A morphometric, neuroanatomical, and behavioral study on the effects of geometric constraint on the growing brain: The methyl 2-cyanoacrylate craniosynostosis model

Object. The effects of premature sutural synostosis on the developing brain remain unknown. A model of craniosynostosis in the perinatal rat was used to investigate the morphological and cytoarchitectural changes in the maturing brain as well as the neurobehavioral outcome. Methods. A total of 56 perinatal rats, eight in each subgroup, were used in this study. Hypothermic arrest was induced in the rats and methyl 2-cyanocrylate was applied across the sagittal, coronal, and lambdoidal sutures at postnatal Days 0, 3, and 7. Sham rats underwent similar hypothermic arrest and application of methyl 2-cyanoacrylate but at a site different from the sutural lines. Age-matched rats that did not undergo any procedure were included as normal controls. Serial gross measurements were obtained to chart calvarial growth and computerized tomography scanning was performed to calculate mean calvarial volumes. At postnatal Day 30, the brains were fixed in situ and detailed morphological and cytoarchitectural analysis was conducted. There were no statistical differences in any of the analyses between sham rats and normal age-matched controls. In contrast, calvarial growth rates (analysis of variance, p < 0.05), mean brain weights (t-test, p < 0.01), and anterior-posterior and lateral diameter measurements (t-test, p < 0.01) were different for all synostotic rats compared with sham controls. On cytoarchitectural surveys, focal areas of nodular heterotopia and differences in cell density at the pyramidal cell layer were noted (t-test, p < 0.01). Open field testing also demonstrated excessive exploratory behavior in the synostosed animals. Conclusions. Early pan-calvarial sutural synostosis in the perinatal rat after administration of methyl 2-cyanoacrylate is associated with morphometrical and cytoarchitectural changes in the developing brain.