminationlearning experiment(P33, P34).Meanwhile, body weight was observed duringthe whole period. The brains of mice in the saline control and experimentalgroups were sacrificied and dislodged for consecutive sections andhistological hematoxylin and eosin staining and calculating the diameterof the brain damage.Results 1. Body weights of the mice in the experimental group mice were decreased significantly(P＜0.05)except P5 and P6. There were nodifference between empty control group and saline control group(P＞0.05);2. Surface righting reflex Righting times of experimental groupmice(2.12±0.61,1.86±0.65,1.50±0.51,1.28±0.29,1.01±0.15)wereincreased significantly(P＜0.05). There were no difference between emptycontrol group and saline control group(P＞0.05). Righting time ofexperimental group mice were gradually more and more close to controlgroup; 3. Swimming scores of mice in the experimental group mice(6.33±0.98, 6.87±0.74, 7.13±0.64)were decreased significantly compared withthat of the control group (P＜0.05). There were no difference betweenempty control group and saline control group(P＞0.05). Swimming scoresof experimental group mice increased gradually close to the control grouplevels. There were no difference of the scores between control andexperimental groups of paddling(usage of limbs)scores(P＞0.05) andpaddling scores in P10 and P12 were 2.00. Only P10 swimming directionscores(2.40±0.51)of experimental group mice were decreasedsignificantly compared with that of the control group(P＜0.05). Therewere no difference between empty control and saline control groups(P＞0.05). Body angle(head position)scores of experimental group mice(2.27±0.46,2.53±0.52,2.53±0.52) were decreased significantly(P＜0.05).There were no difference between empty control group and Saline controlgroup(P＞0.05)and body angle scores in P12 were 3.00;4. There were nodifference between control and experimental groups of open field behaviorexperimental (P＞0.05)except grooming behavior in P30(F=4.179, P=0.021).There were no difference between empty control and saline control groups(P＞0.05);5. Learning times of experimental group mice was(19.79±2.42)decreased significantly (F=10.477, P=0.000). There were nodifference between empty control and saline control groups(P＞0.05). Right reaction rate of empty control group,saline control group and experimental group was 96.50%, 95.00% and 86.67%; Right reaction rateof empty control group significant decreased (x²=14.703, P=0.001). Therewere no difference between empty control and saline control groups(x²=0.553, P=0.311). 6. Histological section of experimental group canobserved cysts lesion of right cerebral hemisphere white matter(Thediameter of cysts lesion is 1008.00μm(P₂₅=816.00μm, P₇₅=1152.00μm).There were no white matter lesions in saline control group micebrain;7. There is asignificant correlation between the diameters of thebrain damage and righting time in P10 (r=0.609, P=0.016)or swimming scoresim P8 (r=0.602, P=0.017). There is no correlation between the diametersof the brain damage and other righting times or swimming scores and thereis no correlation between the diameters of the brain damage and learningand memory result too.Conclusions 1. Neonatal mice short-term developmental reflexes behaviorsand long-term learning and memory function were impaired afterexcitotoxic brain damage; 2. Surface righting reflex, swimmingdevelopment and Y-maze discrimination learning experiment can be usedto short-term developmental reflexes behaviors and long-term behaviorchange of excitotoxic brain damage mice; 3. The results of short-termdevelopmental reflexes behaviors, surface righting reflex result in P10and swimming development result in P8, can predicts long-tern anatomicextent of cerebral injury in neonatal mice excitotoxic damage model.