title: Intracranial volume changes in craniosynostotic rabbits: effects of age and surgical correction.
abstract: BACKGROUND
  The premature fusion of one or more cranial sutures, termed craniosynostosis, alters normal brain growth patterns and results in compensatory changes in the cranial vault. The authors previously reported that bilateral coronal suture fusion resulted in a reduction in intracranial volume in a rabbit model of nonsyndromic, familial coronal suture synostosis.
  
  
  METHODS
  The current follow-up study involved collecting cross-sectional three-dimensional computed tomographic head scans from 142 rabbits (70 normal, 44 with uncorrected synostosis, and 28 synostosed rabbits with coronal suturectomy) at 0, 10, 25, 42, 84, and 126 days of age. Intracranial contents were reconstructed, and indirect intracranial volume was calculated.
  
  
  RESULTS
  Results revealed a significant (p < 0.05) postsynostotic reduction of intracranial volume (23 percent) by 25 days of age in rabbits with uncorrected craniosynostosis compared with normal controls, which continued through 84 days of age. Also, rabbits with surgically released synostosis, using a simple strip suturectomy, showed significantly (p < 0.05) greater intracranial volume at 25 days of age compared with unoperated synostosed rabbits. However, no changes in intracranial volume were noted between 42 and 84 days of age in rabbits with surgically released synostosis, at which point their intracranial volume was 30 percent less than that in normal control rabbits.
  
  
  CONCLUSIONS
  These data suggest that in rabbits with uncorrected craniosynostosis, compensatory changes in the neurocranium were not capable of compensating for the loss of sutures as growth sites. The results also showed that that surgical release of the synostosed suture improved intracranial volume in the short term (25 to 42 days) but failed to change it in the long term (42 to 84 days), possibly because of rapid resynostosis of the suturectomy site. This study suggests that surgical release of the suture fusion site alone may not be adequate to allow for normal intracranial volume growth in synostotic rabbits. For this reason, it may be efficacious to design and develop adjunct protein and gene therapies to prevent resynostosis and improve postoperative intracranial volume in craniosynostotic individuals.
authors.affiliation: Department of Orthopedic Surgery, The Cleft Palate-Craniofacial Center, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Virender K
authors.initials: VK
authors.lastname: Singhal
authors.forename: Timothy
authors.initials: T
authors.lastname: Barbano
authors.forename: William
authors.initials: W
authors.lastname: Wigginton
authors.forename: Thomas
authors.initials: T
authors.lastname: Rabold
authors.forename: H Wolfgang
authors.initials: HW
authors.lastname: Losken
authors.forename: Michael I
authors.initials: MI
authors.lastname: Siegel
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000254:growth & development; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D002508:Cephalometry; D003393:Cranial Sutures / Q000254:growth & development / Q000473:pathology / Q000601:surgery*; D003398:Craniosynostoses / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics / Q000601:surgery; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D009929:Organ Size; D011817:Rabbits / Q000235:genetics / Q000601:surgery*; D012008:Recurrence; D012886:Skull / Q000000981:diagnostic imaging* / Q000254:growth & development / Q000473:pathology / Q000601:surgery; D014057:Tomography, X-Ray Computed