Reduction in neural injury with earlier delivery in a mouse model of congenital myelomeningocele

Al-Shanafey, Saud; Fontecha, César G.; Aguirre-Canyadell, Màrius; Soldado, Francisco; Rojo, Alejandro A.; Conesa, Xavier; Torán, Núria; Ibanez, Vicenç M.; Peiró, José L.

doi:10.3171/2013.7.peds1351

Cited by 7 publications

(9 citation statements)

References 31 publications

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“…In spina bifida the fetal spinal cord is exposed to the enzymatic action of amniotic fluid 3 . Chemical and physical erosion result in loss of neural tissue, both aggravating the primary lesion and changing the cytoarchitecture of the spinal cord 13 .…”

Section: Discussionmentioning

confidence: 99%

“…However, disruption of the CD200-CD200R signaling can cause microglial over reactivity 9 – 12 . In spina bifida the loss of neural tissue 2 , 13 can disrupt the CD200-CD200R ratio, thus leading to over activation of the microglia, induction of the neuroinflammatory process, and neurodegeneration 14 , 15 . Knowing the exhisting neural tissue damage in utero in spina bifida and given the importance of this immune ligand-receptor system in regulating microglial expression during brain development and microglial priming; we hypothezised that spina bifida suffer a progressive astrroglial and microglial activation during gestation and the microglia priming may be related to the alteration of the CD200-CD200R system.…”

Section: Introductionmentioning

confidence: 99%

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CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

Oria¹,

Figueira²,

Scorletti³

et al. 2018

Sci Rep

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Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine environment. Astrogliosis in exposed spinal cords has been described in animal models of spina bifida during embryonic life but its relationship with neuroinflammatory processes are completely unknown. Using a retinoic acid-induced rat model of spina bifida we demonstrated that, when exposed to amniotic fluid, fetal spinal cords showed progressive astrogliosis with neuronal loss at mid-gestation (E15) compared to unexposed spinal cords. The number of microglial cells with a reactive phenotype and activation marker expression increased during gestation and exhibited progressive disruption in the inhibitory immune ligand-receptor system. Specifically we demonstrate down-regulation of CD200 expression and up-regulation of CD200R. Exposed spinal cords demonstrated neuroinflammation with increased tissue water content and cytokine production by the end of gestation (E20), which correlated with active Caspase3 expression in the exposed layers. Our findings provide new evidence that microglia activation, including the disruption of the endogenous inhibitory system (CD200-CD200R), may participate in the pathogenesis of spina bifida through late gestation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

Oria¹,

Figueira²,

Scorletti³

et al. 2018

Sci Rep

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“…Animal studies demonstrate that exposure of the spinal cord to the intra‐uterine environment results in significant acquired neural tissue damage. Chemical and physical damage of the exposed tissue result in loss of neural tissue, aggravating the primary lesion and changing the cytoarchitecture of the spinal cord 39 . The progressive deterioration of the spinal tissue from the early stage of gestation onwards may lead to a definitive loss of neurological function persisting after the prenatal repair and the reversal HBH and/or ventriculomegaly and may explain why we did not find brain imaging predictors of motor outcomes at birth.…”

Section: Discussionmentioning

confidence: 81%

Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?

et al. 2021

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Objective: To determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD). Methods: Retrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open-hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL.Results: 26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2-42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth. Conclusions: HBH below C1 before surgery was associated with a worse functional level than anatomical level at birth. Key pointsWhat's already known about this topic? � Signs of severe ventricular dilatation or hindbrain herniation (HBH) prior to prenatal repair have been proposed as predictors of the need for postnatal ventriculoperitoneal shunting.� Detailed in-utero MRI assessment of HBH 6 weeks after prenatal neural tube defect repair can independently predict the need for postnatal hydrocephalus treatment.Romain Corroenne and Alexander Zarutskie contributed equally for the development of this manuscript.

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“…3 The exposure of the neural elements is associated with progressive injury, aggravating the primary insult and changing the cytoarchitecture of the spinal cord. 1,[3][4][5][6][7] As a consequence, ONTDs are associated with motor and sensory deficits. [3][4][5][6]8 Oliver et al demonstrated that cystic lesions, prenatally or postnatally repaired, are associated with fetal talipes and that these were more frequent with increasing sac size.…”

Section: Introductionmentioning

confidence: 99%

Impact of the cystic neural tube defects on fetal motor function in prenatal myelomeningocele repairs: A retrospective cohort study

et al. 2021

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Objective: To determine the impact of the lesion type (cystic [myelomeningocele] or flat [myeloschisis]) on the fetal motor function (MF) in cases candidates for prenatal open neural tube defect (ONTD) repair. Methods: Retrospective cohort study of patients with ONTD who underwent prenatal repair at a single institution between 2011 and 2019. The lesion type and the measurements of the length and width of the lesions to calculate the surface of the ellipsoid lesion were performed using MR scans. Prenatal MF of the lower extremities was evaluated by ultrasound following a metameric distribution at the time of referral. Intact MF was defined as the observation of plantar flexion of the ankle. Logistic regression was performed to determine the predictive value of the type of lesion for having an intact MF at the time of referral.Results: 103 patients were included at 22.9 (19-25.4) weeks; 65% had cystic and 35% had flat lesions. At the time of referral, there was a higher proportion of cases with an intact MF in the presence of flat lesions (34/36; 94.4%) as compared to cystic lesion (48/67; 71.6%, p < 0.01). When adjusting for gestational age and anatomical level of the lesion, flat ONTD were 3.1 times more likely to be associated by intact motor function (CI%95 [2.1-4.6], p < 0.01) at the time of referral. Conclusion:Cystic ONTD are more likely to be associated with impaired MF at midgestation in candidates for prenatal ONTD repair. Key pointsWhat's already known about this topic? � The diagnosis of open neural tube defect is associated with motor and sensory deficit. Open neural tube defects can be divided into two phenotypes: cystic (myelomeningocele) and flat (myeloschisis) lesions.

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Reduction in neural injury with earlier delivery in a mouse model of congenital myelomeningocele

Cited by 7 publications

References 31 publications

CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?

Impact of the cystic neural tube defects on fetal motor function in prenatal myelomeningocele repairs: A retrospective cohort study

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