Periventricular leukomalacia （PVL）, a white matter injury （WMI） affecting the premature infant＇s brain is commonly associated with ce- rebral palsy （CP）. Among premature infants 〈 1,500 g, approximately 7,000 ...Periventricular leukomalacia （PVL）, a white matter injury （WMI） affecting the premature infant＇s brain is commonly associated with ce- rebral palsy （CP）. Among premature infants 〈 1,500 g, approximately 7,000 develop CP yearly and 20,000-30,000 exhibit major cognitive deficits yearly （Volpe, 2009）. PVL results from hypoxia-ischemia （HI） with or without infection and is characterized by white matter necrotic lesions, hypomyelination, microglial activation, astrogliosis, and neuronal death. Risk factors for the development of PVL include： prematurity associated with immature cerebrovascular development, HI insults with lack of appropriate auto-regulation of cerebral blood flow, free radical production, energy deprivation, intrauterine infec- tion and chorioamnionitis. Affected infants show definitive signs of cerebral palsy such as spastic diplegia, seizures, developmental delay, visual and hearing impairment, scoliosis and incontinence by 6-9 months of age. PVL can also occur in term infants with certain con- genital cyanotic heart disease which will not be our focus here （Volpe, 2001）.展开更多
Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time （Bowen and Atwood, 2004; Grady, 2012）. Aging-related...Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time （Bowen and Atwood, 2004; Grady, 2012）. Aging-related changes are typically accompanied by decline in cognitive function, urinary control, sensory-motor function, and gait ability （Bradley et al., 1991; Bowen and Atwood, 2004; Hedden and Gabrieli, 2004; Grady, 2012; Moran et al., 2012）. In addition, a number of studies have suggested changes in brain structure with normal aging, such as decrease in cortical thickness or increase in ventricular width （Blatter et al., 1995; Tang et al., 1997; Uylings and de Brabander, 2002; Preul et al., 2006; Apostolova et al., 2012）. In particular, ventricular enlargement has been suggested as a structural biomarker for normal aging and progression of some illnesses, such as Alzheimer＇s disease （Blatter et al., 1995; Tang et al.,展开更多
This study was designed to evaluate the neuroprotective effects of Morinda citrifofia L. （Rubiaceae） commonly known as noni, and memantine （a N-methy-D-aspartate receptor inhibitor） on hydrocephalus-induced neurod...This study was designed to evaluate the neuroprotective effects of Morinda citrifofia L. （Rubiaceae） commonly known as noni, and memantine （a N-methy-D-aspartate receptor inhibitor） on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine （20 mg/kg, intraperitoneally; memantine-treated group） or noni （5 mL/kg, intragastrically; noni-treated group） was administered daily for 2 weeks. Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining density was significantly decreased in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3-positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle.展开更多
Periventricular nodular heterotopia （PNH） is a cortical malformation commonly found in epilepsy patients caused by the failure of neurons to migrate.Patients with PNH present with various clinical manifestations and...Periventricular nodular heterotopia （PNH） is a cortical malformation commonly found in epilepsy patients caused by the failure of neurons to migrate.Patients with PNH present with various clinical manifestations and genetic mutations. Despite their remarkable structural malformations, PNH patients generally have no neurological deficits or cognitive disabilities. However, particularly in patients with abnormal cortical development, the systematic abnormalities can also be severely delayed.展开更多
目的:探讨侧脑室周围白质软化症(periventricular leukomalacia,PVL)脑瘫患儿的临床及MRI特点。方法:从我院电子病历信息系统中回顾性提取自2011年1月1日至2021年12月31日在郑州大学第三附属医院儿童康复科住院康复的18岁以下脑瘫儿童信...目的:探讨侧脑室周围白质软化症(periventricular leukomalacia,PVL)脑瘫患儿的临床及MRI特点。方法:从我院电子病历信息系统中回顾性提取自2011年1月1日至2021年12月31日在郑州大学第三附属医院儿童康复科住院康复的18岁以下脑瘫儿童信息,比较和分析头颅MRI表现为PVL脑瘫患儿的孕周、出生体重、分型、粗大运动功能分级(gross motor function classification system,GMFCS)、共患病等方面的不同。结果:共纳入2012例脑瘫患儿,进行头颅MRI检查并有结果记录者共1419例,PVL共645例(45.45%),早产417例(64.65%),低出生体重患儿375例(58.14%);在有PVL分级结果的321例患儿中,PVL分级为Ⅱ级者在孕周<32周脑瘫患儿中占比最高,为72.53%(8/77),孕周与PVL分级有统计学差异(P<0.01);在出生体重方面,PVL分级为Ⅱ级者在出生体重1500~2500 g及<1500 g脑瘫患儿中占比分别为71.21%(94/132)和62.5%(25/40),不同出生体重儿的PVL分级分布差异均有统计学意义(P<0.05)。在型别方面,痉挛型双瘫占比57.36%(370/645),痉挛型四肢瘫占比17.36%(112/645);在GMFCS分级方面,具有独走能力者占比65.89%(425/645)。在有PVL分级结果的321例患儿中,PVL为Ⅲ级者痉挛型偏瘫占比最高,为53.49%(46/86),在GMFCS分级方面,PVL分级为Ⅱ级者GMFCS为Ⅰ、Ⅱ级者占比最低,为48.84%(105/215),型别、GMFCS分级与PVL分级之间差异均有统计学意义(P<0.01);在共患病方面,最后一次随访年龄>4岁的有505例,其中共患智力障碍181例(35.84%),共患癫痫78例(12.09%),共患视力障碍71例(11.01%)。在有PVL分级结果的321例患儿中,PVL分级为Ⅱ级者共患癫痫及智力障碍率均最高,分别为17.03%(31/182)和40.16%(49/122),PVL分级与是否共患癫痫及智力障碍均存在统计学差异(均P<0.05),PVL分级与是否共患听力障碍、视力障碍均无统计学意义(P>0.05)。结论:头颅MRI为PVL的脑瘫患儿的孕周、临床表现、合并症呈现一定的特点,头颅MRI可以为围产期预防、临床早期诊断、早期干预及减少后遗症提供重要依据。展开更多
AIM: To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP) and to find out whether any correlation exists between their occurance and etiologic factors.METHODS: Totally 194 pa...AIM: To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP) and to find out whether any correlation exists between their occurance and etiologic factors.METHODS: Totally 194 patients with the diagnosis of spastic type CP were enrolled in this retrospective study. Detailed ophthalmic examinations were performed. Demographic data and neuroradiological findings were documented. Kruskal-Wallis, Mann Whitney U, Pearson Chi-square tests and Student’s t tests were used in the statistical analysis.RESULTS: The mean age was 64.7±44.2 months on the first ophthalmic examination. Prevalences of diplegia (47.4%) and tetraplegia (36.1%) were found to be higher than the frequency of hemiplegia (16.5% ) in our study population. Etiologic factor was asphyxia in 60.8% of the patients. Abnormal ocular findings were present in 78.9% of the patients. Statistically significant poor vision was detected in tetraplegia group among all the spastic ubtypes of CP (P =0.000). Anisometropia and significant refractive error were found in 14.4% and 70.1% of the patients, respectively. Thirty-six children (18.6% ) had nystagmus and 107 children (55.2% ) had strabismus. Lower gestational age and birth weight were statistically higher in patients with esotropia than exotropia (P=0.009 and P =0.024, respectively). Abnormal morphology of the optic disc was present in 152 eyes (39.2% ). Severe periventricular leukomalacia (PVL) was found in 48 patients and statistically significant poor vision was detected in the presence of PVL (P =0.000).CONCLUSION:Spastic diplegic or tetraplegic CP patients with positive neuroradiological symptoms, younger gestational age and lower birth weight ought to have detailed ophthalmic examinations as early as possible to provide best visual rehabilitation.·展开更多
The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent...The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.展开更多
BACKGROUND： Neonatal cerebral palsy is mainly caused by prenatal factors. At present, an animal model of prenatal infection and early postnatal hypoxia does not exist. OBJECTIVE： To observe morphology and motor perf...BACKGROUND： Neonatal cerebral palsy is mainly caused by prenatal factors. At present, an animal model of prenatal infection and early postnatal hypoxia does not exist. OBJECTIVE： To observe morphology and motor performance following prenatal infection and hypoxic insult-induced brain damage of neonatal rats to verify the feasibility to establish a model of cerebral palsy. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratories of Xinjiang Center for Disease Control and Prevention from September 2007 to June 2008. MATERIALS： The hypoxic incubator was purchased from Shanghai Pediatric Medical Institute, China. Lipopolysaccharide （LPS, Escherichia coil, 055： B5） was purchased from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： A total of 27 Wistar rats, aged 7 days, were randomly assigned to sham-surgery group （n = 15） with no carotid artery incision or hypoxia treatment, hypoxia/ischemia （H/I） group （n = 12） undergoing ligature of the right common carotid artery followed by exposure to hypoxia at postnatal day 7 （P7）, and LPS/H group （n = 19）, in which pregnant rats were exposed in utero to LPS followed by prenatal hypoxia at embryonic day 16. MAIN OUTCOME MEASURES： Behavior, compound muscle action potential, and pathological changes were observed in 28-day-old rats. RESULTS： The footprint repeat space showed that left limb footprint repeatability in the H/I and LPS/H groups was lower than in the sham-surgery group （P 〈 0.05）. The space between the footprints was larger and unstable. Hind limb quadricep compound muscle action potential in the H/I and LPS/H groups showed lower wave amplitude compared with the sham-surgery group （P〈 0.05） Hematoxylin and eosin staining showed irregular cells around the ventricle, as well as periventricular leukomalacia. CONCLUSION： An animal model of cerebral palsy was established, which simulated the human condition most likely associated with occurrence of this disease. This model could be used for experimental studies related to cerebral palsy.展开更多
BACKGROUND： To date, animal models of white matter damage remain controversial. Mild grey matter damage should be the basis for animal models to investigate white matter disease. OBJECTIVE： To establish white matter...BACKGROUND： To date, animal models of white matter damage remain controversial. Mild grey matter damage should be the basis for animal models to investigate white matter disease. OBJECTIVE： To establish white matter damage in neonatal rats and evaluate feasibility of the established model by observing myelination and synaptic ultrastructure. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Guangzhou Medical College from December 2008 to May 2009. MATERIALS： H600 transmission electron microscopy was provided by Hitachi, Japan. METHODS： A total of 39 neonatal, Sprague Dawley rats were randomly assigned to normal control （n = 12）, sham-surgery （n = 12）, and white matter damage （n = 15） groups. White matter damage rats were subjected to right common carotid artery ligation, followed by inhalation of nitrogen oxygen gas mixture （6% oxygen） for 4 hours. MAIN OUTCOME MEASURES： Myelin sheath and synaptic ultrastructure in the injured （right） hippocampal CA1 region in 1-month-old rats were observed through the use of transmission electron microscopy, and pathological changes in the cerebral cortex and corpus callosum of the right hemisphere were detected by hematoxylin-eosin staining. RESULTS： Obvious tissue loss was observed in the corpus callosum of the injured （right） hemisphere. Injured oligodendrocytes and disrupted myelination were observed in the white matter damage group. However, synaptic length in the active zones, width of synaptic cleft, thickness of postsynaptic density, and curvature of the synaptic interface remained unchanged following injury, compared with the control and sham-surgery groups （P 〉 0.05）. CONCLUSION： The established white matter damage model resulted in changes in myelination and slightly altered synaptic ultrastructures. The model could function as an ideal model for white matter damage in neonatal rats.展开更多
Goal: The goal of this study is to define the epidemiological profile and identify the different brain lesions diagnosed in ultrasonography in preterm infants in Benin environment. Patients and methods: It is a prospe...Goal: The goal of this study is to define the epidemiological profile and identify the different brain lesions diagnosed in ultrasonography in preterm infants in Benin environment. Patients and methods: It is a prospective cross-sectional study of analytical aiming. It took place over a period of 6 months, from May 1<sup>st</sup> to October 31<sup>st</sup>, 2012 at the National Hospital University Centre Koutoukou Hubert Maga in neonatal units and medical scanning unit. It covered 105 premature newborn, classified into the very prematurity and the moderate prematurity. Results: The very premature represented 35.2% and the moderate premature 64.8%, with an average of 33.5% and 1.9 of standard deviation. The average age when implementing ultrasonographic transfontanellar was 7.2 ± 4.6 days old. The lowest birth weight was observed in very premature with p = 0.0025. The nasopharyngeal septum pellucidum was the most found lesions in 46 preterm infants (43.8%) with no statistically significantly difference in two groups, followed by the ventricular haemorrhage found in 21 preterm infants accounting for 20%, and the grade 1 or sub-ependymal haemorrhage prevailed in 14 premature accounting for 66.7%, afterward periventricular leukomalacia in 4 premature infants and hydrocephalus in 2 premature. Conclusion: The nasopharyngeal septum pellucidum and the sub-ependymal ventricular haemorrhage were the predominant anomalies in premature infants followed by leukomalacia.展开更多
基金supported by Lilling Family Neonatal Research Lab,Feinstein Institute for Medical Research
文摘Periventricular leukomalacia （PVL）, a white matter injury （WMI） affecting the premature infant＇s brain is commonly associated with ce- rebral palsy （CP）. Among premature infants 〈 1,500 g, approximately 7,000 develop CP yearly and 20,000-30,000 exhibit major cognitive deficits yearly （Volpe, 2009）. PVL results from hypoxia-ischemia （HI） with or without infection and is characterized by white matter necrotic lesions, hypomyelination, microglial activation, astrogliosis, and neuronal death. Risk factors for the development of PVL include： prematurity associated with immature cerebrovascular development, HI insults with lack of appropriate auto-regulation of cerebral blood flow, free radical production, energy deprivation, intrauterine infec- tion and chorioamnionitis. Affected infants show definitive signs of cerebral palsy such as spastic diplegia, seizures, developmental delay, visual and hearing impairment, scoliosis and incontinence by 6-9 months of age. PVL can also occur in term infants with certain con- genital cyanotic heart disease which will not be our focus here （Volpe, 2001）.
基金supported by Basic Science Research Program through the National Research Foundation of Korea (NRF)funded by the Ministry of Education, Science and Technology, No. 2012R1A1B4003477
文摘Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time （Bowen and Atwood, 2004; Grady, 2012）. Aging-related changes are typically accompanied by decline in cognitive function, urinary control, sensory-motor function, and gait ability （Bradley et al., 1991; Bowen and Atwood, 2004; Hedden and Gabrieli, 2004; Grady, 2012; Moran et al., 2012）. In addition, a number of studies have suggested changes in brain structure with normal aging, such as decrease in cortical thickness or increase in ventricular width （Blatter et al., 1995; Tang et al., 1997; Uylings and de Brabander, 2002; Preul et al., 2006; Apostolova et al., 2012）. In particular, ventricular enlargement has been suggested as a structural biomarker for normal aging and progression of some illnesses, such as Alzheimer＇s disease （Blatter et al., 1995; Tang et al.,
基金sponsored by a grant from the Education and Research Foundation of Faculty of Medicine,Kocaeli University,No.2009/45
文摘This study was designed to evaluate the neuroprotective effects of Morinda citrifofia L. （Rubiaceae） commonly known as noni, and memantine （a N-methy-D-aspartate receptor inhibitor） on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine （20 mg/kg, intraperitoneally; memantine-treated group） or noni （5 mL/kg, intragastrically; noni-treated group） was administered daily for 2 weeks. Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining density was significantly decreased in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3-positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle.
文摘Periventricular nodular heterotopia （PNH） is a cortical malformation commonly found in epilepsy patients caused by the failure of neurons to migrate.Patients with PNH present with various clinical manifestations and genetic mutations. Despite their remarkable structural malformations, PNH patients generally have no neurological deficits or cognitive disabilities. However, particularly in patients with abnormal cortical development, the systematic abnormalities can also be severely delayed.
文摘目的:探讨侧脑室周围白质软化症(periventricular leukomalacia,PVL)脑瘫患儿的临床及MRI特点。方法:从我院电子病历信息系统中回顾性提取自2011年1月1日至2021年12月31日在郑州大学第三附属医院儿童康复科住院康复的18岁以下脑瘫儿童信息,比较和分析头颅MRI表现为PVL脑瘫患儿的孕周、出生体重、分型、粗大运动功能分级(gross motor function classification system,GMFCS)、共患病等方面的不同。结果:共纳入2012例脑瘫患儿,进行头颅MRI检查并有结果记录者共1419例,PVL共645例(45.45%),早产417例(64.65%),低出生体重患儿375例(58.14%);在有PVL分级结果的321例患儿中,PVL分级为Ⅱ级者在孕周<32周脑瘫患儿中占比最高,为72.53%(8/77),孕周与PVL分级有统计学差异(P<0.01);在出生体重方面,PVL分级为Ⅱ级者在出生体重1500~2500 g及<1500 g脑瘫患儿中占比分别为71.21%(94/132)和62.5%(25/40),不同出生体重儿的PVL分级分布差异均有统计学意义(P<0.05)。在型别方面,痉挛型双瘫占比57.36%(370/645),痉挛型四肢瘫占比17.36%(112/645);在GMFCS分级方面,具有独走能力者占比65.89%(425/645)。在有PVL分级结果的321例患儿中,PVL为Ⅲ级者痉挛型偏瘫占比最高,为53.49%(46/86),在GMFCS分级方面,PVL分级为Ⅱ级者GMFCS为Ⅰ、Ⅱ级者占比最低,为48.84%(105/215),型别、GMFCS分级与PVL分级之间差异均有统计学意义(P<0.01);在共患病方面,最后一次随访年龄>4岁的有505例,其中共患智力障碍181例(35.84%),共患癫痫78例(12.09%),共患视力障碍71例(11.01%)。在有PVL分级结果的321例患儿中,PVL分级为Ⅱ级者共患癫痫及智力障碍率均最高,分别为17.03%(31/182)和40.16%(49/122),PVL分级与是否共患癫痫及智力障碍均存在统计学差异(均P<0.05),PVL分级与是否共患听力障碍、视力障碍均无统计学意义(P>0.05)。结论:头颅MRI为PVL的脑瘫患儿的孕周、临床表现、合并症呈现一定的特点,头颅MRI可以为围产期预防、临床早期诊断、早期干预及减少后遗症提供重要依据。
文摘AIM: To document common ocular abnormalities in children with spastic subtype of cerebral palsy (CP) and to find out whether any correlation exists between their occurance and etiologic factors.METHODS: Totally 194 patients with the diagnosis of spastic type CP were enrolled in this retrospective study. Detailed ophthalmic examinations were performed. Demographic data and neuroradiological findings were documented. Kruskal-Wallis, Mann Whitney U, Pearson Chi-square tests and Student’s t tests were used in the statistical analysis.RESULTS: The mean age was 64.7±44.2 months on the first ophthalmic examination. Prevalences of diplegia (47.4%) and tetraplegia (36.1%) were found to be higher than the frequency of hemiplegia (16.5% ) in our study population. Etiologic factor was asphyxia in 60.8% of the patients. Abnormal ocular findings were present in 78.9% of the patients. Statistically significant poor vision was detected in tetraplegia group among all the spastic ubtypes of CP (P =0.000). Anisometropia and significant refractive error were found in 14.4% and 70.1% of the patients, respectively. Thirty-six children (18.6% ) had nystagmus and 107 children (55.2% ) had strabismus. Lower gestational age and birth weight were statistically higher in patients with esotropia than exotropia (P=0.009 and P =0.024, respectively). Abnormal morphology of the optic disc was present in 152 eyes (39.2% ). Severe periventricular leukomalacia (PVL) was found in 48 patients and statistically significant poor vision was detected in the presence of PVL (P =0.000).CONCLUSION:Spastic diplegic or tetraplegic CP patients with positive neuroradiological symptoms, younger gestational age and lower birth weight ought to have detailed ophthalmic examinations as early as possible to provide best visual rehabilitation.·
基金The Cell Culture Core supported by grant No.PP1498:Neural Cell Culture Core and NIH grant No.04612 Intellectual&Developmental Disabilities.The Cell,Circuits and Systems Analysis Core is supported by NICHD award No.U54HD087101-03
文摘The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.
基金the National Natural Science Foundation of China,No.30960393Key Foundation in Science and Technology of Xinjiang Uygur Autonomous Region,No.200633128(2)the Youth Science and Technology Foundation of Health Department of Xinjiang Uygur Autonomous Region,No.2007Y26
文摘BACKGROUND： Neonatal cerebral palsy is mainly caused by prenatal factors. At present, an animal model of prenatal infection and early postnatal hypoxia does not exist. OBJECTIVE： To observe morphology and motor performance following prenatal infection and hypoxic insult-induced brain damage of neonatal rats to verify the feasibility to establish a model of cerebral palsy. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratories of Xinjiang Center for Disease Control and Prevention from September 2007 to June 2008. MATERIALS： The hypoxic incubator was purchased from Shanghai Pediatric Medical Institute, China. Lipopolysaccharide （LPS, Escherichia coil, 055： B5） was purchased from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： A total of 27 Wistar rats, aged 7 days, were randomly assigned to sham-surgery group （n = 15） with no carotid artery incision or hypoxia treatment, hypoxia/ischemia （H/I） group （n = 12） undergoing ligature of the right common carotid artery followed by exposure to hypoxia at postnatal day 7 （P7）, and LPS/H group （n = 19）, in which pregnant rats were exposed in utero to LPS followed by prenatal hypoxia at embryonic day 16. MAIN OUTCOME MEASURES： Behavior, compound muscle action potential, and pathological changes were observed in 28-day-old rats. RESULTS： The footprint repeat space showed that left limb footprint repeatability in the H/I and LPS/H groups was lower than in the sham-surgery group （P 〈 0.05）. The space between the footprints was larger and unstable. Hind limb quadricep compound muscle action potential in the H/I and LPS/H groups showed lower wave amplitude compared with the sham-surgery group （P〈 0.05） Hematoxylin and eosin staining showed irregular cells around the ventricle, as well as periventricular leukomalacia. CONCLUSION： An animal model of cerebral palsy was established, which simulated the human condition most likely associated with occurrence of this disease. This model could be used for experimental studies related to cerebral palsy.
基金the Science and Technology Program of Medical Health of Guang-zhou, No. 2008-YB-173a Grant from Guangdong Provincial Health Depart-ment, No. A2009271
文摘BACKGROUND： To date, animal models of white matter damage remain controversial. Mild grey matter damage should be the basis for animal models to investigate white matter disease. OBJECTIVE： To establish white matter damage in neonatal rats and evaluate feasibility of the established model by observing myelination and synaptic ultrastructure. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Guangzhou Medical College from December 2008 to May 2009. MATERIALS： H600 transmission electron microscopy was provided by Hitachi, Japan. METHODS： A total of 39 neonatal, Sprague Dawley rats were randomly assigned to normal control （n = 12）, sham-surgery （n = 12）, and white matter damage （n = 15） groups. White matter damage rats were subjected to right common carotid artery ligation, followed by inhalation of nitrogen oxygen gas mixture （6% oxygen） for 4 hours. MAIN OUTCOME MEASURES： Myelin sheath and synaptic ultrastructure in the injured （right） hippocampal CA1 region in 1-month-old rats were observed through the use of transmission electron microscopy, and pathological changes in the cerebral cortex and corpus callosum of the right hemisphere were detected by hematoxylin-eosin staining. RESULTS： Obvious tissue loss was observed in the corpus callosum of the injured （right） hemisphere. Injured oligodendrocytes and disrupted myelination were observed in the white matter damage group. However, synaptic length in the active zones, width of synaptic cleft, thickness of postsynaptic density, and curvature of the synaptic interface remained unchanged following injury, compared with the control and sham-surgery groups （P 〉 0.05）. CONCLUSION： The established white matter damage model resulted in changes in myelination and slightly altered synaptic ultrastructures. The model could function as an ideal model for white matter damage in neonatal rats.
文摘Goal: The goal of this study is to define the epidemiological profile and identify the different brain lesions diagnosed in ultrasonography in preterm infants in Benin environment. Patients and methods: It is a prospective cross-sectional study of analytical aiming. It took place over a period of 6 months, from May 1<sup>st</sup> to October 31<sup>st</sup>, 2012 at the National Hospital University Centre Koutoukou Hubert Maga in neonatal units and medical scanning unit. It covered 105 premature newborn, classified into the very prematurity and the moderate prematurity. Results: The very premature represented 35.2% and the moderate premature 64.8%, with an average of 33.5% and 1.9 of standard deviation. The average age when implementing ultrasonographic transfontanellar was 7.2 ± 4.6 days old. The lowest birth weight was observed in very premature with p = 0.0025. The nasopharyngeal septum pellucidum was the most found lesions in 46 preterm infants (43.8%) with no statistically significantly difference in two groups, followed by the ventricular haemorrhage found in 21 preterm infants accounting for 20%, and the grade 1 or sub-ependymal haemorrhage prevailed in 14 premature accounting for 66.7%, afterward periventricular leukomalacia in 4 premature infants and hydrocephalus in 2 premature. Conclusion: The nasopharyngeal septum pellucidum and the sub-ependymal ventricular haemorrhage were the predominant anomalies in premature infants followed by leukomalacia.
