The Dynamic Study Of Plasma Brain-Derived Neurotrophic Factor, S100B Protein And Tau Protein In Fullterm Newborns With Perinatal Asphyxia

Objective: Perinatal asphyxia and Hypoxic ischemic encephalopathy (HIE) are the conmom cause of mortality and morbidity in term newborns, The general incidence of perinatal asphyxia is 7%～10% according to some study reseach. Detecting speicial biochemical indicators is bound to play an important role in evaluating the severity after brain injury. Brain derived neurotrophic factor(BDNF), widely expressed in the central nervous system, plays an impointant part in reparing and regenerating the neuron. Animal experiments already confirmed that the expressing of BDNF significantly increased after hypoxia-ischemia. S-100B protein, as an active form in S100 protein family in the central nervous system, has the brain tissue specificity, Serum S-100 protein will be increased, in result of releasing into blood circulation passing through blood-brain barrier when brain damage ocurred. Study demonstratd the expression of Tau protein dramaticlly increased in the acute brain ischemia, It is supposed that Tau protein may be the sensitive index in the early stage of brain demage. However, the three biochemical indexes talked above had been seldom reported in study research so far. The present dynamic study aimed at assessment of radial veins BDNF, S100B protein and Tau protein level at differernt times in the term newborns with perinatal asphyxia, as markers of central nervous system injury and predictors of severity of HIE, with following up of their levels during the reperfusion phase, providing effective diagnostic markers. Try to find the relationship between their levels and the severity of HIE, in order to decrease the mortality and morbidity in term babys with perinatal asphyxia. Methods:1 Subjects This prospective case-control study, conducted in Neonatal Intensive Care Unit at Bethun International Peace Hospital, over a period of one year from June 2008 till June 2009, included 30 cases and 20 healthy controls during the same period. An inform verbal consent was obtained from the parents before enrollment of patients.1.1 Cases: Newborns included in this study were full term infants, the gestation≥37weeks and the birth weight≥2500g, meanwhiles satisfied two of the conditions below:1) Apagar score<3 at 1 min or≤5 at 5 min;2) Arterial blood gas test pH<7.0 just after birth with base defecit≤-10mmol/L;3) The presence of postnatal clinical complications attributed to perinatal asphyxia, such as neurological manifestations, multiorgan failure, hypotension requiring inotropic support, severe apnea and oliguria.Fullterm newborns with congenital malformations, chromosomal abnormalities, suspected inborn error of metabolism, congenital heart disease, blood group incompatibility, sepsis, diabetic or preeclamptic toxemia mothers and those with multiple gestations were excluded from the study. 1.2 Controls: It concluded 20 term apparently healthy newborns appropriate for gestationgal age without signs of perinatl asphyxia.Gestational age and sex matched with the study group with no signs of fetal distress, arterial blood gas tests pH>7.2, Apagar score >7 at 1and 5 minutes.1.3 Gestational age, birth weight, delivery mode, clinical manifestation and sex distribution were recorded, Neonatal Neurologic Behavioral Assessment at 7th day, ultrasound or CT brain were done.2 Sample Test2.1 Sample collection: blood samples were collected from radial arterial of all cases in 24 hours, 72 hours and 7 days after birth, then divided into dry tubes, centrifuged 5 minutes with 3000r/min and separated plasma into 3-5 tubes, stored at -70℃for assessment of BDNF, S100B protein, Tau-protein.2.2 Test methods: Plasma levels of the three factors in the sample were detected by ELISA technique using Quantikine hunman BDNF kit by R and D systems, S100B kit by GBD systems and YuBo biologichnology company in Shanghai.2.3 Statistical analysis: SPSS13.0 statistics software was used to carry on statistics processing, Qauntitiative variables were describled as Mean±SD, T-test was used when normal distribution measurement data was content,Analysis of variance was used to examinate the diference among markers by the repeated measurement; Kruska Willis tests was used to compare non parametiric data. Chi-Square was used to compare categorical variables. P-value<0.05(double side) had statistical significance, highly significant when p-vale<0.01.Results:1 There was no statistical difference among the two groups for gestational age, birth weight, postnatal age, delivery mode and sex distribution (P>0.05).2 The present study checked out2.1 BDNF level of healthy neonates was 713.01±259.40pg/ml at 3th day after brith, the S100B protein level was 1.44±0.21μg/L, Tau protein was 1.11±0.46ng/ml. The levels of serum BDNF, S100B, Tau protein were: 1211.02±480.00 pg/ml, 1.85±0.70μg/L, 1.11±0.46pg/L.The level of BDNF was confirmed the level siginificantly increased in 24h of postnatal life comparing to the controls in our study (p<0.01).2.2 The dynamic study confirmed, the level of serum BDNF increased in the first 24 hour of postnatal life, the level of plasma BDNF decreased at 3th day, increased again at 7th day, had no statistical discrepancy. While the level of S100B protein had a progressive increased tendency in 24h, 72h, 7day of postnatal life( p<0.01), Tau protein had no statistical discrepancy (P>0.05).2.3 There was dramatic difference in both of plasma BDNF and S100B protein at 7th day between moderate-severe HIE cases and mild HIE patients (p<0.05). Tau protein level had no difference in different times. Conclusions:BDNF level siginificantly increased after 24 hours in term newborns with perinatl asphyxia, S100B protein sustained a high level during 7days after birth, both of them were detected increased dramatically between mild and moderate-severe HIE cases at 7th day in our study. Plasma BDNF in coordination with the level of S100B protein as an effective maker, was probable to do an early diagnosis the severity of brain damage. When brain damage occurred, we could detect the level of BDNF in the early stage. Serum BDNF and S100B protein may be used as a predictor of the severity and outcome of perinatal asphyxia.