Diagnosis model of the white matter injury of premature infants based on ultrasonography radiomics / 中华超声影像学杂志

Objective:To investigate the value of the ultrasonography in the diagnosis of the white matter injury of premature infants based on gray-scale ultrasonography radiomics.Methods:A total of 256 premature infants in Huazhong University of Science and Technology Union Shenzhen Hospital and Shenzhen Hospital of Southern Medical University from August 2018 to April 2022 were analyzed retrospectively. The computer-generated random numbers were assigned to the training set and the verification set according to 6∶4 ratio. On the basis of standardized collection of craniocerebral ultrasound images, the radiomics features were extracted from imaging by Pyradiomics 3.0.1 software package, the Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) and stepwise regression were used to select the optimal features. Then the Logistic regression was used to build radiomics model. According to MRI, ROC curve was utilized to evaluate the performance of the model. The craniocerebral ultrasound images in the validation set were independently diagnosed by a senior physician and a junior physician, and then the above two physicians diagnosed again with the help of the radiomics, and the diagnostic abilities of this model were compared with those of the junior and senior physicians with and without radiomics assist. Results:A total of 5 optimal features were selected to develop radiomics model. The sensitivity, specificity, accuracy and the area under the ROC curve (AUC) in the training and validation sets were 0.861, 0.775, 0.799, 0.818; 0.929, 0.824, 0.853, 0.876, respectively. The sensitivity, specificity, accuracy and AUC in the senior sonographer, the junior sonographer, and both of them with radiomics assist for the dagnosis in the validation set were 0.929, 0.892, 0.902, 0.910; 0.714, 0.743, 0.735, 0.729; 0.929, 0.919, 0.922, 0.924; 0.857, 0.824, 0.833, 0.841, respectively. Performance of radiomics model reached the level of the senior sonographer (AUC: 0.876 vs 0.910, P=0.284), which was significantly better than the performance of the junior sonographer(AUC: 0.876 vs 0.729, P=0.001). Performance of the junior sonographer with radiomics assist was significantly better than the performance of the junior sonographer(AUC: 0.841 vs 0.729, P=0.003). Performance of the senior sonographer with radiomics assist was comparable to that of the senior sonographer(AUC: 0.924 vs 0.910, P=0.156). Conclusions:The ultrasound diagnosis method based on radiomics technology shows good diagnostic performance for the white matter injury of premature infants. It is helpful to improve the diagnostic ability of junior sonographer. It is expected to assist the sonographers in diagnosis and provide objective, consistent and accurate results for clinical practice.

Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Progress of microbiota-gut-brain axis in the pathogenesis of white matter injury in preterm infants / 国际儿科学杂志

White matter injury in preterm infants is a unique form of brain injury.It is one of the most common cause of chronic neurological diseases such as cerebral palsy and various neurobehavioral disorders.Perinatal infection, inflammation and hypoxic ischemia are related to the pathophysiology of white matter injury in preterm infants.Signals released by the gut microbiota, such as microbial metabolites, can modulate inflammatory and immune responses characterized by microglial activation, and ultimately it affects the differentiation of premyelin oligodendrocytes and causes white matter injury in preterm infants.Recently more attention has been paid to the role of gut microbiota in the pathogenesis of white matter injury in preterm infants.This article reviews the progress of "microbiota-gut-brain axis" involved in the pathogenesis of white matter injury in preterm infants, so as to provide reference for further prevention and treatment of white matter injury.

White matter injury exacerbated anxiety-like behavior of db/db mice after distal middle cerebral artery occlusion / 中国医师进修杂志

Objective:To explore the possible mechanism of exacerbation of anxiety-like behavior in db/db mice after distal middle cerebral artery occlusion (dMCAO).Methods:The db/db mice was used to establish a type 2 diabetes mellitus model. Meanwhile, heterozygous db/+ mice and C57 wild-type (WT) mice were chosen as double control groups. Then a permanent distal middle cerebral artery occlusion model was employed as an acute ischemic stroke model. The blood glucose levels before and post-dMCAO surgery on day1, day3, and day5 were detected. The brain tissue loss at 35 days after stroke was measured by immunofluorescent staining of MAP2. The open-field test was performed to estimate anxiety-like behavior and general motor and exploring ability of the animals. Axons and myelin were immunostained with non-phosphorylated neurofilaments (SMI32) and myelin basic protein (MBP), respectively, to evaluate differences in white matter integrity in WT, db/+ and db/db mice 35 days after stroke. The correlation between SMI32/MBP and open field test parameters (time in center and corner) was analyzed. Flow cytometry was employed to detect the amount of T cells and B cells, including regulatory T cells (Tregs) in the brain tissue.Results:Blood glucose levels in db/db mice were significantly higher than db/+ mice and WT mice in both sham and dMCAO groups ( P<0.01). There was no significant difference in brain tissue loss 35 days post-stroke among db/db mice, db/+ mice, and WT mice. In the open field test, there were significant differences in the total distance of db/db mice, db/+ and WT mice in the sham and dMCAO groups. Db/db mice shorter than db/+ mice ( P<0.05), WT mice ( P<0.01), and db/+ mice shorter than WT mice ( P<0.05). There were significant time differences in the center among db/db, db/+, and WT mice in sham and dMCAO groups. In both the sham and dMCAO groups, db/db mice spent less time in the center area of the open field than WT mice ( P<0.01). In the sham group, db/+ mice spent less time in the center area than WT mice ( P<0.05). In dMCAO group, db/db mice spent less time in the center area than db/+mice ( P<0.05), and db/+ mice spent less time in the center area than WT mice ( P<0.01). For the time in the corner, in both the sham and dMCAO groups, db/db mice and db/+ mice consumed more time than WT mice ( P<0.01 or <0.05). In the dMCAO group, db/db mice spent more time in the corner than db/+ mice ( P<0.05). Referring to white matter injury, an increased SMI32/MBP ratio in EC area and CTX area (data was not shown in this article) after dMCAO in db/db, db/+ and WT mice were detected. In EC area, db/db mice have a higher SMI32 ratio than db/+ mice and WT mice: 4.24 ± 0.37 vs. 1.96 ± 0.37, 1.80 ± 0.36, both have significant differences ( P<0.01). For db/db mice and WT mice, the SMI32/MBP ratio negatively correlates with time in center and positive correlation with time in the corner. Three days after dMCAO, the total cells of CD 3+ T cells, CD 8+ cells, Tregs, in db/db mice group have significantly decreased compared to WT group: 4 079 ± 1 345 vs. 70 055 ± 3 374, 141.30 ± 28.36 vs. 2 714.00 ± 463.20, 148.00 ± 61.15 vs. 3 007.00 ± 639.90 ( P<0.01), while B cell has no change between two groups. Conclusions:By comparing the severity of anxiety-like behavior of db/db mice, the severity of white matter injury, and the number of T cells and B cells in brain tissue after dMCAO, immune-mediated brain white matter injury may aggravate db/db mice′s post-dMCAO anxiety-like behavior. Due to the gene dose effect, db/+ mice are not suitable as a control group for db/db mice in animal experiments involving anxiety-like behavior assessment.

Application of magnetic resonance quantitative score on the assessment of brain maturity in preterm infants with white matter injury / 中国新生儿科杂志

Objective:To study the relationship between white matter injury (WMI) and brain maturity in preterm infants at full-term corrected gestational age (cGA).Methods:A retrospective study was performed in preterm infants [GA≤32 weeks or birth weight (BW) ≤1 500 g] admitted to the neonatal intensive care unit of the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to August 2018 and the Northwest Women and Children's Hospital from January 2017 to June 2017. The infants received conventional magnetic resonance imaging (MRI) at cGA 37~42 weeks. The infants were assigned into the WMI group and the control group according to the WMI scoring system, including the total maturation scores (TMS) and four sub-item scores.Results:A total of 118 premature infants were enrolled in this study (17 cases in the WMI group and 101 cases in the control group). The GA was (30.3±1.7) weeks, and BW was (1 356±268) g. The proportion of delayed TMS in the WMI group was significantly higher than the control group [58.8%(10/17) vs. 31.7%(32/101), P<0.05]. The TMS of the WMI group were significantly lower than the control group [(10.7±1.8) vs. (11.8±1.5), P<0.05]. The sub-item scores of TMS showed that the myelination [(2.8±0.6) vs. (3.1±0.4), P<0.05] and glial cell migration bands of the WMI group [(1.6±0.4) vs. (2.1±0.6), P=0.004] were significantly lower than the control group and no significant differences existed in cortical folding and involution of germinal matrix tissue scores between the two groups. Conclusions:The brain maturity of preterm infants with WMI is substantially delayed than those without WMI, including delayed myelination and delayed disappearance of glial cell migration bands.

Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion / 神经科学通报·英文版

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.

Two kinds of stem cell nasal transplantation for treating white matter injury in premature rat infants / 中国组织工程研究

BACKGROUND: Stem cell transplantation has a significant neuroprotective effect on neurological diseases. Current transplantation methods such as arteriovenous transplantation and brain stereotactic transplantation are not suitable for clinical application in preterm infants. OBJECTIVE: To explore the feasibility of nasal transplantation of human umbilical cord mesenchymal stem cells and human neural stem cells for the treatment of white matter injury in premature rat infants. METHODS: Human umbilical cord mesenchymal stem cells were prepared from human umbilical cord tissue, and human neural stem cells were prepared from human embryonic brain tissue. In vitro migration of two kinds of cells was assessed by Transwell method. Forty 3-day-old Sprague-Dawley rats were randomly divided into sham operation group, model control group, human umbilical cord mesenchymal stem cell transplantation group and human neural stem cell transplantation group, with 10 rats in each group. Rats in all groups except the sham operation group were treated with right common carotid artery ligation and hypoxia for 90 minutes to establish a rat model of white matter injury in the preterm infant. Totally 1×106 cells were delivered intranasally in the transplantation group at 3 days after injury. Each nostril was infused with 5×105, and each nostril was infused once. On day 7 after injury, MBP immunofluorescence staining was used to detect the expression of myelin basic protein in the white matter of the brain to identify the damage of the white matter injury model. At 24 hours after transplantation, human umbilical cord mesenchymal stem cell migration was detected by anti-HuNu immunohistochemical method and human neural stem cell migration was detected by CM-Dil fluorescent labeling method. RESULTS AND CONCLUSION: (1) On day 7 after modeling, compared with the normal side, the positive area of MBP decreased in cingulate band, corpus callosum and external capsule of the affected side in the model of brain white matter injury in preterm infants (P < 0.05), indicating a successful modeling. (2) In vitro experiments showed that the migration rate of human neural stem cells was the same as that of human umbilical cord mesenchymal stem cells. (3) At 24 hours after the nasal transplantation, human umbilical cord mesenchymal stem cells migrated to the cortex, corpus callosum and hippocampus on the normal side and the damaged side, and human neural stem cells migrated to the damaged cortex, corpus callosum and hippocampus, and human umbilical cord mesenchymal stem cells migrated more than human neural stem cells. (4) Overall, these findings indicate that 24 hours after the nasal transplantation, human umbilical cord mesenchymal stem cells could survive and migrate to the normal side and the injury side, and human neural stem cells could survive and migrate to the injury side; and the migration of human umbilical cord mesenchymal stem cells was more extensive than that of human neural stem cells.

Loss of monocarboxylate transporter 1 aggravates white matter injury after experimental subarachnoid hemorrhage in rats / 医学前沿

Monocarboxylic acid transporter 1 (MCT1) maintains axonal function by transferring lactic acid from oligodendrocytes to axons. Subarachnoid hemorrhage (SAH) induces white matter injury, but the involvement of MCT1 is unclear. In this study, the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH. At 48 h after SAH, oligodendrocyte MCT1 was significantly reduced, and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function. Motor training after SAH significantly increased the number of ITPR2

Advance in MRI assessment of white matter injury and brain development in premature infants / 国际儿科学杂志

Premature white matter injury (WMI) is the immature white matter injury caused by ischemia,hypoxia and inflammation,which will affect normal neurodevelopment process and cause poor neurological outcomes.MRI has been widely used in early diagnosis of WMI because it can reflect the anatomical and pathological changes of WMI in premature infants.Functional MRI,such as diffusion-tensor imaging and magnetic resonance spectroscopy,can help quantitative assessment of the severity of WMI and neurodevelopment process so as to predict its neurodevelopment prognosis.This review summarizes the progresses in the application of MRI in the quantitative assessment of WMI and brain development in preture infants and its neurological outcomes.

Delayed Extensive White Matter Injury Caused by a Subdural Hemorrhage and Role of Corticospinal Tract Integrity

A subdural hemorrhage (SDH) is a common disorder with usually good prognosis. Most SDHs resolve with or without with minimal sequelae. We present a case report of a patient with SDH, who had delayed extensive white matter injury with disruptions of corticospinal tracts (CSTs) by diffusion tensor imaging (DTI) and showed abysmal prognosis, despite long-term rehabilitation. A 62-year-old man with an SDH underwent burr hole trephination for hematoma removal. Within 7 days, the hemorrhage diminished. At 12 weeks after the onset, the patient's weakness did not improve, and a follow-up magnetic resonance imaging revealed extensive leukomalacia, especially in the white matter. The DTI for CST revealed severe injury of CST integrity. He did not re-gain muscle strength and functional independence, despite 3 months of inpatient rehabilitation. This case describes SDH with delayed extensive white matter injury and exceptional poor prognosis and urges caution in that the SDH may induce very variable functional recovery. Besides, DTI for CST would be useful in predicting the long-term functional prognosis in extensive white matter injury.

Safety and early curative efficacy of lipocyte bioactive secretion in preventing white matter injury of premature infants / 中华实用儿科临床杂志

Objective To explore the safety and efficacy of intrathecal administration of adipose stem cells de-rived from bioactive secretome (ASCBS)in treatment of whiter matter injury (WMI)in the preterm infants. Methods Sixty - three cases of WMI were recruited according to the uniform standards from multiple medical centers and they were divided into 3 gestational age (GA)subgroups,which were 21 cases in group A (GA 24 - 28 + 6 ),20 cases in group B (GA 29 - 32 + 6 ),and 22 cases in group C (GA 33 - 36 + 6 ). The patients were randomly divided into treatment groups and control groups by tossing coins. The treatment groups received lumbar puncture followed with ASCBS intra-thecal injection once daily for 3 consecutive days. Follow - up study included Neonatal Behavioral Neurological Assess-ment (NBNA)at term - equivalent age and neurodevelopment at corrected age of 6 - month. Neurodevelopment was assessed by using the Bayley Scales of Infant Development and Peabody Developmental Motor Scale. The survival rates, NBNA scores,mental development index (MDI),psychomotor develop index (PDI),total motor development quotient, gross motor development quotient and fine motor development among each subgroup were compared. Results Sixty -three cases were recruited,including 31 in the treatment group and 32 in the control group. Only 1 case in the treatment groups lost in the follow - up. No clinical side effects were found in the treatment groups. There was no significant diffe-rence in the survival rate and complication in the preterms in all subgroups of the treatment group and control group (all P > 0. 05). The gross and total motor development quotient in the treatment group A was higher than that in the control group A(gross motor development quotient:98. 330 ± 6. 282 in treatment group A,90. 330 ± 3. 777 in control group A, P = 0. 040;total motor development quotient:97. 330 ± 4. 803 in treatment group A,91. 000 ± 4. 472 in control group A,P = 0. 023). The rest findings showed no significant difference between groups. Conclusion The treatment of WMI in preterm infants with ASCBS is safe and can promote the motor development of preterm infants with GA in 24 - 28 weeks.

Therapeutic effects on cerebral white matter injury of premature infants treated with acupuncture for promoting the governor vessel and tranquilizing the mind / 中国针灸

<p><b>OBJECTIVE</b>To explore the repair effects of acupuncture for promoting the governor vessel and tranquilizing the mind (acupuncture technique) on cerebral white matter injury of premature infants.</p><p><b>METHODS</b>A total of 56 cases of cerebral whiter matter injury of premature infants, the fetal age less than 35 weeks were selected and randomized into an observation group (27 cases) and a control group (29 cases). The routine basic rehabilitation therapy was used in the two groups. Additionally, in the observation group, the acupuncture technique was added, once a day and the treatment for 15 days was as 1 course. Totally, 3 courses of treatment were required. Before and after treatment, the cranial magnetic resonance imaging (MRI) and the diffusion tensor imaging (DTI) were adopted to observe the location and severity of cerebral white matter injury. The Gesell developmental scale was used to assess the nerve motor development.</p><p><b>RESULTS</b>After treatment, the difference was not significant statistically in the severity of cerebral white matter injury in the infants between the two groups (>0.05). The FA value of cerebral white matter in the interesting zone was increased as compared with that before treatment in the infants of the two groups (both<0.05). The result in the observation group was higher than that in the control groups (<0.05). After treatment, DQ value of each function zone in Gesell scale was all increased as compared with that before treatment in the two groups (all<0.05). After treatment, the DQ values of gross motor, fine motor and social adaptability in the observation group were higher than those in the control group (all<0.05). After treatment, the difference was not significant in DQ value of individual-social and speech behaviors between the two groups (both>0.05).</p><p><b>CONCLUSION</b>Acupuncture technique for promoting the governor vessel and tranquilizing the mind promotes the repair of the function in the premature infants with cerebral white matter injury and further benefits the promotion of the intelligence.</p>

The expression of bone morphogenetic protein 4 and its effects in ischemia-anoxemia induced white matter injury model / 中国小儿急救医学

Objective To investigate the ultrastructural alteration in brain tissues as well as the expression of bone morphogenetic protein(BMP) 4 and its effects on regulating myelination in the process of white matter injury development.Methods A total of 152 Sprague-Dawley newborn rats(3 days old) were randomly divided into white matter injury group(n=76) or control group(n=76).The white matter injury model was established by ligation of the right common carotid artery and hypoxic exposure(8% O2 and 92%N2),and samples were collected at 3d,7d,14d and 21d after operation.Morphological changes of the brain tissues were observed under a light microscope,while myelination was analyzed using a transmission electron microscope.The expression and location of BMP4 and myelin basic protein(MBP),a marker for myelination,was detected by immunohistochemistry staining,expression levels of BMP4 and MBP proteins were analyzed by Western blotting,and BMP4 mRNA expression was measured by real-time PCR.Results Observed under the light microscope,the cellular structure was clear,fibers arranged closely and orderly in the white matter of the control group.Whereas in the white matter injury group,sparse cells,loose mesh shaped white matter,and disorderly oriented fibers were observed.In the control group,myelin sheath had regular morphology,uniform density,and same thickness,observed using the transmission electron microscope.While in the white matter injury group,the myelin sheath was loosened,thinned,lamellar separated,and boundary obscured.Using immunohistochemistry staining,Western blot,and real-time PCR analyses,it was found that the protein and mRNA expression of BMP4 had no significant change with the increase of age in the control group,while it was rapidly increased with the extending of ischemic time in the white matter injury group.Comparing with the control group,the expression of BMP4 was significantly increased since 3d after operation in the white matter injury group(P<0.05),and the difference between two groups became more significant with the extending of ischemic time.The expression of MBP protein was analyzed by immunohistochemistry staining and Western blot,and a gradual increase was found in both groups with the increase of age.However,the expression of MBP protein was significantly decreased on 14d and 21d after operation in the white matter injury group compared with the control group(P<0.05).Conclusion Myelination disorders exists in white matter injury induced by ischemia-anoxemia.Meanwhile,the expression of BMP4 is significantly increased in the white matter injury group,indicating a possibility that BMP4 involves in the regulation of myelination disorders in white matter injury.

Clinical analysis of the early extrapulmonary complications in preterm infants with bronchopulmonary dysplasia / 中国小儿急救医学

Objective To clinically analyze the incidence of early extrapulmonary complications in premature infants with bronchopulmonary dysplasia(BPD),including periventricular intraventricular hemorrhage(PVH-IVH),white matter injury(WMI),parenteral nutrition associated cholestasis(PNAC) and metabolic bone disease(MBD),in order to direct the prevention and monitoring of these complications in BPD patients.Methods The clinical data of premature infants who were admitted to the neonatal department between September 2014 and December 2015 was retrospectively analyzed.A total of 87 premature infants diagnosed with BPD were studied as BPD group,while other 90 premature infants without BPD who were hospitalized at the same time were randomly selected as non BPD group.The occurrence of several common extrapulmonary complications was compared between two groups,including PVH-IVH,WMI,PNAC and MBD.Results The incidence of PVH-IVH in BPD group increased compared with non BPD group[(26.4%(23/87) vs 11.1%(10/90)] (P＜0.01),grade Ⅰ-Ⅱ PVH-IVH was more often seen in the BPD group too[24.1%(21/87) vs.11.1%(10/90)](P＜0.05),although the difference between two groups regarding the incidence of grade Ⅲ-Ⅳ PVH-IVH was not significant (P＞0.05).The incidence of WMI in BPD group was much higher than that in non BPD group[33.3%(29/87) vs 16.7%(15/90)] (P＜0.05),especially periventricular leukomalacia,the severe type of WMI,was more often found in BPD group than that in non BPD group[13.7%(12/87) vs 2.2%(2/90)](P＜0.05).The incidences of PNAC[22.9%(20/87) vs 5.5%(5/90)],MBD[17.2%(15/87) vs 3.3%(3/90)] and MBD with imaging changes[6.9%(6/87) vs 0] were all higher in BPD group compared with non BPD group,with significant differences between the two groups (P＜0.05).Conclusion BPD patients are more likely to have early extrapulmonary complications like PVH-IVH,WMI,PNAC and MBD than other preterm infants.It is crucial to prevent these complications reasonably and monitor them regularly for the BPD patients in order to improve the quality of life.

Novel intervention target for white matter injury-neurovascular unit / 国际儿科学杂志

Perinatal cerebral white matter injury is the most common form of brain injury in premature infants which can lead to developmental disorders of the neurological system,even long-term neurological sequala.The pathogenesis of white matter injury is complicated,and until now there is no effective intervention option.In recent years,as the structural and functional integer of the nervous system,neurovascular unit has attracted much attention in the neuroscience field.The constituents of neurovascular unit and their interaction in the white matter,as well as the progress in the pathophysiology,prevention and treatment of white matter injury are reviewed in this paper.

Neuroprotective effect of paracrine extracts derived from human adipose stem cells on white matter injury of neonatal rats / 中国新生儿科杂志

Objective To explore the effect of paracrine extracts derived from human adipose stem cells on white matter injury of neonatal rats and to compare the difference of therapeutive effect between the cerebellum medulla oblongata pool injection and the jugular vein injection.Method A total of 73 three-day-old SD rats were chosen to establish the model of white mater injury.After 24 hours,the 73 rats were randomized into the experimental group (n =46) and the control group (n =27).Then the experimental group was reclassified into ventricular group (n =23) and intravenous group (n =23).In the ventricular group,the paracrine extracts of human adipose stem cells was injected locally into the cerebellum medulla oblongata pool injection,while the extracts was injected into the jugular vein in the intravenous group.The control group was reclassified ventricular control group (n =15) and intravenous control group (n =12),and equivoluminal saline was injected the same way as the experimental group.Frozen sections of the brain tissue from 3 rats of each experimental group one day after injection were stained with fluorescein-conjugated streptavidin to study the distribution of the extracts.The brain tissue of 3 rats from each subgroup 3 days after injection were stained with hematoxylin eosin (HE) to observe the pathomorphological changes.While 7 days later,myelin basic protein (MBP) of white matter which was obtained from 7 rats of each group was detected by immunofluorescence staining.28 days after injection,the remaining rats were assessed by neurobehavior tests.For the rats that died during the experiment,the same number of the rats would be substituted in this study.Result The paracrine extracts were found to transfer to the brain lesion area,and the amount of the extracts was more in the ventricular group.The results of the HE staining showed that the white matter injury was more severe in the ventricular control group,and extensive area of infarction were found in this group.White matter injury was mild in the experimental group,and the structure of the corpus callosum was more complete in the ventricular group.MBP semi-quantitative scores of the ventricular group (0.7 ± 0.3) and intravenous group (1.7 ± 0.3) were lower than those of ventricular control group (3.4 ± 0.4)and intravenous control group(3.3 ±0.3).And the MBP scores of ventricular group was significantly lower than that of intravenous group (P ＜ 0.05).The scores of the neurobehavioral tests of the experimental group were significantly higher than those of the control group,while the scores of the ventricular group were significantly higher than those of the intravenous group (P ＜ 0.05).Conclusion The paracrine extracts derived from adipose stem cells could improve the prognosis of white matter injury,and cerebellum medulla oblongata pool injection showed better curative effect than the jugular vein injection.

Research progress of white matter injury following congenital heart disease / 国际儿科学杂志

Congenital heart disease is the most common birth defect.With the significant improvements of cardiac surgical techniques,the survival of newborns and infants with complex congenital heart disease(CHD) has obviously been increased.However,neurological sequelae are still common and up to 25 ％ ～50％.The most important lesion after CHD surgery is white matter(WM) injury.Recent studies show that periventricular leukomalacia disease characterized by WM injury is common in C-HD infants especially after cardiac surgery.It is previously thought to be due to the cardiopulmonary bypass and surgical operation.However,with the advances in surgery and medical diagnostic technology and development of basic research in recent years,it is discovered that WM injury in infants with CHD is a complex lesion influenced by preoperative,operating and postoperative factors.The movement disorders and the defects of attention,learning and other aspects in the late growth of these children bring a huge economic burden to the family and society,reducing the quality of the population.Therefore,exploring etiology,mechanisms and control methods of WM injury in infants with CHD becomes a hot topic in recent years,and it may also become an important direction for future research,aiming to the significant improvements in CHD children with neurodevelopmental damages.

Protective effects of activated protein C on neurovascular unit in a rat model of intrauterine infection-induced neonatal white matter injury / 华中科技大学学报（医学）（英德文版）

Activated protein C (APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 μg/kg lipopolysaccharide (LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection- induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin (H&E). Immunohistochemistry was used to evaluate myelin basic protein (MBP) expression in the periventricular white matter region. Blood-brain barrier (BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 (PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection- induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.

The epidemiological study of the incidence in encephalopathy of prematurity / 中华实用儿科临床杂志

With the neonatal intensive care techniques developing,the survival rate of preterm infants has increased markedly.However,these survival preterm infants are extremely vulnerable to develop various diseases,of which brain injury is the most important cause of the disability in preterm infants.At present,encephalopathy of prematurity,the incidence of which is rarely reported in domestic and national reports,mainly refers to white matter injury (WMI).This article reviews the different domestic and national reports about the incidence of encephalopathy of prematurity.

Diagnosis and evaluation on the MRI findings in the premature infants with white matter injury / 临床儿科杂志

Despite that improved neonatal intensive care unit therapies have reduced the mortality of preterm neonates, neo-natal neurodevelopmental morbidity persists at high rates. There is increasing recognition that following perinatal brain injury, cognitive deifcits in preterm neonates can often occur in the absence of signiifcant impairment and cerebral palsy often due to non-severe white matter injury (WMI). Minicystic and diffusive white matter lesions that need MRI detecting make up the predominant role in the preterm brain injury. The target cells and tissue of WMI in the preterm infant not only focus to preoligodendrocytes and white matter, but also involve neurons and grey matter. In fact, brain developmental trajectory in the premature infant with WMI is a mixed disorder of destructive and dysmature processes. Current MRI applied with high resolution could detect the punctate and diffusive WMI at early stage, distinguish the hemorrhagic lesions from reactive gliosis, analyze cerebral metabolism, and even describe the developmental progresses of myelination, ifber tract, cortex and cerebral connectome. But the predictive value of dif-ferent MRI techniques in brain development requires more and long-term research through the all life stages.