Morphometric characteristics of anencephalic skulls - A comparative study.

Anencephaly is the most severe form of a neural tube defect resulting from the incomplete occlusion of the anterior neuropore in the fourth week of development and associated with a severely underdeveloped brain mass. As desmal ossification of the neurocranium is induced by the presence of soft tissues (brain), no bone develops as direct consequence of the missing brain. The cranial base, by contrast, is formed by chondral ossification, which is genetically determined, and thus present also in anencephaly. Morphometric characteristics of anencephalic skulls, however, have not yet been investigated in sufficient detail before. In this study we therefore comparatively assessed macroscopic morphological-anatomical and cephalometric CT data on structures and dimensions of 11 macerated anencephalic and 4 normal neonatal skulls highlighting skeletal morphological differences. The most striking results were the missing skullcap and the greatly changed morphology of the existing skull bones, which were reduced in size. The parameters of the skull base, the transverse orbital diameter and maxillary width were significantly smaller in anencephalic skulls. The morphology of the viscerocranium appeared similar to that of normal neonatal skulls. The results of this study can be used in diagnosis and skeletal classification for anencephaly. This can help identify bones that are incomplete, fragmented and taphonomically altered, which is often the case in historical and forensic studies.

Effect of excessive methionine on the development of the cranial growth plate in newborn rats.

OBJECTIVE: Methionine is an essential amino acid and pivotal for normal growth and development. However, previous animal studies have shown that excessive maternal intake of methionine causes growth restrictions, organ damages, and abnormal growth of the mandible in newborn animals. However, the effect of excessive methionine on the development of the cranial growth plate is unknown. This study investigated histological alterations of the cranial growth plate induced by high methionine administration in newborn rats. DESIGN: Twenty pregnant dams were divided into a control and an experimental group. The controls received a diet for rats and the experimental group was fed from the 18th gestational day with a special manufactured high methionine diet for rats. The high methionine diet was maintained until the end of the lactation phase (day 20). The offspring of both groups were killed at day 10 or 20 postnatally and their spheno-occipital synchondroses were collected for histological analysis. RESULTS: The weight of the high-dose methionine treated experimental group was considerably reduced in comparison to the control group at day 10 and 20 postnatally. The cartilaginous area of the growth plate and the height of the proliferative zone were markedly reduced at postnatal day 10 in the experimental group. CONCLUSIONS: In summary, the diet-induced hypermethioninemia in rat dams resulted in growth retardations and histomorphological changes of the spheno-occipital synchondrosis, an important craniofacial growth centre in newborns. This finding may elucidate facial dysmorphoses reported in patients suffering from hypermethioninemia.

Development dependent collagen gene expression in the rat cranial base growth plate.

The spheno-occipital synchondrosis is part of the cranial base growth plate and is of crucial importance in craniofacial development. In this investigation, we studied changes in collagen gene expression in the spheno-occipital synchondrosis in order to identify the developmental stages most important for extracellular matrix production and ossification of the rat cranial base growth plate. Gene transcripts of type II and X collagen were most abundant at day 10 postnatally in the spheno-occipital synchondrosis. This observation is assumed to be due to intrinsic genetic factors and local environmental factors.

The role of apoptosis in early embryonic development of the adenohypophysis in rats.

BACKGROUND: Apoptosis is involved in fundamental processes of life, like embryonic development, tissue homeostasis, or immune defense. Defects in apoptosis cause or contribute to developmental malformation, cancer, and degenerative disorders. METHODS: The developing adenohypophysis area of rat fetuses was studied at the embryonic stage 13.5 (gestational day) for apoptotic and proliferative cell activities using histological serial sections. RESULTS: A high cell proliferation rate was observed throughout the adenohypophysis. In contrast, apoptotic cells visualized by evidence of active caspase-3, were detected only in the basal epithelial cones as an introducing event for fusion and closure of the pharyngeal roof. CONCLUSION: We can clearly show an increasing number of apoptotic events only at the basic fusion sides of the adenohypophysis as well as in the opening region of this organ. Apoptotic destruction of epithelial cells at the basal cones of the adenohypophysis begins even before differentiation of the adenohypophyseal cells and their contact with the neurohypophysis. In early stages of development, thus, apoptotic activity of the adenohypophysis is restricted to the basal areas mentioned. In our test animals, the adenohypophysis develops after closure of the anterior neuroporus.

Growth-related changes of parameters of the methylation cycle and jejunal aminopeptidase M in the rat.

During development from juvenility to adulthood, rats displayed constant vitamin B12, decreasing folic acid and increasing homocysteine levels in blood plasma parallel to decreasing aminopeptidase M activities in the jejunum. The rising homocysteine level with advancing age implies growing metabolic stress and may be seen as cause for the increase of the number of cleft lip alveolus palate at pregnancies in higher age. Similarly, additional morphologic changes of the villi and crypta were regarded to reflect age-related adaptation of the digestive tract. Thus, the rat model is interesting for human-relevant studies of metabolic diseases or fetal anomalies, as in man these parameters develop likewise with increasing age. Sufficient supply of B vitamins is an important factor for a normal course of pregnancy, healthy offsprings and physiologic blood parameters and is essential to a stable methylation cycle.

Induction and prevention of cleft lip, alveolus and palate and neural tube defects with special consideration of B vitamins and the methylation cycle.

Previous studies on the development of cleft lip, alveolus, palate, and velum and neural tube defects have revealed several shared multifactorial causes. Both anomalies emerge at different times during embryonic development and are not associated with each other unless there is a genetic component to the etiology. Vitamin deficiency disorders are one of several factors contributing to the etiology of these anomalies.Vitamins B6, folic acid and B12 play an essential role in the methylation cycle. A lack of or deficiency in these vitamins thus has severe consequences for the organism, especially the unborn child. Due to its short half-life, vitamin B6 is particularly important for undisturbed embryogenesis and should be taken along with folic acid as a periconceptional supplement to prevent embryonic deformities. This paper is intended to provide the orthodontist (as a member of the interdisciplinary cleft team) with an overview of the issues and etiological significance of vitamin B deficiencies as possible inducers of these embryopathies. This may encourage comprehensive counselling, particularly of parents of children born with deformities who wish to have more children.

Secondary palatal closure in rats in association with relative maternofetal levels of folic acid, vitamin B12, and homocysteine.

Animal experiments are used in embryological and teratological studies of matters relevant to humans. In gravid rats, a decrease in the levels of folic acid and vitamin B12 was observed in maternal blood and in amniotic fluid. At the time of secondary palatal closure (14th day of pregnancy), the folic acid level of the amniotic fluid was 73% lower than that of the maternal blood. A drop in vitamin B12 in conjunction with an increase in amniotic homocysteine levels is seen as a risk factor for malformation of the palate. The understanding of causes of cleft generation could lead to a prophylactic treatment approach.

Morphofunctional changes of orofacial muscles in patients with unilateral or bilateral cleft lip, alveolus and palate.

The facial musculature is part of a biocybernetic feedback system within the stomatognathic system, the continuity of which is disturbed by clefts of the lip, jaw, and palate (cheilognathopalatoschisis). This results in topographic, fine-structural and functional alterations of the facial musculature. In two heads with unilateral clefts and two heads with bilateral clefts, the facial musculature was dissected and the M. orbicularis oris macroscopically and topographically examined. We found changes in the attachment of the M. orbicularis oris. The modiolus, which is coresponsible for the proper topographic relation of the M. obicularis oris to the other facial muscles, was unchanged. Further, we examined the vascular system of the muscle, which likewise adapts to the altered situation. Lip/jaw/palatal clefts result in anatomically functional and fine-structural alterations of the M. orbicularis oris, while the rest of the facial musculature remains unchanged.

Regional changes in the masseter muscle of rats after reduction of blood supply.

The masticatory musculature is an integral functional part of the stomatognathic system and influences craniofacial morphogenesis and morphology. This animal study aimed to investigate the morphological consequences of restricted regional blood supply to the m. masseter. A total of 20 adult male Wistar rats (Rattus norvegicus Berkenhout) were divided into an experimental group and a control group comprised of 10 animals respectively and kept under standardized conditions. The experimental group underwent a dextrolateral complete surgical ligation of the a. carotis communis and, after 5 weeks, specimens were taken from the masseters. The muscle samples were analyzed immunohistochemically for fiber distribution and capillary density. Analysis revealed a discrete increase in the proportion of type I fibers with a significant increase of capillary number per area. Although no agreement exists on the alterations occurring in chronically ischemic muscles, it may be assumed that chronic ischemia evokes histomorphological adaptation processes similar to endurance training effects.

Functional 3-D analysis of patients with unilateral cleft of lip, alveolus and palate (UCLAP) following lip repair.

INTRODUCTION: Particular importance is attached to lip repair cleft surgery, as numerous functional and aesthetic aspects have to be taken into account simultaneously. Spatial assessment of function and depiction of dynamic deviations is reasonable for describing surgical outcome in addition to long standing static analysis. This study aimed at 3D analysis of the oral area after reconstruction in patients with unilateral cleft lip, alveolus and palate. PATIENTS AND METHODS: Twelve patients with unilateral cleft lip, alveolus and palate who underwent surgery according to Tennison-Randall were enrolled in this study. Soft tissue dynamics was analysed during passive stretching and active contraction of the lips, and photogrammetry was used for comparing relative changes of length and displacement vectors. The spatial coordinates of surgically significant and reproducible landmarks along the red-white lip junction were analyzed. RESULTS: Static analysis of the lips revealed a good result with far-reaching symmetry in all cases. Regarding dynamic behaviour, two groups could be distinguished showing clear differences of passive distension and contraction behaviour. CONCLUSION: Despite nominally identical surgical techniques and comparable static-morphological outcomes, dynamic analysis revealed differences pointing to a need for optimization.

Histological and histomorphometric study of growth-related changes of cranial sutures in the animal model.

INTRODUCTION: During the early development, numerous histological and morphometric changes occur in the cranial sutures the exact knowledge of which is of fundamental significance for understanding clinically relevant cranial anomalies. In this paper a histological and histomorphometric longitudinal study of the coronal, sagittal and lambdoid sutures in the rat is reported in relation to age. MATERIAL AND METHODS: Forty-eight male Wistar rats (Rattus norvegicus Berkenhout) were raised under standard conditions. Eight animals each were sacrificed at defined time points (10, 14, 28, 42, 70, 98 days post partum) for specimen preparation. Histological preparations of the sagittal, coronal and lambdoid sutures were produced and examined morphologically and histomorphometrically (suture width, height, and area). RESULTS: Histologically, three phases of sutural growth with characteristic structural features were found. Histomorphometry reveals a quasi linear increase in height from the 30th to the 98th day post partum. Suture width remained relatively constant in the area of dura mater and periosteum. CONCLUSION: The sutures of the test animals studied had a similar growth behaviour primarily consisting of an increase in height with almost constant width. The three-phases of development could be demonstrated histologically in all sutures.