Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network / 中华儿科杂志

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

A case of neonatal-onset type I hyperlipoproteinemia with bloody ascites / 中国当代儿科杂志

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.

Peripherally inserted central venous catheter-related thrombosis in a neonate / 中国当代儿科杂志

The female infant in this case study was admitted to the hospital 4 hours after birth due to preterm birth and respiratory distress. On the third day after birth, peripherally inserted central venous catheter (PICC) catheterization was performed. On day 42, thrombus was found at the entrance of the right atrium from the inferior vena cava during a cardiac ultrasound, and it was considered to be related to PICC placement. Low-molecular-weight heparin and urokinase were given. After two weeks of treatment, ultrasonic monitoring showed thrombus shrinkage. No bleeding or pulmonary embolism occurred during the treatment. The patient discharged after improvement. This article mainly introduces a multidisciplinary team approach to diagnosis and treatment of PICC-related thrombosis in neonates.

Neonate-onset ornithine transcarbamylase deficiency / 中国当代儿科杂志

The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.

Clinical practice of whole-genome sequencing in the rapid diagnosis of critically ill neonates / 中国当代儿科杂志

OBJECTIVES@#To explore the application of whole-genome sequencing (WGS) in the rapid clinical diagnosis of critically ill neonates.@*METHODS@#The critically ill neonates who admitted to the neonatal intensive care unit of Children's Hospital of Fudan University and underwent WGS from August to September, 2019 were enrolled in this prospective study. The genetic testing results and clinical outcome were analyzed with reference to the sequencing data and clinical features of the neonates.@*RESULTS@#A total of 15 neonates were tested, among whom there were 9 boys and 6 girls. The main reason for hospitalization included abnormal breathing in 7 neonates, poor response in 2 neonates, feeding difficulty in 2 neonates, fever in 1 neonate, hypothermia in 1 neonate, preterm birth in 1 neonate, and convulsion in 1 neonate. The mean turn-around time was 4.5 days for WGS. Finally a genetic diagnosis was obtained for 3 neonates, with a positive diagnostic rate of 20% (3/15). Among the 3 neonates, 2 neonates were withdrawn from the treatment due to severe conditions and 1 neonate died on the day when the sample was sent for genetic testing, whose etiology could be explained by the results of genetic testing.@*CONCLUSIONS@#WGS technique can provide a timely and effective diagnosis for critically ill neonates suspected of genetic diseases and provide genetic evidence for clinical treatment of critically ill cases.

Treatment of patent ductus arteriosus in very preterm infants in China / 中华儿科杂志

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

Non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t-test, rank-sum test or χ2 test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age (Z=17.62, P<0.01), lower birth weight (t=18.64, P<0.01), higher proportion of small-for-gestation age (χ2=31.06, P<0.01), multiple birth (χ²=12.82, P<0.01) and intensive resuscitation in delivery room (χ²=287.52, P<0.01), as well as lower proportion of females (χ²=10.68, P<0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P<0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P<0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.

Evaluation of the clinical effect of an artificial intelligence-assisted diagnosis and treatment system for neonatal seizures in the real world: a multicenter clinical study protocol / 中国当代儿科杂志

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.

Research advances in the clinical genetics of leukodystrophy in children / 中国当代儿科杂志

Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.

Genetic characteristics of microtia-associated syndromes in neonates / 中国当代儿科杂志

Microtia is the second most common maxillofacial birth defect in neonates and has an prevalence rate of 3.06/10 000 in China, and 20%-60% of microtia cases is associated with a certain type of syndrome. This article elaborates on the clinical phenotypes and genetic characteristics of three microtia-associated syndromes (MASs) with high prevalence, high incidence rate of ear deformity, and definite genetic etiology, i.e., oculo-auriculo-vertebral spectrum, branchio-oto-renal spectrum disorder, and Treacher-Collins syndrome, and summarizes another three common MASs, so as to provide a reference for the genetic diagnosis of neonatal MAS.

Epigenetic clocks in the pediatric population: when and why they tick? / 中华医学杂志(英文版)

Recent research efforts have provided compelling evidence of genome-wide DNA methylation alterations in pediatrics. It is currently well established that epigenetic clocks, composed of DNA methylation sites, can estimate the gestational and chronological age of cells and tissues from different ages. Also, extensive research is aimed at their correlation with early life exposure and pediatric diseases. This review aimed to systematically summarize the epigenetic clocks in the pediatric population. Publications were collected from PubMed and Web of Science databases up to Apr 2021. Epigenetic clocks, DNA methylation clocks, epigenetic age acceleration or deceleration, pediatric and the pediatric population were used as search criteria. Here, we first review the currently applicative pediatric epigenetic clocks. We then highlight the interpretation for epigenetic age deviations in the pediatric population and their association with external factors, developmental trajectories, and pediatric diseases. Considering the remaining unknown of pediatric clocks, research strategies into them are also discussed. In all, pediatric epigenetic clocks may act as potent tools to understand development, growth and diseases in early life.

Influence of coronavirus disease 2019 on the nervous system of children / 中国当代儿科杂志

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and can occur at any age, including children. Children with COVID-19 can develop the clinical symptoms of multiple systems, among which symptoms of the nervous system have been reported increasingly, and thus it is particularly important to understand COVID-19-associated neurological damage in children. This article reviews the mechanisms and types of COVID-19-associated neurological damage in children.

A review on the genetic mechanism of chromatin remodeling in children with neurodevelopmental disorders / 中国当代儿科杂志

Neural development is regulated by both external environment and internal signals, and in addition to transcription factors, epigenetic modifications also play an important role. By focusing on the genetic mechanism of ATP-dependent chromatin remodeling in children with neurodevelopmental disorders, this article elaborates on the effect of four chromatin remodeling complexes on neurogenesis and the development and maturation of neurons and neuroglial cells and introduces the clinical research advances in neurodevelopmental disorders.

Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families / 中国当代儿科杂志

This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.

Application of simulation-based medicine education in pediatric resident training / 中国实用儿科杂志

Simulation-based medicine education(SBME)refers to the clinical teaching method of using medical simulation equipment or simulator design to simulate clinical scenes,replacing the actual content of real medical scenes in an interactive way and the actual patient. Simulation is particularly important in pediatric resident training,and a large amount of evidencebased evidence confirms that simulation training used in resident training ensures patients' safety and improves patients' outcomes. The paper mainly expounds the application principle,theoretical basis,main content and the method of establishing the simulation center in the training of pediatric resident in simulated medical education,intending to promote the further development of simulation training in the training of domestic pediatric resident.

Advanced molecular technologies for the diagnosis of congenital malformation in neonates / 中国当代儿科杂志

Congenital malformation is one of the most frequent causes of infant death in western countries and major cities in China. Though genetic screening of newborns remains a hot issue and concern, the mortality rate associated with birth defects has not been significantly reduced over the past 20 years. Many genetic diseases manifest symptoms during the first 28 days of life, but full clinical symptoms might not be evident in newborns. Moreover, genetic aberrations is highly heterogeneous. These complicated factors lead to the establishment of diagnosis based on nonspecific or obscure symptoms. Recently developed array comparative genomic hybridization (CGH) and next generation sequencing (NGS) techniques with efficient high-resolution allow to screening of the entire genome for DNA copy number variants and sequencing respectively. These new and powerful tools can shorten the differential diagnosis process and quicken to movement towards targeted treatment and genetic and prognostic counseling.

Application of tetrahydrobiopterin in treatment of phenylketonuria / 中华实用儿科临床杂志

Until recently,the common treatment for phenylketonuria (PKU) was a phenylalanine (Phe)-restricted diet.Increasing evidence of suboptimal outcomes was observed in diet-treated individuals.The observation of clinically significant reductions in blood Phe levels in a subset of patients with PKU following oral administration of tetrahydrobiopterin(BH4),a cofactor of phenylalanine hydroxylase.Clinical studies suggest that treatment with BH4 provides better Phe control and increases dietary Phe tolerance,allowing significant relaxation or even discontinuation of dietary Phe restriction.The current knowledge on this novel pharmacologic approach to the treatment of PKU will be discussed.

Changes in MLS-BAEP in newborn piglets with hypoxic-ischemic brain damage during selective moderate head cooling therapy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of selective moderate head cooling therapy on maximum length sequences brainstem auditory evoked potential (MLS-BAEP) in newborn piglets with hypoxic-ischemic brain damage.</p><p><b>METHODS</b>Sixteen newborn piglets aged 5-7 day old were randomly divided into three groups: normothermic control (n=4), HI (n=6) and mild hypothermia-treated (n=6). HI was induced through temporary occlusion of both carotid arteries, followed by mechanical ventilation with low concentration of oxygen (FiO2=0.06) for 30 minutes. Mild hypothermia was induced by equipment via circulating water. MLS-BAER was recorded before HI and at 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 4 days, 7 days, 10 days, 13 days and 15 days after HI.</p><p><b>RESULTS</b>Compared with the normothermic control group, all latencies and intervals tended to increase significantly at 72 hours in the HI group and reached peak values on day 7. From day 10, all latencies and intervals tended to decrease, but apart from wave I latency, still differed significantly from those of the normothermic control group. MLS-BAER variables did not reach normal values until day 15. Ⅲ latency, Ⅰ-Ⅲ interval and Ⅰ-Ⅴ interval were significantly reduced in the hypothermia-treated group between 60 and 7 days after HI compared with the HI group (P<0.05). V latency and Ⅲ-Ⅴ interval in the hypothermia-treated group were also reduced compared with the HI group between 72 hours and 7 days after HI (P<0.05).</p><p><b>CONCLUSIONS</b>Both peripheral and central auditory systems are disturbed by HI, which shows as a significant increase in MLS-BAER variables (all latencies and intervals) in newborn piglets. Involvement in central brainstem auditory system reaches a peak on day 7 after injury. MLS-BAER variables still cannot reach to normal values until day 15. Selective moderate head cooling therapy can significantly reduce brainstem damage induced by HI.</p>

Amplitude integrated electroencephalography characteristics of normal preterm newborns: a multicenter clinical study / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the characteristics of amplitude integrated electroencephalography (aEEG) in preterm infants and changes of maturation with gestational age.</p><p><b>METHODS</b>aEEG monitoring was done within 3 days of age with domestically produced digital aEEG set (CFM3000). Duration of each recording was at least 4 hours. The continuity, sleep-wake cycle, voltage and bandwidth of all aEEG tracing were analyzed.</p><p><b>RESULTS</b>The percent of continuity background increased from 30% of 28 weeks to 85.7% of 36 weeks (χ(2) = 28.2, P = 0.026); the percent of mature sleep-wake cycle increased from 10% of 28 weeks to 100% of 36 weeks (χ(2) = 192.4, P < 0.01). Low bound voltage increased with gestational age, from (6.8 ± 1.7) µV (28 w) to 9.7 - 10.1 µV (35 - 36 w) (F = 11.4, P < 0.01). Bandwidth of the narrow band decreases gradually with gestational age, from 1.45 cm (28 w) to (0.86 ± 0.24) cm (36 w) (F = 8.731, P < 0.01). The correlation coefficient for continuity, sleep-wake cycle, low bound voltage and bandwidth of narrow band, and total scores were 0.32, 0.81, 0.38, 0.55 and 0.78 respectively (P < 0.05).</p><p><b>CONCLUSION</b>The older the gestational age of infants at birth, the more mature the aEEG pattern, manifested as increased continuity and sleep-wake cycle, the higher low bound voltage and more narrowed bandwidth with increased gestational age.</p>

Basic fibroblast growth factor stimulates the proliferation and differentiation of neural stem cells in neonatal rats after ischemic brain injury.

A little is known about the proliferation and fate of neural stem cells in the subventricular zone (SVZ) after cerebral ischemia. However, how endogenous neural stem cells are activated in the premature brain is not clear, although basic fibroblast growth factor (bFGF) is important in neurogenesis. To investigate the effect of bFGF on the proliferation and differentiation of neural stem cells after brain ischemia, we observed cellular changes in the subventricular zone (SVZ) of 3-day-old rats (approximately equivalent to premature infants) using immunofluorescence assays, Western blot analysis, and real-time quantitative PCR methods. The bilateral common carotid artery (BCCA) was occluded in 108 animals, then half received bFGF 10ng/g. Besides, 54 rats without ischemia as normal control. Proliferating cells were labeled by bromodeoxyuridine (BrdU) through intraperitoneal injection in a pulsed or a cumulative protocol. Rats were killed at 4, 7, and 14 days after ischemic injury. The number of proliferating cells in the SVZ in bFGF-treated rats was higher than that in untreated rats; bFGF also promoted neural stem cell differentiation into neurons, astrocytes, and oligodendrocytes. Western blot analysis and real-time quantitative PCR assays confirmed these results. We suggest that bFGF promotes the repair of ischemia brain injury through increasing the proliferation of neural stem cells and their differentiation into neurons, astrocytes, and oligodendrocytes.