Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for Fetal Surgery

George, Timothy M.; Fuh, Eric

doi:10.1159/000071319

Cited by 17 publications

(15 citation statements)

References 29 publications

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“…The investigation herein confirms that the ct/lp mutant mouse is an adequate animal model to obtain MMC-like lesions with a reasonable incidence of the defect in the offspring when compared with other models of MMC[16,17,18, 20]. The MMC newborn mice showed evidence of neurological deficits of the hind limbs resulting from an injury that can be ascribed, as it is considered for humans, to an initial error in embryogenesis followed by a secondary extrinsic injury, as stated by the 2-hit hypothesis proposed in previous studies[1, 10, 21].…”

Section: Discussionsupporting

confidence: 70%

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Immunocytochemical Characterization of Astrocytosis along the Spinal Cord of Loop-Tail/Curly-Tail Mice with Myelomeningocele

Reis

Correia‐Pinto²,

Monteiro³

et al. 2008

Pediatr Neurosurg

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Background: The neurological deficits of myelomeningocele (MMC) have been attributed both to a primary neurulation defect and to a secondary injury of the placode in the intrauterine environment. Since astrocytes are involved in glial scar formation after spinal cord injury, the characterization of astrocyte density along the spinal cord upstream of the MMC can be used as a surrogate marker of the extension of the injury beyond the MMC. Methods: The curly-tail/loop-tail murine model was applied to obtain newborn mice with MMC. The astrocyte density and topography both at the MMC placode level and at the upper segments of the spinal cord was characterized by immunolabeling using the anti-glial fibrillary acidic protein antibody. This was followed by a qualitative evaluation of immunolabeled cells and morphometric analysis of the samples. Results: The topography of astrocytes in the spinal cord of MMC newborn mice was compared with that of newborn control mice (without spina bifida aperta) (n = 8/group). The anti-glial fibrillary acidic protein immunoreactivity was significantly increased in the MMC samples in comparison with the normal spinal cord, indicating the presence of an astrocytic response. Increased astrocytosis was also observed in the transitional area located above the MMC. The astrocytosis decreased progressively along the MMC spinal cord until matching the pattern of the control spinal cords. This transitional area involved a segment of the spinal cord with a length of 240 µm in the newborn mouse. Conclusions: MMC newborn mice show spinal cord injury that is located upstream of the exposed placode and is characterized by proliferation of astrocytes. This finding offers further support for the hypothesis of a tethering mechanism as part of the spinal cord injury observed in MMC newborns.

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Section: Discussionsupporting

confidence: 70%

“…Astrogliosis is a common feature of the response of the nervous system tissue to injury as has been documented in studies on spinal cord trauma [14,15,16]. A recent study of ours has documented that there is also a clear enhancement in astrocyte density in the MMC placode [13].…”

Section: Discussionmentioning

confidence: 56%

Immunocytochemical Characterization of Astrocytosis along the Spinal Cord of Loop-Tail/Curly-Tail Mice with Myelomeningocele

Reis

Correia‐Pinto²,

Monteiro³

et al. 2008

Pediatr Neurosurg

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“…in rabbits, Meuli et al 9 in sheep, Pedreira et al 10 in ovine fetuses and Michjeda 11 in non human primates Macaca mulatta; creating intrauterine surgical models to reproduce different diseases and perform its correction. Also George and Fuh 12 , describe the use of non-human primates (Macaca mulatta), as models for the surgical correction of diseases for the neural tube. These have allowed the intrauterine correction of different pathologies in humans, such as myelomeningocele, sacrococcygeal teratoma, obstruction of the urinary tract and lung adenomatoide disease 13,14 .…”

Section: Discussionmentioning

confidence: 99%

Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta)

et al. 2010

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Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta) RESUMO Objetivo:Avaliar o manejo anestésico em cirurgia intra-uterina para induzir mielomeningocelo em primatas não humanos, Macaca mulatta. Métodos: Operaram-se um total de nove fetos in útero que foram submetidos à laminectomia em L5 e L6. As variáveis a estudar foram mortes maternas ou fetais, freqüência cardíaca e respiratória, pressão arterial, temperatura e saturação de oxigênio. Resultados: Não se apresentaram mortes maternas ou fetais, a temperatura se manteve abaixo dos 36°C, não tendo repercussões no bem-estar dos macacos. Conclusão: Não ocorreu nenhum óbito materno ou fetal, sendo que a única variável abaixo do normal foi a temperatura.

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“…27 To better characterize the cytological dynamics in the MMC placode that could lead to neuronal degeneration during gestation, we looked for other cytological alterations not clearly evaluated in previous scientific studies. 10,11,15,17,23 In this way we evaluated the changes in vascular structure, frequency of apoptotic cells, and inflammation in the placode of MMC mutant mouse fetuses during the final stages of gestation.…”

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confidence: 99%

Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

Reis

Correia‐Pinto

Monteiro

et al. 2008

PED

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Object Myelomeningocele (MMC) is a primary neurulation defect that is associated with devastating neurological disabilities in affected newborns. To better characterize the in utero neurodegenerative process of MMC, the authors investigated the changes in vascular organization, apoptosis, and the presence of inflammatory cells during gestation by using a mutant mouse model of MMC. Methods The curly tail/loop tail (ct/lp) mutant mouse model of MMC was chosen to obtain fetuses at different stages of gestation. Mouse fetuses harboring MMC were harvested by caesarean section at embryonic Days 14.5, 16.5, and 18.5 (complete mouse gestation at 19 days, 6 mice/group); littermate fetuses with the same gestational age but without an MMC were used as controls. Samples of the MMC placode or normal spinal cord were stained for immunocytochemical labeling with caveolin antibody (endothelium marker) and activated caspase-3 antibody (apoptosis marker). Samples were morphometrically analyzed with a computer-assisted image analyzer. Results The MMC mice presented with an increase in vascular density from embryonic Days 16.5–18.5 and an enhanced number of apoptotic cells at embryonic Day 18.5, compared with controls. There were scarce signals of an inflammatory reaction in the MMC placode, as a few infiltrating neutrophils were seen only at embryonic Day 18.5. Conclusions Fetal placodes in MMC mice showed evidence of increased vascular density since embryonic Day 16.5 and increased apoptosis at embryonic Day 18.5. These new data support the view that in utero changes of the MMC placode, occurring during the last stages of gestation, contribute to the neuropathological manifestations in full-term newborns with MMC.

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Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for Fetal Surgery

Cited by 17 publications

References 29 publications

Immunocytochemical Characterization of Astrocytosis along the Spinal Cord of Loop-Tail/Curly-Tail Mice with Myelomeningocele

Immunocytochemical Characterization of Astrocytosis along the Spinal Cord of Loop-Tail/Curly-Tail Mice with Myelomeningocele

Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta)

Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

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