Intrauterine Fetal Constraint Induces Chondrocyte Apoptosis and Premature Ossification of the Cranial Base

Smartt, James M.; Karmacharya, Jagajan; Gannon, Francis H.; Teixeira, Cristina; Mansfield, Kyle D.; Hunenko, Oksana; Shapiro, Irving M.; Kirschner, Richard E.

doi:10.1097/01.prs.0000182224.98761.cf

Cited by 32 publications

(10 citation statements)

References 37 publications

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“…Graham and Smith described two cases of metopic synostosis believed to be the result of limited space for the fetal head (one was jammed in a bicornuate uturus, the other one between the legs of his two siblings) [34]. More recently this theory was supported by Smartt et al, proving the principle in a mouse model [90].

Intrinsic brain malformation

…”

Section: Etiologymentioning

confidence: 99%

Metopic synostosis

Meulen

2012

Childs Nerv Syst

139

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Premature closure of the metopic suture results in a growth restriction of the frontal bones, which leads to a skull malformation known as trigonocephaly. Over the course of recent decades, its incidence has been rising, currently making it the second most common type of craniosynostosis. Treatment consists of a cranioplasty, usually preformed before the age of 1 year. Metopic synostosis is linked with an increased level of neurodevelopmental delays. Theories on the etiology of these delays range from a reduced volume of the anterior cranial fossa to intrinsic malformations of the brain. This paper aims to provide an overview of this entity by giving an update on the epidemiology, etiology, evolution of treatment, follow-up, and neurodevelopment of metopic synostosis.

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Intrinsic brain malformation

…”

Section: Etiologymentioning

confidence: 99%

Metopic synostosis

Meulen

2012

Childs Nerv Syst

139

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“…Craniosynostosis has an incidence of approximately 1 in 2500 live births, and may be syndromic or isolated (Mooney et al, 1998;Ridgway and Weiner, 2004;Smartt et al, 2005;Ferreira et al, 2006;Kobus et al, 2007;Maltese et al, 2007;Di Rocco et al, 2009;Mackenzie et al, 2009;Kolar, 2011). It can cause intracranial hypertension, and, in syndromic cases, morbidity may be increased further due to exophthalmos, obstructive airway disease, and other comorbidities (Kapp-Simon et al, 2005;Di Rocco et al, 2009;Scott et al, 2009).…”

Section: Introductionmentioning

confidence: 96%

Development and testing of an absorbable spring for cranial expansion in rabbits

Faller

Santos

Marques

et al. 2015

Journal of Cranio-Maxillofacial Surgery

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“…They demonstrated that mechanical forces caused by intrauterine cerclage up-regulates TGF-ß1 in osteoblasts of the involved cranial suture and downregulates its dural TGF-ß3 4,6 . This phenomenon associated to chondrocyte apoptosis was also seen in the spheno-occipital synchondrosis, suggesting morphologic skeletal changes in the cranial base sutures 7 . These experimental studies corroborate other clinical studies which suggest that non syndromic forms of craniosynostosis might have started in the primary premature fusion of the cranial base sutures [8][9][10][11] .…”

Section: Discussionmentioning

confidence: 84%

Effects of uterine cervix constriction on Wistar rats

Raposo-Amaral¹,

Almeida²,

Raposo‐Amaral³

et al. 2010

Acta Cir. Bras.

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Purpose:To verify if uterine cerclage can induce craniosynostosis or any cranial deformity in new born Wistar rats. Methods: One pregnant female Wistar rat underwent laparotomy on day 18 of gestation and the uterus cervix was closed with a 3-0 nylon suture to avoid delivery, that occurs normally on the 21 day. The suture was released after 48 hours beyond the normal gestation period. The female rat delivered 11 pups. Six surviving rats from the delivery (group A -constrained group). Two rats were born from another mother and in the same age were used as control group (group B -2 nonconstrained controls) were allowed to grow. They were sacrificed 1.2 years after their birth all the eight animals. Linear measurement, routine histology and computed tomography of the skull were performed at the time of their death to evaluate the cranial asymmetries by mesurements of the anatomical landmarks of the craniofacial skeleton of the rats on the two groups and compared then. Results: We did not observe statistically significant differences in any of the compared measurements (p>0.05) obtained through the morphologic and radiologic methods. Histologic examinations did not reveal any sign of premature fusion or suture imbrications. Critical decrease in longitudinal body size was noticed as the limbs too in all the animals of group A. Conclusion: Constriction of uterine cervix leads to fetus suffering, even death for a few animals, associated to small body size, but not to craniosynostosis. Key words: Craniosynostoses. Cerclage, Cervical. Surgery, Plastic. Rats. RESUMOObjetivo: Verificar se a cerclagem intra-uterina pode induzir, ao nascimento de ratos Wistar, craniossinostose ou qualquer outra deformidade craniana. Métodos: Uma rata Wistar prenhe foi submetida à laparotomia no 18º dia de gestação e o cérvix uterino foi suturado com 3-0 nylon, impedindo o parto normal que normalmente ocorre no 21º dia de gestação. A sutura foi liberada 48 horas após o período gestacional normal. A rata gestante deu à luz 11 animais. Seis ratos sobreviveram ao parto (grupo A com restrição). Dois ratos nascidos de outra mãe e com a mesma idade foram utilizados como controle (grupo B sem restrição controle) durante o seu crescimento. Os oito animais foram sacrificados após 1,2 ano. Medidas lineares, histologia e tomografia computadorizada foram utilizadas para a aferição de assimetrias cranianas através da mensuração de pontos anatômicos do esqueleto craniofacial dos ratos dos dois grupos. Resultados: Não foi observada diferença estatisticamente significante entre as medidas obtidas nos ratos dos dois grupos (p>0,05) obtidas através de métodos morfológicos e radiológicos. As análises histológicas não revelaram sinais de fusão prematura da suturas do crânio. Diminuição do segmento corpóreo, bem como do tamanho dos membros foi evidenciado em todos os animais do grupo A. Conclusão: A restrição do cérvix uterino levou ao sofrimento fetal, morte de alguns animais e diminuição do tamanho do corpo de todos os animais, mas não craniossinostose....

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Intrauterine Fetal Constraint Induces Chondrocyte Apoptosis and Premature Ossification of the Cranial Base

Abstract: These experiments confirm the ability of intrauterine constraint to induce changes in the morphology and cell biology of the cranial base in synostotic fetuses.

Cited by 32 publications

References 37 publications

Metopic synostosis

Metopic synostosis

Development and testing of an absorbable spring for cranial expansion in rabbits

Effects of uterine cervix constriction on Wistar rats

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