Brain Underdevelopment In Fetus With Growth Restriction The Quantitative Evaluation And Antenatal Taurine Intervention

Objective1.Fetal growth restriction (FGR) is the result of various pathological factors in mother,placenta,or the fetus.FGR prevents the fetus from achieving its full growth potential.and most of FGR fetals are small for gestational age(SGA) at birth.Reduced cells number and decreased growth speed and damaged brain function in SGA fetus have been documented in recent years.However,whether FGR can cause white matter or myelin damage has not been reported. We will carry out magnetic resonance diffusion tensor imaging (MR-DTI) scan within 7 days after FGR fetus birth to detect the white matter damage.2.Inflammatory responses almost paiticipate multiple organs damagement and repairment through a series of pathological process at the abnormal conditions,such as infection and asphyxia. Protein malnutrition is one of the most common reasons for FGR.Previously,we have estamblished FGR model by feeding pragmant rats with low-protein diet,detected some underlying mechanism of brain damage and demostrated that antenatal taurine administration could improve FGR rats brain development by various mechanisms. However, wether excessive inflammation response appears FGR rats brain and wether antenatal taurine administration improves development via inhibiting the excessive inflammation response remain unknown.We will examine the level of inflamatory cytokines to test the inflammatory response in FGR brain and then observe the effects of taurine on this response process.Methods1.DTI evaluation:28 full-term SGA infants (birth weight was under 10% of the average birth weight)and 15 matched appropriate for gestational age (AGA, birth weight was between 25%-75% of the average birth weight) infants at the gestational age from 37 weeks to 40+6 weeks were enrolled in this study,who were admitted to the neonatal intensive care center of Bayi Children’s Hospital Affiliated to Beijing Military General Hospital from July 2013 to March 2014.All the neonates had no specially birth history, such as asphyxia, hypoxia-ischemic, encephalopathy, bilirubin encephalopathy, intracranial infection, periventricular leukomalacia, congenital metabolic disease and apparently injury on conventional MRI. All the infants were scanned using the 3.0 T MR scanner of GE Discovery 750 within 7 days after birth. Imaging were conducted by FSL software and tract-based spatial statistics were used to analyze the statistics. The DTI parameters fractional anisotropy(FA), mean diffusivity(MD), radial diffusivity(λ⊥), longitudinal diffusivity(λ//) between two groups were compared.and statistical analysis was conducted using SPSS 16.0 software.2.Antenatal Invention:The FGR models was established using whole-course low-protein diet.Female rats were randomly divided into FGR group, FGR+taurine group (taurine group) and control group,10 rats every group. The expression levels of TNF-α,IL-1β,IL-6 and IL-8 in fetal rats brain tissues were monitored by enzymelinkedimmunosorbentassay method, and the brains positive cells of PCNA were detected by immunohistochemistry.Results1.DTI Findings:(1)Compared with AGA group infants,the fractional anisotropy was lower,the mean diffusivity,radial diffusivity,longitudinal diffusivity were higher in SGA infants.all differences were statistically significant (P<0.05).(2)DTI were compared among the left and right hemicerebrums for the SGA group.the results show SGA infants who in same birth weight had no statistically significant between two hemicerebrums (P>0.05).(3)FA was compared between 122 brain regions of SGA and AGA groups, Corpus callosum,Internal capsule,Fornix,Anterior corona radiata(right),Stria terminalis (left), Tapetum(left),Superior longitudinal fasciculus(right),Posterior thalamic radiation ,Sagittal stratum(left),Thalamus (left), Putamen (left), Caudate nucleus (right),Cerebral peduncle,Superior fronto-occipital fasciculus,Corticospinal tract,Superior cerebellar peduncle,Middle cerebellar peduncle,Inferior cerebellar peduncle(right),Pontine crossing tract,Pons,Medial lemniscus(left),Superior frontal gyrus,Middle frontal gyrus, Inferior frontal gyrus (left),Postcentral gyrus, Superior parietal lobule(right),Cingular gyrus, Supramarginal gyrus(right),Inferior temporal gyrus(right),Insular cortex(left).(4)MD and λ//were compared between 122 brain regions of SGA and AGA groups, Cingulum hippocampal part(right),Inferior frontal gyrus(right),Lateral fronto orbital gyrus(right),Gyrus rectus(left), Parahippocampal gyrus, Hippocampus (left).(5)λ⊥was compared between 122 brain regions of SGA and AGA groups, Posterior limb of internal capsule(right),Fornix(right),Stria terminalis(right),Thalamus(right),Cerebral peduncle,Middle cerebellar peduncle (right),Inferior cerebellar peduncle (right),Medial lemniscus(left),Superior frontal gyrus(right),Middle frontal gyrus (right),Inferior frontal gyrus (right),Lateral fronto-orbital gyrus (right),Gyrus rectus (left),Parahippocampal gyrus (right).2.Effects of Antenatal Taurine:(1)Elisa:Compared with control group.The expression levels of TNF-α,IL-1β,IL-6 and IL-8 in fetal rat brain tissues were significantly increased in FGR group(P<0.05),compared with FGR group,whereas their expressions were significantly decreased in taurine group (P< 0.05).(2)Immunohistochemical:PCNA positive cells number increased significantly in FGR models compared with control group; After giving taurine antenatally, the PCNA-positive cell numbers in FGR modelfurther increased significantly (P< 0.05).Conclusion:1.FGR infants have lower value of FA and higher values of MD,XD,λ⊥,λ//of DTI parameters,suggesting that FGR can lead to part of brain white matter development delay or (and)injury.2.Prenatal supplement taurine can decrease the expression levels of TNF-α,IL-1β,IL-6 and IL-8 and increase the number of PCNA-positive cells in FGR fetal rat brain tissues,suggesting that supplement taurine could reduce the expression of pro-inflammatory cytokines,reducing inflammation injury and promoting FGR fetal brain development by inhibiting the excessive inflammation response.3.This research provides some theoretical supports for the prenatal supplement of taurine protecting FGR fetal brain.