RESUMO
White matter injury in premature infants is known to be major cause of long-term neurocognitive disability, but the pathogenic mechanism remains unclear, hampering our ability to develop preventions. Periventricular leukomalacia is a severe form of white matter injury. In the present study, we explored the effects of cerebral ischemia and/or intrauterine inflammation on the development of oligodendroglia in the cerebral white matter using chronically instrumented fetal sheep. Each fetus received one of three insults: hemorrhage, inflammation and their combination. In the hemorrhage group, 40% of the fetoplacental blood volume was acutely withdrawn, and 24 hours after removal, the blood was returned to the fetus. The inflammation group received intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin and thus suffered from necrotizing funisitis and chorioamnionitis. The inflammatory hemorrhage group underwent acute hemorrhage under the inflammatory state. The sham group received no insults. Importantly, periventricular leukomalacia was not detected in the sham and the inflammation groups. Differentiating oligodendroglia at various developmental stages were identified by immunohistochemical analysis with specific antibodies. No difference in the density of oligodendroglial progenitors was detected among the four groups, whereas oligodendroglial precursors were significantly reduced in the three insult groups, compared to sham control. Moreover, the density of immature oligodendroglia was higher in the inflammation group and the inflammatory hemorrhage group, while the density of mature oligodendroglia was highest in the hemorrhage group. We propose that cerebral ischemia or intrauterine inflammation induces the differentiation of oligodendroglial precursors in preterm fetuses, eventually resulting in their exhaustion.
Assuntos
Isquemia Encefálica/embriologia , Isquemia Encefálica/patologia , Diferenciação Celular , Feto/patologia , Inflamação/patologia , Oligodendroglia/patologia , Nascimento Prematuro/patologia , Substância Branca/patologia , Animais , Anticorpos/metabolismo , Apoptose , Astrócitos/patologia , Isquemia Encefálica/complicações , Contagem de Células , Linhagem da Célula , Feminino , Imuno-Histoquímica , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/embriologia , Hemorragias Intracranianas/patologia , Lectinas/metabolismo , Leucomalácia Periventricular/complicações , Leucomalácia Periventricular/embriologia , Leucomalácia Periventricular/patologia , Microglia/patologia , Modelos Biológicos , Ovinos , Substância Branca/embriologiaRESUMO
OBJECTIVE: The purpose of this study is to define the role of foetal magnetic resonance imaging (MRI) in evaluating cerebral ischaemic-haemorrhagic lesions and the extension of parenchymal injuries. STUDY DESIGN: From September 2006 to September 2010, 271 foetal MRI have been performed on cases referred to us for ultrasound suspect of brain abnormalities or cytomegalovirus infection and Toxoplasma serum conversion. Foetal MRI was performed with a 1.5-T magnet system without mother sedation. RESULTS: Foetal MRI detected ischaemic-haemorrhagic lesions in 14 of 271 foetuses, consisting of 5% incidence. MRI confirmed the diagnosis in three of 14 cases with ultrasonography (US) suspect of ischaemic-haemorrhagic lesions associated with ventriculomegaly. In one of 14 cases with US findings of cerebellar haemorrhage, MRI confirmed the diagnosis and provided additional information regarding the parenchymal ischaemic injury. In eight of 14 cases with US suspect of ventriculomegaly (3), corpus callosum agenesis (2), hypoplasia of cerebellar vermis (1), holoprosencephaly (1) and spina bifida (1), MRI detected ischaemic and haemorrhagic lesions unidentified at US examination. In two of 14 foetuses with US suspect of intracerebral space-occupying lesion, MRI modified the diagnosis to extra-axial haematoma associated with dural sinus malformation. Results were compared with post-mortem findings or afterbirth imaging follow-up. CONCLUSIONS: Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.
Assuntos
Isquemia Encefálica/embriologia , Hemorragia Cerebral/embriologia , Doenças Fetais/diagnóstico , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal/métodos , Anormalidades Múltiplas , Adulto , Agenesia do Corpo Caloso/diagnóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Doenças Cerebelares/diagnóstico , Cerebelo/anormalidades , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/patologia , Infecções por Citomegalovirus/diagnóstico , Anormalidades do Olho/diagnóstico , Feminino , Doenças Fetais/patologia , Idade Gestacional , Holoprosencefalia/diagnóstico , Humanos , Doenças Renais Císticas/diagnóstico , Gravidez , Retina/anormalidades , Disrafismo Espinal/diagnósticoRESUMO
PURPOSE OF REVIEW: Advances in cardiac surgical techniques and intensive care have led to improved survival in babies with congenital heart disease (CHD). Although it is true that the majority of children with CHD today survive, many have impaired neurodevelopmental outcome. Although continuing to improve short-term morbidity and mortality are important goals, recent research has focused on defining the impact of CHD on brain development and brain injury in utero. RECENT FINDINGS: The impact of CHD on the developing brain of the fetus and infant will be discussed. Neurologic abnormalities detectable prior to surgery will be described and postnatal progression of abnormalities will be highlighted. Potential causes of these findings will be discussed, including altered cerebral blood flow in utero, and brain development and risk for in-utero and postnatal brain injury. Finally, neurologic and developmental outcome after surgical repair of CHD will be reviewed. SUMMARY: Neurodevelopmental evaluation preoperatively and postoperatively in CHD patients should be standard practice, not only to identify those with impairments who would benefit from intervention services but also to identify risk factors and strategies to optimize outcome. Fetal management and intervention strategies for specific defects may ultimately play a role in improving in-utero hemodynamics and increasing cerebral oxygen delivery to enhance brain development.
Assuntos
Encéfalo/embriologia , Cardiopatias Congênitas/complicações , Encéfalo/anormalidades , Encéfalo/irrigação sanguínea , Isquemia Encefálica/embriologia , Desenvolvimento Fetal , Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/cirurgia , Humanos , Resultado do TratamentoRESUMO
AIMS: To assess optic disc characteristics in premature infants with and without ischaemic brain injury and to evaluate the role of optic disc morphology in dating the injury. METHODS: RetCam fundal images, cranial ultrasounds and magnetic resonance imaging (MRI) of 109 premature infants were analysed. The study cohort was divided into subgroups depending on the presence or absence of periventricular leucomalacia (PVL) and intraventricular haemorrhage (IVH). The control group consisted of infants with normal neuroimaging at term and 2 years of age. Using the image analysis software of the RetCam, optic disc diameter (ODD), optic disc area (ODA), and optic cup area (OCA) were measured at 33-34 weeks gestational age. As serial cranial ultrasonography had been performed, it was possible to date the brain injury in those infants with periventricular white matter (PVWM) damage. RESULTS: Although there was a trend towards reducing ODD, ODA, and OCA with increasing severity of IVH, only the IVH 4 group differed significantly from the controls for these parameters (p = 0.002, p = 0.02, and p = 0.04, respectively). 44.4% of infants with grade 4 IVH had small discs. Only one patient had a large cup in a normal sized disc; this patient had IVH 4. In patients with PVWM damage, the median time of insult was 27 weeks in those with small discs and 28 weeks in those with normal discs. This difference was not significant (p = 0.23). CONCLUSIONS: Premature infants with IVH 4 have an increased incidence of optic nerve hypoplasia. We found no association between disc morphology and timing of brain injury.
Assuntos
Isquemia Encefálica/patologia , Doenças do Prematuro/patologia , Disco Óptico/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/embriologia , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Recém-Nascido , Recém-Nascido Prematuro , Leucomalácia Periventricular/diagnóstico por imagem , Leucomalácia Periventricular/embriologia , Leucomalácia Periventricular/patologia , Masculino , UltrassonografiaRESUMO
BACKGROUND AND PURPOSE: Little is known about the different patterns of fetal cerebral ischemic lesions at MR imaging. Our purpose was to evaluate the contribution of MR imaging in the evaluation of such lesions by correlating the results with ultrasonography (US) and neurofetopathologic (NFP) findings. METHODS: We examined 28 fetuses (mean, 28 weeks' gestation) with cerebral ischemic lesions on NFP examination. MR findings were correlated with US and NFP results with regard to the depiction of gyration and parenchymal abnormalities. RESULTS: MR imaging added to US findings in 24 cases by revealing lesions (gyration abnormalities, parenchymal lesions). These results were either overlooked during US (n = 16) or more extensive than expected with US (n = 8). MR findings were always confirmed by NFP. NFP yielded additional findings for 14 lesions that were overlooked during MR imaging (n = 4) or that were more extensive than expected with MR imaging (n = 10). T1-, T2-, and T2*-weighted MR patterns of different lesions (cavitations, gliosis, softening of the white matter, laminar necrosis, calcified leukomalacia, old hemorrhage) were identified. CONCLUSION: MR imaging is a valuable tool in the evaluation of fetal brain ischemia. The results of this study emphasize the role of the different sequences (T1-, T2-, T2*-weighted) required to detect fetal cerebral ischemic lesions. MR imaging is more accurate in the detection of small focal lesions than in the evaluation of diffuse white matter abnormalities.
Assuntos
Isquemia Encefálica/embriologia , Encéfalo/embriologia , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Encéfalo/patologia , Dano Encefálico Crônico/embriologia , Dano Encefálico Crônico/patologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/embriologia , Hemorragia Cerebral/patologia , Feminino , Gliose/diagnóstico , Gliose/embriologia , Gliose/patologia , Humanos , Recém-Nascido , Leucomalácia Periventricular/diagnóstico , Leucomalácia Periventricular/embriologia , Leucomalácia Periventricular/patologia , Masculino , Necrose , Gravidez , Prognóstico , Sensibilidade e Especificidade , Estatística como Assunto , Ultrassonografia Pré-NatalRESUMO
Previous work in this laboratory has demonstrated that cerebral hypoperfusion increases the expression of prostaglandin endoperoxide synthase-2 (PGHS-2) in ovine fetal brain regions. Endogenously produced prostaglandins, in turn, partially mediate the fetal hypothalamus- pituitary-adrenal (HPA) axis response to arterial hypotension. In separate experiments, we have found that oestradiol stimulates fetal HPA axis activity. The present experiments were designed to test the hypothesis that oestradiol increases the expression of PGHS isoforms, and that oestradiol augments the PGHS response to cerebral hypoperfusion. Sixteen fetal sheep of known gestational ages (124-128 days' gestation at the time of study) were subjected to chronic catheterization and implantation of extravascular occluder around the brachiocephalic artery. Eight fetuses were subjected to subcutaneous implantation of a pellet containing 17beta-oestradiol (release rate 5 mg (21 days)-1). Brachiocephalic occlusion (BCO) stimulated adrenocorticotropin (ACTH), cortisol and arginine vasopressin (AVP) secretion, responses that were augmented by oestradiol. One hour after the beginning of a 10 min period of BCO, PGHS-1 mRNA was increased in fetal brainstem and hypothalamus, and PGHS-2 mRNA was increased in fetal brainstem. Oestradiol, by itself, increased the abundance of PGHS-2 mRNA in brainstem and cerebellum, and augmented the PGHS-2 mRNA response to BCO in brainstem. In contrast, oestradiol had no significant effect on the abundance of PGHS-1 mRNA in any brain region. PGHS-1 and PGHS-2 protein levels did not reflect the changes in the respective mRNAs. The abundance of both proteins was increased in cerebral cortex in response to BCO, and the abundance of PGHS-2 protein was increased by both oestradiol and BCO in the hippocampus. The results of this study confirm and extend the results of our previous studies, demonstrating an effect of cerebral hypoperfusion on the expression of both isoforms of PGHS. We conclude that oestradiol increases the expression of PGHS-2 in specific fetal brain regions, and that there is an interaction between oestradiol and BCO in the control of PGHS-2 expression in the fetal brainstem. We expect that at later time-points, the changes in mRNA would be followed by similar changes in enzyme abundance at the protein level. We speculate that at least a part of the effect of oestradiol on fetal HPA axis function is mediated by an interaction between oestradiol and prostaglandin biosynthesis in the fetal brain.
Assuntos
Isquemia Encefálica/embriologia , Encéfalo/embriologia , Estradiol/farmacologia , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Sangue Fetal , Feto/metabolismo , Idade Gestacional , Hidrocortisona/sangue , Isoenzimas/genética , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/metabolismo , Ovinos , Distribuição TecidualRESUMO
Intracerebral administration of [3H]arachidonic acid ([3H]ArA) into 19-20-day-old rat embryos, resulted in a rapid incorporation of label into brain lipids. One hour after injection, 55.6 +/- 8.2, 18.0 +/- 3.4, and 13.7 +/- 1.3% of the total radioactivity was associated with phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, respectively. Approximately 10% of radioactivity was found acylated in neutral lipids of which free ArA comprised only 1.5 +/- 0.2% of the total radioactivity. Complete restriction of the maternal-fetal circulation for < or = 40 min did not affect the rate of [3H]ArA incorporation (t1/2 = 2 min) into fetal brain lipids, suggesting an effective acylation mechanism that proceeds irrespective of the impaired blood flow. After a short restriction period (5 min), the radioactivity in diacylglycerol was elevated by 50%. After a longer restriction period (20 min), the radioactivity in the free fatty acid and diacylglycerol fractions increased to values of 130 and 87%, respectively. Polyphosphoinositides prelabeled with either [3H]ArA or 32P were rapidly degraded after 5 min of ischemia. After 20 min, the decrease in phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate radioactivity was 47 and 70%, respectively. Double labeling of phospholipids with [14C]palmitic acid and [3H]ArA indicated a preferential loss of [3H]ArA within the polyphosphoinositide species after 20 min, but not after 5 min of ischemia. The specific activity of [14C]palmitate remained unchanged. The current data suggest phospholipase C-mediated diacylglycerol formation at the beginning of the insult followed by a phospholipase A2-mediated ArA liberation at a later time, both enzymes presumably acting preferentially on polyphosphoinositide species.
Assuntos
Ácidos Araquidônicos/metabolismo , Isquemia Encefálica/metabolismo , Diglicerídeos/metabolismo , Fosfatidilinositóis/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Animais , Ácidos Araquidônicos/administração & dosagem , Encéfalo , Isquemia Encefálica/embriologia , Isquemia Encefálica/enzimologia , Ativação Enzimática/fisiologia , Feminino , Feto , Injeções Intraventriculares , Fosfatidilcolinas/metabolismo , Fosfatos de Fosfatidilinositol , Fosfatidilinositóis/classificação , Gravidez , Proteína Quinase C/metabolismo , Proteína Quinase C/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
Connatal periventricular pseudocysts are important sequelae of different noxious insults in the developing brain. Accurate diagnosis of those pathologic entities during early life has therefore become of direct concern to the clinician. Our experience with 12 infants of connatal periventricular pseudocysts provides the basis of this study. They belonged to different pathological entities: focal paraventricular pseudocysts (5 cases), subependymal pseudocyst (3 cases), connatal viral infection (3 cases), and chromosomal abnormality (1 case). When present at birth, they suggest an intrauterine pathology. It has only been with the advent of real-time cranial ultrasound that periventricular pseudocystic lesions can be detected in neonates following an abnormal pregnancy. Some obstetric complications during the second trimester can cause paraventricular or subependymal pseudocyst in the foetus. Neurotrophic viral infection and chromosomal abnormalities have also been implicated in the production of cystic lesions in this region. These lesions are not a terminal event in infants but may be a condition of major clinical importance for further neurological development.
Assuntos
Ventrículos Cerebrais/diagnóstico por imagem , Cistos/congênito , Cistos/diagnóstico por imagem , Encefalopatias/congênito , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Isquemia Encefálica/embriologia , Hemorragia Cerebral/embriologia , Cistos/etiologia , Ecoencefalografia , Feminino , Doenças Fetais , Humanos , Recém-Nascido , Gravidez , Complicações na GravidezRESUMO
Changes in the levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) have been measured in brains of 20-day-old rat fetuses exposed to global intrauterine ischemia. Ischemia of different duration (0.5-30 minutes) did not alter the level of cAMP. In contrast, cGMP levels increased as a result of ischemia. This increase was seen even after a short period of ischemia (less than 5 minutes) and was maximal after 5 minutes, where a threefold increase could be observed. This stimulation was transient: after 30 min of ischemia, cGMP returned to the control level. Accumulation of cGMP can be related to the activation of guanylate cyclase, the activity of which is doubled after 15 minutes of ischemia. Immunoprecipitation of guanylate cyclase after in vivo labeling of the fetal brain with 32Pi revealed a threefold increase in the phosphorylation of the enzyme after 15 minutes of ischemia. The possible role of these modifications in cGMP metabolism during the course of ischemia is discussed.