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Objective:To study the protective effects and mechanisms of melatonin (MTn) on lipopolysaccharide (LPS) and hypoxic-ischemic(HI) induced white matter damage (WMD) in neonatal rats.Methods:Seventy-two 3-day-old newborn Sprague-Dawley (SD) rats were randomly assigned into sham operation group (the sham group), model group (the HI group) and MTn intervention group (the HI+MTn group) ( n=24 for each group). For the sham group, only dissection of the right common carotid artery was performed without ligation. Animal models of WMD were established using LPS pretreatment and HI method in both the HI group and HI+MTn group. The HI+MTn group received MTn intraperitoneal injection (15 mg/kg, 1 h before LPS injection and then once daily). The HI group and the sham group received equal volume of normal saline containing 1% ethanol intraperitoneal injection. The rats were sacrificed on d7 of experiment and periventricular white matter (PVWM) was collected for hematoxylin-eosin (HE) and TUNEL staining to determine WMD and apoptosis. The distribution and morphology of microglial cells in the PVWM were studied using IBA1 immunofluorescence staining. Reactive oxygen species (ROS) kit was used to detect ROS. The expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, IL-18 and mitochondrial autophagy markers (pink1 and parkin) were determined using real-time quantitative PCR. Results:Compared with the sham group, the HI group showed WMD, cell degeneration and necrosis,increased cell apoptosis and increased expressions of NLRP3 inflammasomes and downstream inflammatory factors (IL-1β and IL-18) in PVWM. Compared with the HI group,the HI+MTn group showed reduced WMD, cell apoptosis, microglia infiltration and inflammatory factors expression. MTn increased pink1 and parkin expression and reduced ROS production in PVWM.Conclusions:MTn reduces ROS production by enhancing mitochondrial autophagy and inhibits NLRP3 inflammasomes hyperactivation to alleviate endotoxin- and HI-induced WMD in neonatal rats.
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At present， major depressive disorder （MDD） is highly prevalent with advanced neurological disorders as the main pathological manifestations. As the physiological function bearer of higher neural activity， gray matter has become the focus of MDD treatment. However， recent research has shown that white matter and gray matter are independent of each other in the central nervous system （CNS）， and their functions are integrated and linked. In addition to gray matter damage， white matter damage is also the core driving event of disease progression and determines the outcome of MDD. At the treatment level， the current drug treatment of MDD mainly focuses on gray matter repair， while ignoring the importance of white matter integrity for the treatment of the disease， which has become the weakness of the current treatment of MDD. Traditional Chinese medicine （TCM） has good application potential in white matter repair. This paper elaborated on the following three aspects. ① The roles of white matter damage in the occurrence and development of MDD were summarized. ② The key link of white matter repair in MDD was elaborated with microglia microenvironment regulation as the entry point. ③ The application value of TCM in white matter repair in MDD was analyzed. This review aims to highlight the importance of white matter integrity in the treatment of MDD and is expected to expand the understanding dimension of the activity of related Chinese medicines in MDD from the perspective of white matter repair and analyze its potential application value.
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Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.
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Objective To investigate the mechanism of white matter damage (WMD) and the neuroprotective effect of Xenon on neonates with WMD.Methods Three-day-old SD rat pups (n =96) were randomly divided into the blank control group (n =24),the WMD control group (n =24),the Xenon intervention group A (n =24) and the Xenon intervention group B (n =24) by random number method according to their birth time.WMD rat models were successfully established by giving intraperitoneal injection of lipopolysaccharide(LPS) 0.05 mg/kg combined with carotid artery ligation and hypoxia for 1 hour in the WMD control group and the Xenon intervention groups.In the control group,only 9 g/L saline (0.05 mg/kg) was injected intraperitoneally,while carotid artery ligation and hypoxia were not administered.Rats in Xenon intervention group A and group B were given inhalation of 500 mL/L Xenon for 3 hours at 0 and 2 hours respectively after establishment of the models.Six rats in each group were randomly selected and decapitated at 0,24,48 and 72 hours after the intervention.The brain white matter on the right was analyzed by using HE staining and myelin basic protein(MBP) immunofluorescence staining,and real-time quantitative polymerase chain reaction was used to detect the expressions level of CLIC4 mRNA.Results (1) Brain tissue pathology:compared with the blank control group,the brain white matter on the right of the WMD control group and the Xenon intervention group A and group B had loose and disordered structure,nuclear pyknosis and cytoplasm loosening.However,the lesions in both Xenon intervention group A and group B were significantly less than those in the WMD control group,and there was no significant difference between the Xenon intervention group A and group B.(2) MBP measurement:the number of MBP-positive cells in the brain white matter on the right of WMD control group was significantly lower than that in the blank control group,while compared with WMD control group,they were significantly higher in Xenon intervention group A and group B.(3) CLIC4 mRNA expression level:compared with blank control group,the expressions levels of CLIC4 mRNA at most time point were higher both in the WMD control group and the Xenon intervention group A and group B (all P ＜ 0.05),except the time point 24 h in the Xenon intervention group A.The expressions of CLIC4 mRNA in group A and group B were significantly decreased compared with those in the WMD control group (all P ＜ 0.05).However,there were no significant differences between Xenon intervention group A and group B (P ＞ 0.05).Conclusions The expressions of CLIC4 mRNA in brain tissues on neonatal rats with WMD significantly increased,indicating that the mitochondrial pathway could be one of the pathological processes of WMD.Early Xenon intervention may reduce neonatal WMD by reducing the expression of CLIC4 mRNA,which plays a neuroprotective role.
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Probiotics is important to promote the absorption of nutrients,to respond to immune response,to suppress inflammatory cytokines and so on.Premature infant white matter damage is the main pathological form of preterminfant brain injury,and it is often complicated with cognitive,hearing impairment,mental retardation,cerebral palsy,etc.The latest finding is that probiotics can ensure balanced nutrition intake,improve body immunity,inhibit inflammatory factor release,reduce nerve cell edema,enhance antioxidant enzyme activity and oxygen free radical scavenging,inhibit excitatory amino acid activity,reduce excitatory toxicity,and promote the recovery of function of nerve cells in white matter damage in premature infants through microbiota-gut-brain axis.This article reviews the protection and repair of probiotics in premature infants with white matter damage.
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Objective To explore the relationship of serum ubiquitin carboxy terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) with brain injury in preterm infants. Methods A total of 130 premature infants with gestational age <34 weeks from August 2014 to October 2016 were recruited. Blood samples were collected at 6 h and 72 h after birth. The levels of serum UCH-L1 and GFAP were detected by ELISA method. According to the results of cranial ultrasound and MRI examination, the premature infants were divided into white matter damage (WMD) group, periventricular intraventricular hemorrhage (PVH-IVH) group, and no brain injury group. The levels of serum UCH-L1 and GFAP in preterm infants between the three groups, mild to severe brain injury were compared. Results At 6 h and 72 h after birth, the levels of serum UCH-L1 and GFAP among no brain injury group, PVH-IVH group and WMD group were significantly different (all P <0.001). The level of serum UCH-L1 and GFAP were the highest in the WMD group and the lowest in no brain injury group at both 6 h and 72 h after birth. The levels of serum UCH-L1 at 72 h after birth were significantly lower than those at 6 h after birth in PVH-IVH group and WMD group, while the levels of serum GFAP at 72 h after birth were significantly higher than those at 6 h after birth in both of the two groups (all P<0.05). The levels of serum UCH-L1 and GFAP in severe PVH-IVH group and severe WMD group were significantly higher than those in the mild group at 6 h and 72 h after birth (all P<0.05). Conclusions The levels of serum UCH-L1 and GFAP in preterm infants can be used as sensitive markers for early evaluation of brain injury, which can help determine the severity of brain injury in preterm infants.
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Objective To investigate the pathogenesis of white matter damage (WMD) and the effects of xenon intervention on the expression of EphB4 and EphrinB2 mRNA in the brain tissue of neonatal rats.Method Three-day-old SD rat pups (n =96) were randomly assigned into sham group (n =24),model group (n =24),xenon intervention group 1 (n =24) and xenon intervention group 2 (n =24).The WMD model was established by injected of lipopolysaccharide (LPS) 0.05 mg/kg combined with ligation of the right carotid artery for 1 h in the last three groups.Rats in xenon intervention group 1 inhaled 50％ xenon immediately for 3 h after modeling,while rats in xenon intervention group 2 inhaled 50％ xenon for 3 h at 2 h after modeling.After the completion of xenon intervention,6 rat pups in each groups were sacrificed at 0 h,24 h,48 h and 72 h.The pathologic examination of periventricular tissue was conducted with hematoxylin-eosin staining (HE) and the expression of EphB4 and EphrinB2 mRNA was assayed by real-time quantitative polymerase chain reaction (RT-PCR).Statistical analysis was then performed.Result (1)The structure of white matter in model group became loose,band net-like,with significant nucleus pyknosis.The pathological damages in xenon intervention group 1 and 2 were lighter at 24 h,48 h and 72 h than model group,with less karyopycnosis.(2) Compared with the sham group,the expressions of EphB4 and EphrinB2 mRNA at 0 h,24 h,48 h and 72 h were significantly higher in the model group and xenon intervention group 1 and 2 (P ＜ 0.05),except for the EphB4 mRNA in xenon intervention group 1 at 72 h (P ＞ 0.05).The expressions of EphB4 and EphrinB2 mRNA at each time point in xenon intervention group 1 and 2 were decreased significantly than the model group (P ＜ 0.05),except for the EphB4 mRNA in xenon intervention group 2 at 72 h (P ＞ 0.05).However,there was no statistically significant difference on EphB4 and EphrinB2 mRNA between two xenon intervention groups at each time point (P ＞ 0.05).Conclusion The expression of EphB4 and EphrinB2 mRNA are appreciably increased in brain tissue of neonatal rats with WMD,which indicates the reactive angiogenesis.The intervention with xenon may play a neuroprotective role through reducing the expressions of EphB4/EphrinB2 mRNA and angiogenesis,and early intervention may be better.
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OBJECTIVE: To investigate the effect of γ-secretase inhibitor DAPT in inflammation-induced brain white matter injury in neonatal mice. METHODS: Sixty C57BL/10J neonatal mice are randomly divided into control group, control+DAPT (10 mg•kg-1) group, inflammation (LPS) group, LPS+DAPT group (inflammation exposure after 10 mg•kg-1 DAPT treatment). All neonatal mice were killed and brain was removed to the following observation and detection:at P5, the mRNA expression variation of IL-1β, IL-8,TNF-α,Hes1 and NICD by Real-time PCR methods. Oligodendrocytes were identified by immunofluorescence staining. Myelin basic protein (MBP) protein expression was detected by Western blot assay. RESULTS: LPS group showed brain injury characterized by inhibition of brain development. There were significant differences in mRNA expression of IL-1β, IL-8, TNF-α, Hes1 and NICD between LPS+DAPT group and LPS group (P<0.05), and the mRNA expression of IL-1β, IL-8,TNF-α,Hes1 and NICD in inflammation-treated were significantly increased than control group (P<0.05). The results showed more expression of MBP in LPS+DAPT group compared with LPS group (P<0.05). Compared with the blank control group, which was obviously decreased after 48 h of inflammation (P<0.05).CONCLUSION: Inflammation leads to abnormal of notch signal expression in neonatal mice, and which is shows inflammation involved in brain damage.Its mechanism is probably associated with the maturation of oligodendrocytes.
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Objective To explore the protective effect of miconazole on white matter damage (WMD) in neonatal rats. Methods Three-day-old neonatal SD rats were randomly divided into sham group, WMD model group, 10 mg/(kg·d) miconazole group and 40 mg/(kg·d) miconazole group with 15 rats each. Rats in WMD model group were subjected to the ligation of right carotid artery, and then kept in a chamber with 6% oxygen and 94% nitrogen for 80 min to establish the white matter damage model. The rats in miconazole group were intraperitoneally injected with different doses (10 and 40mg/kg) of miconazole, dissolved in dimethyl sulfoxide (DMSO), for five consecutive days, and rats in WMD model group were injected with the same volume of DMSO. Myelin basic protein (MBP) of white matter was detected by immunofluorescence staining and western blot. Myelin sheaths of corpus callosum were observed by transmission electron microscopy. Weight changes of rats were compared among groups. Results Immunofluorescence staining and western blot showed that, after treatment with miconazole, the MBP expression level of corpus callosum was higher than in WMD model group (P<0.05). In WMD model group, the myelin sheath of corpus callosum had loose structure and a large number of small vacuoles with decreased thickness of myelin sheath. After treatment with miconazole, myelinolysis induced by anoxia and ischemia could be improved significantly. The increase in weight of rats in WMD model group was significantly less than that in sham group. And after miconazole treatment, the rate of weight gain of rats was increased. Conclusion Miconazole can significantly reduce the brain white matter damage induced by anoxia and ischemia through promoting myelination, and then improves the growth and development in rats.
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Cerebral white matter damage is the most common form of brain injury in premature infants,which is the main cause of neurological and mental injury and cerebral palsy.Imaging examination plays an important role in the diagnosis and follow-up of white matter damage.Because of the safe and accurate characteristics,nuclear magnetic resonance has become the most common imagine form.Different from the traditional nuclear magnetic resonance technique,diffusion tensor imaging (DTI) can get quantitative analysis of cerebral white matter fiber bundle in vivo.This technology has become a powerful tool for the evaluation of white matter damage.The article summarizes the application of DTI in the neurodevelopmental evaluation of cerebral white matter damage in premature infants.
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Objective:To explore the effect of infection on autophagy-related proteins,Beclin-1 and LC3,expression in cerebral white matter in newborn rats.Methods: A total of 64 two-day-old Sprague-Dawley(SD) rats were randomly divided into control and experimental groups(n=32 each).At day 2 to 6 after birth,the rats in experimental group were intraperitoneally injected with 0.6 mg/kg of lipopolysaccharide(LPS) once a day to establish a white matter injury induced by infection in neonatal rats while the rats in control group were injected with equal amounts of normal saline.Rats were sacrificed to collect brain tissues at 12 hour,1,3,5 d after model establishment.HE staining was performed to observe the pathological changes.Changes in the expression of Beclin-1 and LC3 in rat white matter were examined by Western blot and RT-PCR.Results: Growth and development of rat in experimental group was slow,cerebral white matter lesions were obvious.Compared with the control group,the experimental group Beclin1 and LC3 protein and mRNA levels in the model after 12 h began to express,1 d reached the peak,and then decreased,each time points were higher than the control group(P<0.05).Conclusion: Early infection in neonatal rats can cause white matter damage;the expression of autophagy-related proteins,Beclin1 and LC3,showed that autophagy may be involved in the pathological process of white matter damage induced by infection.
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Objective To identify high?risk factors of white matter damage ( WMD ) in premature infants,in order to reduce the incidence and improve the prognosis of brain injury?Methods Five hundred and seventy?seven cases of preterm infants treated from January 2012 to December 2013 in the Pediatrics Department of Affiliated Hospital of Qingdao University were slecteted?According to MRI of the brain at 2 weeks after birth, all the patients were divided into WMD group(133 cases) and the control group(444 cases)?Single?factor and multifactor logistic regression were used for the analyses of the high?risk factors of WMD?Results WMD incidence was 23?05%( 133/577) in 577 cases of premature infants,with 108 cases( 81?2%) of focal injury,5 cases(3?8%) of diffuse injury and 20 cases(15?0%) of periventricular leukomalacia(PVL) injury?There was significant statistically difference in different gestational age( P=0?017)?Multi factor Logistic regression analysis showed that metabolic acidosis(OR=4?489,P=0?000),asphyxia(OR=3?519,P=0?000),perinatal infection ( OR=2?650,P=0?003) were independent risk factors for WMD,while cesarean( OR=0?293,P=0?000) was protective factor for WMD?Conclusion WMD is a complex interaction outcome of multiple risk factors in premature infant?Perinatal hypoxia and infection are the main risk factors of WMD in premature infants.
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Objective To evaluate whether recombinant human erythropoietin (rh-EPO) could increase the angiogenic responses in preterm rat models with periventricular white matter damage (PWMD).Methods Three-day postnatal rats were divided into 3 groups randomly:the sham group,the hypoxic-ischemic (HI) group and the recombinant human erythropoietin(rh-EPO)treatment group.Rat pups underwent permanent ligation of the right common carotid artery followed by 60 mL/L O2 for 4 h or sham operation and normoxic exposure.Immediately after the HI,rats received a single intraperitoneal injection of rh-EPO (5 U/g)or saline.Angiogenesis-related cells (CD34 + cells),microvessel density (MVD)and arteriovenous related genes (ephrinB2 and EphB4)were examined at 48 h and 96 h after operation.Results At 48 h after operation,the proteins of CD34 in HI rats increased compared with the sham rats (HI group vs Sham group:0.54 ± 0.05 vs 0.42 ± 0.05,P ＜ 0.05).However,the MVD,the mRNA of ephrinB2 and EphB4 did not change (P ＞ 0.05).The proteins of CD34,the mRNA of ephrinB2 and EphB4 increased after rh-EPO treatment compared with HI rats.However,the MVD did not increase.As the proteins of CD34 increased further at 96 h after operation (HI group vs Sham group:0.85 ± 0.06 vs 0.62 ± 0.06,P ＜ 0.05),the MVD (3.14 ± 1.21 vs 1.50 ± 1.04),ephrinB2 (7.51 ± 1.89 vs 1.28 ± 0.24) and EphB4 (4.58 ± 0.82 vs 1.21 ± 0.22) also increased (all P ＜ 0.05).And the proteins of CD34 increased after administration of rh-EPO(EPO group vs HI group:0.98 ± 0.07 vs 0.85 ± 0.06,P ＜0.05) and MVD(EPO group vs HI group:4.71 ± 1.38 vs 3.14 ± 1.21,P ＜0.05) were increased after administration of rh-EPO.However,the ephrinB2 and EphB4 did not increased after administration of rh-EPO at 96h time point.Conclusion Endogenous regenerative response is triggered in the damaged tissues and rh-EPO increases the angiogenesis in model rats with PWMD.
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Objective To investigate the protective effect of melatonin and its possible mechanism for repairing in the immature white matter damage due to brain hypoxia-ischemia (HI).Methods Forty-eight three-day SD rats after birth were randomly divided into 3 groups:sham-operated(SHAM) group,HI group and melatonin treatment(MT) group.Periventricular white matter damage (PWMD) to animal models were estabished according to Rice modeling.MT group was treated with melatonin pre-operatively,immediately postoperation,1 hour postoperation and 24 hours postoperation via intraperitoneal injection,and the other groups were injected with the same volume of dissolvent.The rats were executed by decollation after 2 days and 14 days.The histological changes in periventricular white matter were observed by HE staining and immunohistochemistry.Results For the 3 groups,the structure in ope-ration side of the white matter in the peripheral ventricles of the brain 2 days postoperation were significant different (P ＜0.05).The O4 positive cells decreased one by one/greatest in the SHAM group[(75.548 ± 7.333)/hpf] followed by MT group [(59.971 ± 3.635)/hpf],and HI group [(40.511 ± 2.848)/hpf] (P ＜ 0.05).The expression of Casepase-3 increased in the SHAM group (107.724 ± 10.266),MT group (132.289 ± 8.537),and HI group (202.168 ± 14.367),and the difference was statically significant (P ＜ 0.05).Ventricular index was greater in operation side of the white matter in the peripheral ventricles of the 14-day-brain in the SHAM group(0.928 ±0.063),MT group (1.813 ± 0.110),HI group (2.752 ± 0.201),increasingly,while absorbance value of myelin basic protein decreased one by one in sequence(39.504 ± 1.673,21.729 ± 1.614,11.344 ± 1.118).Conclusions MT plays a role in protecting the periventricular white matter via inhibiting the apoptosis of oligodendrocyte progenitor cell,and thus benefits the PWMD.
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76 premature babies stayed in NICU of Taian City Central Hospital from January, 2012 to December, 2012 whose gestational age is from 31 week to 35 week. The babies were scanned with MRI, DTI and MRS. According to the statistics of Brain White Matter Damage Based on MRI those babies are divided into case group and control group which has 38 babies respectively. 38 full-term infants, who don’t have history of perinatal asphyxia, whose MRI is normal, are taken as control group. The ADC value and FA value in different ROIs and different metabolite peak ratios in two groups are tested with DTI and MRS respectively.Results: 1.With the growth of gestational age the ADC value decreases while the FA value increase gradually. 2.With the deterioration of white matter damage the values of Cho, Lac, Cho/Cr, Cho/NAA rise while the values of NAA, NAA/Cho, NAA/Cr fall.Conclusion: Cerebral white matter damage can severely influence the changes of brain inner water molecular diffusion and anisotropy and metabolin. By uniting the DTI and MRS these two technologies together, people can diagnose cerebral white matter damage and white matter damage in the early period.
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Objective Cell therapy is a possible effective way to treat myelination disorder diseases.Cell therapy needs to apply a method for culturing oligodendrocyte precursor cells.Therefore,this study was to develop a stable,efficient and economical method for obtaining human oligodendrocyte precursor cells (OPCs) in order to provide cell required for clinical treatment.And this will provide a new option for clinical applications.Methods Human OPCs were obtained through magnetic bead sorting and cultured in OPCs proliferation medium.For a short-time (2,4,6,8days) and long-time culture,morphology of OPCs was observed.The fourth generation of OPCs was analyzed for expression of OPCs specific markers O4,Soxl0 and platelet derived growth factor alpla receptors(PDGFαR) and the capacity to differentiate into oligodendrocytes by immunofluorescence staining.At the same time,the effects of B27 and N1 on OPCs growth state were inspected as well.Results For a short-time culture,OPCs had typical bipolar or tripolar morphology and proliferated in good condition.For a long-time culture,all 4 generations OPCs had typical bipolar or tripolar morphology;the fourth generation OPCs highly(＞ 90％) expressed 04,Sox10 and PDGFαR,after induction,OPCs could be differentiated into oligodendrocytes.After 4 generations of long-time culture,OPCs already maintained the original sharp,high purity and had the capacity to differentiate into oligodendrocytes.It was indicated that this culture system was suitable for human OPCs for a long-time culture.Conclusions Overall,using this culture system,isolated human OPCs not only can be stably cultured and proliferated in vitro,but also have the capacity to differentiate into oligodendrocytes.From this reproducible method,a large number of human OPCs can be stably obtained in vitro as convenient as possible.And this will provide a new option for clinical applications.This method uses fewer cytokines.Therefore,this method will provide stable,efficient and economical OPCs for cell therapy of myelination disorders or myelin damage diseases.
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White matter damage in premature infant is the main form of brain damage in low birth and very low birth weight children,but its etiology and pathogenesis is not fully clear.Present studies show that Tolllike receptors(TLR) play an important role in the white matter damage mechanism.TLRs are regulators of innate immune responses.The studies have found that TLRs signaling pathway is activated to secrete large amounts of TNF-α,IL-1β,reactive oxygen species (ROS) and reactive nitrogen (RNS),NO,and other inflammatory factors,inducing the immune response.Nerve immune response damages brain white matter,namely the activation of microglia and proliferation of astrocytes in brain.TLRs provide a new research direction for prevention and treatment.Therefore,the research and progress of toll-like receptors in premature brain white matter injury disease are
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Objective To explore the IL-8 and ICAM-1 in premature infants with cerebral white matter damage (CWMD) and their correlations with prognosis. Methods One hundred and two cases of CWMD were selected from March 2009 to June 2012 as experimental group and 42 cases of normal preterm children were selected as control group. Serum IL-8 and ICAM-1 levels were measured during 48-72 h after birth. Motor development index (psychomotor developmental index, PDI) and mental development index (mental development index, MDI) were evaluated by Bayley scale. The correlations of IL-8 and ICAM-1 levels with prognosis were analyzed. Results Serum IL-8 and ICAM-1 levels in the experimental group were signiifcantly higher than those in the control group (P<0.05). MDI and PDI scores in the experimental group were signiifcantly lower than those in the control group (P<0.05). There were negative correlations of serum IL-8 and ICAM-1 levels with MDI (r=-0.64, P<0.05;r=-0.66, P<0.05)+and PDI (r=-0.70, P<0.05;r=-0.71, P<0.05). Conclusions Serum IL-8 and ICAM-1 levels in infants with CWMD are signiifcantly increased, and are negatively correlated with MDI and PDI scores.
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Objective To investigate the early MRI performance and the evolution of premature infants who developed into periventficular leucomalacia (PVL) eventually.Methods Twelve premature infants diagnosed as PVL by MRI in the department of neonatology in Shengjing Hospital of China Medical University from Jan 2010 to Dec 2013 were selected,all of the cases underwent conventional MRI and diffusion-weighted imaging (DWI) examination twice,the first examinations were finished in 2 to 7 days (mean 5.5 d) after birth and the second examinations were taken in 17 to 23 days(mean 20.3 d).Results The first examination showed:all cases performed high signal intensity of periventricular matter,including 6 diffuse and symmetrical,3 linear and 3 clustered high signal.However,only 5 of the 12 cases showed slightly high signal on T1 weighted image with low signal on T2 weighted image on conventional MRI,the other 7 cases showed no change;for the reexamination:foci of different numbers and sizes showed up in all cases,with the performance of low signal on T1 weighted image,high signal on T2 weighted image and low signal on DWI correspondingly.Conclusion DWI is superior to conventional MRI in finding and forecasting PVL;diffuse white matter damage have more probability to develop into PVL,severe local white matter damage such as multi-clustered and linear damage also can develop into PVL.
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Objective To monitor the function of infection on myelination in white matter damage,neonatal Wistar rats of postnatal day 2 (P2) and postnatal day 7 (P7) were injected intraperitoneally with the same doses of lipopolysaccharides (LPS),and 2',3 '-cyclic nucleotide phosphodiesterase (CNPase) and myelin basic protein (MBP) were labeled in immature oligodendrocytes and mature oligodendrocytes.To investigate the function of tumor necrosis factor(TNF)-α according to test the change of TNF-α expression in the brain.Methods Ninty-six neonatal Wistar rats were randomly divided into four groups (each group 24 rats):group A:LPS (5.0 mg/kg) was injected intraperitoneally on P2 ; group B:LPS (5.0 mg/kg) was injected intraperitoneally on P7 ;group C1 and C2 were control groups in which equal amount of normal saline was injected intraperitoneally on P2 or P7.The expression of CNPase at 24 h after injection and MBP at P14 in brain tissue of each group were measured by immunohistochemistry and express of TNF-α mRNA at 4 h after the injection was measured by RT-PCR.Results Punctate hemorrhage in the corpus callosum,external capsule and intraventricular hemorrhage were seen in group A.Periventricular leukomalacia appeared in the corpus callosum and glial cells hyperplasia could be seen periventricular in P14 rat brains,but not found in the group B and any of the saline-injected rat brains.Compared with group C1 and C2 respectively,CNPase-positive cells showed obvious decrease in the area of white matter in periventricular in group A(106.93 ± 2.62 vs 113.67 ± 2.69,P ＜ 0.01) and group B (96.37 ± 1.82 vs 101.65 ± 2.01,P ＜ 0.01).Following LPS treatment in group A,the protein expression of MBP in neonatal brain decreased evidently compared with group C1 at P14 (128.21 ± 2.99 v s 134.81 ± 2.98,P ＜ 0.01),while no significant change was found between group B and group C2(134.77 ±3.68 vs 134.81 ±2.98,P ＞0.05).After 4h of the LPS treatment,the level of TNF-α mRNA was greatly increased in group A,it was significantly higher than that in group B (1.79 ± 0.04 vs 1.18 ± 0.04,P ＜ 0.01).Conclusion Intraperitoneal injection of LPS to the development neonatal rats can lead to dysmyelination and white matter damage.The expression of TNF-oα mRNA increased significantly in these immature neonatal rats,while only myelination delay occurred in those of mature neonatal rats without dysmyelination.