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Erschienen in: Pediatric Surgery International 12/2008

01.12.2008 | Original Article

Brain malformations in the sheep model of myelomeningocele are similar to those found in human disease: preliminary report

verfasst von: Jose Luis Encinas Hernández, C. Soto, M. A. García-Cabezas, F. Pederiva, M. Garriboli, R. Rodríguez, J. L. Peiró, F. Carceller, M. López-Santamaría, J. A. Tovar

Erschienen in: Pediatric Surgery International | Ausgabe 12/2008

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Abstract

Purpose

To examine if brain malformations, similar to those which account for cognitive disorders seen in human disease, are present in an ovine model of myelomeningocele (MMC).

Methods

An MMC-like lesion was surgically created in 16 fetal lambs between 60 and 80 days of gestation. Ten did not undergo fetal repair (group A), 2 were repaired with an open two-layer closure (group B), 2 with open bioglue coverage (group C) and 2 with fetoscopic coverage (group D). Lambs were killed and their brains were examined. Two brains from normal unoperated lambs served as controls.

Results

Thirteen lambs died in utero (81%). Two lambs in group A and 1 in group B were delivered at term. Group A brains showed hydrocephalus and extensive areas of polymicrogyria. There was also an extensive denudation of the ependymal lining under the polymicrogyric areas and the corpus callosum was thinner than normal. No hindbrain herniation was observed. Brains from group B and the control did not show any of these abnormalities.

Conclusions

Some of the central nervous system abnormalities associated to MMC in human patients are also found in the uncorrected fetal lamb model of MMC but not in the only survivor to intrauterine coverage. Further studies are necessary to ascertain if these abnormalities can be prevented by coverage of the defect.
Literatur
1.
Zurück zum Zitat Grosfeld JL, O′Neill JA, Fonkalsrud EW, Coran AG (2006) Pediatric surgery. Elsevier, Mosby, pp 1987–2002 Grosfeld JL, O′Neill JA, Fonkalsrud EW, Coran AG (2006) Pediatric surgery. Elsevier, Mosby, pp 1987–2002
2.
Zurück zum Zitat Hutchins GM, Meuli M, Meuli-Simmen C, Jordan MA, Heffez DS, Blakemore KJ (1996) Acquired spinal cord injury in human fetuses with myelomeningocele. Pediatr Path Lab Med 16:701–702CrossRef Hutchins GM, Meuli M, Meuli-Simmen C, Jordan MA, Heffez DS, Blakemore KJ (1996) Acquired spinal cord injury in human fetuses with myelomeningocele. Pediatr Path Lab Med 16:701–702CrossRef
3.
Zurück zum Zitat Juliá V, Sancho M, Albert A, Conill J, Martínez A, Grande C, Morales L (2006) Prenatal covering of the spinal cord decreases neurologic sequelae in a myelomeningocele model. J Pediatr Surg 41:1125–1129PubMedCrossRef Juliá V, Sancho M, Albert A, Conill J, Martínez A, Grande C, Morales L (2006) Prenatal covering of the spinal cord decreases neurologic sequelae in a myelomeningocele model. J Pediatr Surg 41:1125–1129PubMedCrossRef
4.
Zurück zum Zitat Tulipan N, Hernanz-Schulman M, Bruner JP (1998) Reduced hindbrain herniation after intrauterine myelomeningocele repair, a report of four cases. Pediatr Neurosurg 29:274–278PubMedCrossRef Tulipan N, Hernanz-Schulman M, Bruner JP (1998) Reduced hindbrain herniation after intrauterine myelomeningocele repair, a report of four cases. Pediatr Neurosurg 29:274–278PubMedCrossRef
5.
Zurück zum Zitat Bruner JP, Tulipan L, Paschall RL (1999) Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. JAMA 282:1819–1825PubMedCrossRef Bruner JP, Tulipan L, Paschall RL (1999) Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. JAMA 282:1819–1825PubMedCrossRef
6.
Zurück zum Zitat Heffez DS, Aryanpur J, Hutchins GM (1990) The paralysis associated with myelomeningocele. Experimental data implicating a preventable spinal cord injury. Neurosurg 26:987–992CrossRef Heffez DS, Aryanpur J, Hutchins GM (1990) The paralysis associated with myelomeningocele. Experimental data implicating a preventable spinal cord injury. Neurosurg 26:987–992CrossRef
7.
Zurück zum Zitat Jonnson M, Gerdes M, Rintoul N, Pasquariello P, Melchionni J, Sutton L, Adzick S (2006) Maternal-fetal surgery for myelomeningocele: neurodevelopmental outcomes at 2 years of age. Am J Obs Gynecol 194:1145–1152CrossRef Jonnson M, Gerdes M, Rintoul N, Pasquariello P, Melchionni J, Sutton L, Adzick S (2006) Maternal-fetal surgery for myelomeningocele: neurodevelopmental outcomes at 2 years of age. Am J Obs Gynecol 194:1145–1152CrossRef
8.
Zurück zum Zitat Difederico EM, Burlingame JM, Kilptrick SJ, Harrison MR, Mattay MA (1998) Pulmonary edema in obstetric patiens rapidly resolved except in the presence of infectión or of nitroglycerin tocolysis after open fetal surgery. Am J Obstet Gynecol 179:925–933PubMedCrossRef Difederico EM, Burlingame JM, Kilptrick SJ, Harrison MR, Mattay MA (1998) Pulmonary edema in obstetric patiens rapidly resolved except in the presence of infectión or of nitroglycerin tocolysis after open fetal surgery. Am J Obstet Gynecol 179:925–933PubMedCrossRef
9.
Zurück zum Zitat Longaker MT, Gobus MS, Filly RA, Rosen MA, Chang SW, Harrison MR (1991) Maternal outcome after fetal surgery. JAMA 265:737–741PubMedCrossRef Longaker MT, Gobus MS, Filly RA, Rosen MA, Chang SW, Harrison MR (1991) Maternal outcome after fetal surgery. JAMA 265:737–741PubMedCrossRef
10.
Zurück zum Zitat DiFiderico EM, Harrison MR, Matthay MA (1996) Pulmonary edema in a woman following fetal surgery. Chest 109:1114–1117CrossRef DiFiderico EM, Harrison MR, Matthay MA (1996) Pulmonary edema in a woman following fetal surgery. Chest 109:1114–1117CrossRef
11.
Zurück zum Zitat Bruner JP, Richar WO, Tulipan NB, Arney TL (1999) Endoscopic coverage of myelomeningocele in utero. Am J Obstet Gynecol 180:153–158PubMedCrossRef Bruner JP, Richar WO, Tulipan NB, Arney TL (1999) Endoscopic coverage of myelomeningocele in utero. Am J Obstet Gynecol 180:153–158PubMedCrossRef
12.
Zurück zum Zitat Kohl T, Hartlage MG, Kiehitz D, Westphal M, Buller T, Achenbach S, Aryee S, Gembruch U, Brentrup A (2003) Percuteous fetoscopic patch coverage of experimental lumbosacral full-thickness skin lesions in sheep. Surg Endoscop 23:24–28 Kohl T, Hartlage MG, Kiehitz D, Westphal M, Buller T, Achenbach S, Aryee S, Gembruch U, Brentrup A (2003) Percuteous fetoscopic patch coverage of experimental lumbosacral full-thickness skin lesions in sheep. Surg Endoscop 23:24–28
13.
Zurück zum Zitat Bruner JP, Tulipan NB, Richards WO, Walsh WF, Boehm FH, Vrabcak EK (2000) In utero repair of myelomeningocele: a comparison of endoscopy and hysterotomy. Fetal Diagn Ther 15:83–88PubMedCrossRef Bruner JP, Tulipan NB, Richards WO, Walsh WF, Boehm FH, Vrabcak EK (2000) In utero repair of myelomeningocele: a comparison of endoscopy and hysterotomy. Fetal Diagn Ther 15:83–88PubMedCrossRef
14.
Zurück zum Zitat Maureen D, Edelstein K, Hetherington R, Copeland K, Frederick J, Blaser S, Kramer L, Drake J, Brandt M, Fletcher J (2004) Neurobiology of perceptual and motor timing in children with spina bifida in relation to cerebellar volume. Brain 127:1292–1301CrossRef Maureen D, Edelstein K, Hetherington R, Copeland K, Frederick J, Blaser S, Kramer L, Drake J, Brandt M, Fletcher J (2004) Neurobiology of perceptual and motor timing in children with spina bifida in relation to cerebellar volume. Brain 127:1292–1301CrossRef
15.
Zurück zum Zitat Haynes R, Borestein N, Desilva T, Folkerth R, Lena L, Volpe J, Kinney H (2005) Axonal development in the cerebral white matter of the human fetus and infant. J Comp Neurol 484:156–167PubMedCrossRef Haynes R, Borestein N, Desilva T, Folkerth R, Lena L, Volpe J, Kinney H (2005) Axonal development in the cerebral white matter of the human fetus and infant. J Comp Neurol 484:156–167PubMedCrossRef
16.
Zurück zum Zitat Shim I, Yoon Ha, Young J, Lee HJ, Yang K, Chang J (2003) Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus. Neurosurg 53:416–424CrossRef Shim I, Yoon Ha, Young J, Lee HJ, Yang K, Chang J (2003) Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus. Neurosurg 53:416–424CrossRef
17.
Zurück zum Zitat da Silva L, Rubens H, Lachat JJ (2003) Study of corpus callosum in experimental hydrocephalic wistar rats. Acta Cir Bras 18:10–14CrossRef da Silva L, Rubens H, Lachat JJ (2003) Study of corpus callosum in experimental hydrocephalic wistar rats. Acta Cir Bras 18:10–14CrossRef
18.
Zurück zum Zitat Hale P, McAllister J, Katz S, Wright LC, Lovely T, Miller D (1992) Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement. Neurosurg 31:1085–1096CrossRef Hale P, McAllister J, Katz S, Wright LC, Lovely T, Miller D (1992) Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement. Neurosurg 31:1085–1096CrossRef
19.
Zurück zum Zitat Yingling C, Meuli-Simmen C, Meuli M, Timel G, Harrison M, Adzick S (1999) Experimental fetal neurosurgery: effects of in-utero manipulations of somatosensory evoked potentials. Ped Surg Int 15:535–539CrossRef Yingling C, Meuli-Simmen C, Meuli M, Timel G, Harrison M, Adzick S (1999) Experimental fetal neurosurgery: effects of in-utero manipulations of somatosensory evoked potentials. Ped Surg Int 15:535–539CrossRef
20.
Zurück zum Zitat Jennigs RW, Wilkinson C, Westerberg B (2006) Chari malformation develops in surgically created myelomeningocele and its prevented by repair of the myelomeningocele in fetal lambs. Am J Obstet Gynecol 41:11–13 Jennigs RW, Wilkinson C, Westerberg B (2006) Chari malformation develops in surgically created myelomeningocele and its prevented by repair of the myelomeningocele in fetal lambs. Am J Obstet Gynecol 41:11–13
21.
Zurück zum Zitat Meuli A, Simmen C, Hutchins GM (1995) In utero surgery neurologic function at birth in sheep with spina bifida. J Pediatr Surg 30:342–347 Meuli A, Simmen C, Hutchins GM (1995) In utero surgery neurologic function at birth in sheep with spina bifida. J Pediatr Surg 30:342–347
22.
Zurück zum Zitat Meuli M, Meuli-Simmen C, Yingling CD, Hutchins GM, Seller M, Harrison MR, Adkizt M (1995) Creation of myelomeningocele in utero. A model of functional damage from spinal cord: exposure in fetal sheep. J Pediatr Surg 30:1028–1032PubMedCrossRef Meuli M, Meuli-Simmen C, Yingling CD, Hutchins GM, Seller M, Harrison MR, Adkizt M (1995) Creation of myelomeningocele in utero. A model of functional damage from spinal cord: exposure in fetal sheep. J Pediatr Surg 30:1028–1032PubMedCrossRef
23.
Zurück zum Zitat McLone DG (1989) The cause of Chiari II malformation: a unified theory. Pediatr Neurocsci 15:1–12CrossRef McLone DG (1989) The cause of Chiari II malformation: a unified theory. Pediatr Neurocsci 15:1–12CrossRef
24.
Zurück zum Zitat de Wit O, den Dunnen W, Sollie K, Iris R, Meiners L, Brouwer O, Rodriguez E, Silval D (2008) Pathogenesis of cerebral malformations in human fetues with myelomeningocele. Cerebrospinal Fluid Res 5:4PubMedCrossRef de Wit O, den Dunnen W, Sollie K, Iris R, Meiners L, Brouwer O, Rodriguez E, Silval D (2008) Pathogenesis of cerebral malformations in human fetues with myelomeningocele. Cerebrospinal Fluid Res 5:4PubMedCrossRef
25.
Zurück zum Zitat Jimenez AJ, Tome M, Wagner C, Rodriguez S, Fernández-Llebrez P, Rodriguez EM, Pérez-Figares JM (2001) A programmed ependimal denudation precedes congenital hydrocephalus in the hyh mutant mouse. J Neuropathol Exp Neurol 60:1105–1119PubMed Jimenez AJ, Tome M, Wagner C, Rodriguez S, Fernández-Llebrez P, Rodriguez EM, Pérez-Figares JM (2001) A programmed ependimal denudation precedes congenital hydrocephalus in the hyh mutant mouse. J Neuropathol Exp Neurol 60:1105–1119PubMed
26.
Zurück zum Zitat Golden JA, Hardin BN (2004) Pathology and genetic developmental neuropathology. Neuropahty Press, Baser Golden JA, Hardin BN (2004) Pathology and genetic developmental neuropathology. Neuropahty Press, Baser
27.
Zurück zum Zitat Lawson RF, Raimondi AJ (1973) Hydrocephalus-3, a murine mutant. Alterations in fine structure of choroid plexus and ependyma. Surg Neurol 1:115–128PubMed Lawson RF, Raimondi AJ (1973) Hydrocephalus-3, a murine mutant. Alterations in fine structure of choroid plexus and ependyma. Surg Neurol 1:115–128PubMed
28.
Zurück zum Zitat Page RB, Leure-duPree AE (1983) Ependymal alterations in hydrocephalus. Neur Cer Fluid 43:789–820 Page RB, Leure-duPree AE (1983) Ependymal alterations in hydrocephalus. Neur Cer Fluid 43:789–820
29.
30.
Zurück zum Zitat Rodriguez EM (1976) The cerebrospinal fluid as a pathway in neuroendocrine integration. Review. J Endocrinol 71:407–443PubMedCrossRef Rodriguez EM (1976) The cerebrospinal fluid as a pathway in neuroendocrine integration. Review. J Endocrinol 71:407–443PubMedCrossRef
31.
Zurück zum Zitat Humphreis P, Muzumdar D, Ll Sly, Michaud D (2007) Focal cerebral mantle disruption in fetal hydrocephalus. Pediatr Neurol 36:236–243CrossRef Humphreis P, Muzumdar D, Ll Sly, Michaud D (2007) Focal cerebral mantle disruption in fetal hydrocephalus. Pediatr Neurol 36:236–243CrossRef
32.
Zurück zum Zitat Paek BW, Farmer DL, Wilkinson CC, Albanese CT, Peakock W, Harrison MR (2000) Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs. Am J Obstet Gynecol 183:1119–1123PubMedCrossRef Paek BW, Farmer DL, Wilkinson CC, Albanese CT, Peakock W, Harrison MR (2000) Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs. Am J Obstet Gynecol 183:1119–1123PubMedCrossRef
33.
Zurück zum Zitat Bouchard S, Davey MG, Rintoul NE, Walsh DS, Rorke LB, Adzick NS (2003) Correction of hindbrain herniation and anatomy of the vermis after in utero repair of mielomeningocele in sheep. J Pediatr Surg 38:451–458PubMedCrossRef Bouchard S, Davey MG, Rintoul NE, Walsh DS, Rorke LB, Adzick NS (2003) Correction of hindbrain herniation and anatomy of the vermis after in utero repair of mielomeningocele in sheep. J Pediatr Surg 38:451–458PubMedCrossRef
34.
Zurück zum Zitat von Koch C, Compagnone N, Shinjiro H, Suzzane Y, Harrison M, Farmer D (2005) Myelomeningocele: characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease. Am J Obst Gynecol 193:1456–1462CrossRef von Koch C, Compagnone N, Shinjiro H, Suzzane Y, Harrison M, Farmer D (2005) Myelomeningocele: characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease. Am J Obst Gynecol 193:1456–1462CrossRef
35.
Zurück zum Zitat Juranek J, Fletcher J, Hasan K, Breier J, Cirino P, Pazo-Alvarez P, Diaz J, Ewing-Cobbs E, Dennis M, Papanicolau A (2008) Neocortical organization in spina bifida. Neuroimage 40:1516–1522PubMedCrossRef Juranek J, Fletcher J, Hasan K, Breier J, Cirino P, Pazo-Alvarez P, Diaz J, Ewing-Cobbs E, Dennis M, Papanicolau A (2008) Neocortical organization in spina bifida. Neuroimage 40:1516–1522PubMedCrossRef
Metadaten
Titel
Brain malformations in the sheep model of myelomeningocele are similar to those found in human disease: preliminary report
verfasst von
Jose Luis Encinas Hernández
C. Soto
M. A. García-Cabezas
F. Pederiva
M. Garriboli
R. Rodríguez
J. L. Peiró
F. Carceller
M. López-Santamaría
J. A. Tovar
Publikationsdatum
01.12.2008
Verlag
Springer-Verlag
Erschienen in
Pediatric Surgery International / Ausgabe 12/2008
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-008-2276-8

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