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Biomedical subjects

A M Burrows

Publications and source records attributed to A M Burrows.

At least 19 recordsLinked to original sources

Comparison of hind limb muscle mass in neonate and adult prosimian primates.

Little ontogenetic data exist to indicate whether muscular organization of neonates reflects adult locomotion (e.g., leaping) or infant activities like clinging or the initial quadrupedal phase of locomotion that typifies most infant primates. In the present study, five species of primates with contrasting modes of locomotion were examined. Twenty-eight preserved neonatal and adult cadavers were studied by careful dissection of the hip, thigh, and leg muscles. Wet weights were taken of limb muscles after removal, and the muscles were combined into major functional groups (e.g., flexors, extensors) of each limb segment. Results demonstrate that the distribution of muscle mass within the thigh and within the leg are similar between neonates and adults for all species, with major groups varying by 5% or less in all but two age comparisons. Crural indices of the neonates are nearly identical to those of the adults, but leg/thigh muscle mass ratios were higher in the neonates. Species vary greatly in the percentage of adult limb segment muscle mass present in neonates, with Tarsius syrichta having the greatest percentage for all segments and two lemurids showing the least. These results primarily track differences in relative body mass at birth rather than developmental differences. The adaptive distribution of muscle, as discussed previously for adult prosimians, appears to be established at birth. Neonates of leaping species already have much larger quadriceps muscles than quadrupeds. Differences between large- and small-bodied leapers (e.g., pronounced superficial plantarflexor masses in tarsiers and pronounced deep plantarflexor masses in sifakas) also are present in neonates. Ratios of muscle mass over body mass are smaller in all neonates than in their adult counterparts, suggesting that the neonates are relatively poorly muscled, and that muscle mass must increase with positive allometry during growth.

Aging↗

Cranial base changes following coronal suturectomy in craniosynostotic rabbits.

It has been suggested that surgical release of synostosed sutures may ameliorate various cranial base abnormalities in craniosynostotic patients. The present study was designed to test this hypothesis in a rabbit model with familial coronal suture synostosis (CSS). Data were collected from 56 New Zealand White rabbits: 32 unaffected controls, 11 with unoperated CSS, and 13 with CSS released by suturectomy performed at 25 days of age. Serial radiographs were taken at 25, 42 and 84 days. Linear, angular and triangular shape cranial base measurements were compared using ANOVA and tensor biometric analysis. Results revealed that at 84 days, both groups of CSS rabbits had significantly (p < 0.05) different anterior and total cranial base lengths, flatter cranial base angles, and dysmorphic anterior cranial base shapes when compared with normals. Significant (p < 0.05) differences were noted only for palatal and cranial base angles and posterior cranial base shape between CSS rabbits with and without suturectomy. However, significant (p < 0.05) changes were noted between pre- and postoperative measurements in posterior and total cranial base lengths and anterior and posterior cranial base shapes in CSS rabbits with suturectomy. Results revealed that surgical release of synostosed coronal sutures through suturectomy did not normalize cranial base growth patterns in CSS rabbits. These findings may be explained by the relatively late age of surgical release or suturectomy site resynostosis with continued dysmorphic cranial base growth. Alternatively, cranial base abnormalities seen in CSS rabbits may be early primary malformations, not secondary deformations amenable to surgical modification.

Analysis of Variance↗

Anatomical position of the vomeronasal organ in postnatal humans.

In the last decade or so, there has been a renewed interest in the adult human vomeronasal organ (VNO). Studies have yielded sometimes disparate findings about the microscopic structure of the organ and its supporting tissues. Such varied descriptions may be due to examination of different regions of the VNO, individual variation of VNOs among humans, or the presence of multiple, non-homologous structures that bear false resemblance to the human VNO. A histological description of the spatial relationship of the human VNO to other nasal septal elements is needed to ensure that all investigators are examining the same regions and homologous structures. Histologically sectioned nasal septa from, 22 human cadavers (1 child, 21 adults) were examined grossly and by light microscopy for the VNO. Using histological sections, the position of the VNO relative to other structures was estimated. Sections containing the VNO were retrospectively compared to scaled photographic slides of the unsectioned septa to identify surface landmarks. Human VNOs varied in anteroposterior and superoinferior position relative to the anterior nasal spine and the nasal cavity floor. In the absence of a visible duct opening, the only reliable surface marker, no consistent surface markings were noted for precise location. VNOs were frequently found superior to swellings associated with the paraseptal and/or septal cartilages. Such findings demonstrate that the human VNO is positionally variable, which may have contributed to previous conflicting findings on presence versus absence. Furthermore, our findings support recent suggestions that the VNO may have been misidentified by some investigators, and that its opening can be easily confused with other structures.

Adult↗

The existence of the vomeronasal organ in postnatal chimpanzees and evidence for its homology with that of humans.

It is currently thought that New World monkeys, prosimians, and humans are the only primates to possess vomeronasal organs (VNOs) as adults. Recent studies of the human VNO suggest that previous investigations on Old World primates may have missed the VNO. We examined nasal septa from the chimpanzee (Pan troglodytes) grossly and histologically for comparison with nasal septa from humans, Old World monkeys (Macaca fascicularis, M. nemistrina) and prosimian primates (Microcebus murinus, Otolemur garnettii). Grossly, chimpanzees had depressions on the nasal septum similar to fossae reported anterior to the VNO openings in humans. Histologically, chimpanzees and humans had bilateral epithelial tubes which were above the superior margin of the paraseptal cartilages (vomeronasal cartilage homologue). The epithelial tubes had a homogeneous ciliated epithelium. These structures were thus positionally and structurally identical to the human VNO and unlike the well-developed prosimian VNOs which were surrounded by vomeronasal cartilage. Macaques had no structures which resembled the VNO of either the prosimians or humans. The results demonstrate that the VNO is present postnatally in the chimpanzee and is almost identical to the human VNO in its anatomical position and histological structure. This in turn suggests that the reported absence of the VNO in at least some adult Old World primates is artifactual, and that further study may provide evidence for its existence in other species.

Adult↗

Correction of coronal suture synostosis using suture and dura mater allografts in rabbits with familial craniosynostosis.

OBJECTIVE: Resynostosis following surgical correction of craniosynostosis is a common clinical correlate. Recent studies suggest that the dura mater is necessary to maintain suture patency. It has also been hypothesized that dura mater from synostotic individuals may provide aberrant biochemical signals to the osteogenic fronts of the calvaria, which result in premature suture fusion and subsequent resynostosis following surgery. This study was designed to test this hypothesis by surgically manipulating the coronal suture and dura mater in rabbits with familial craniosynostosis to prevent postsurgical resynostosis. DESIGN: Craniofacial growth and histomorphometric data were collected from 129 rabbits: 72 normal controls and 57 rabbits with bilateral coronal suture synostosis (15 unoperated on controls; 13 surgical controls; 9 dura mater transplant only; 10 suture transplant only; and 10 suture and dura mater transplant). At 10 days of age, all rabbits had radiopaque amalgam markers placed on either side of the coronal, frontonasal, and anterior lambdoidal sutures. At 25 days of age, 42 synostosed rabbits had a 3 to 5-mm wide coronal suturectomy. Coronal sutures and/or underlying dura mater allografts were harvested from same-aged, wild-type, isohistogenic control rabbits and transplanted onto the dura mater of synostosed host rabbits. Serial radiographs were taken at 10, 25, 42, and 84 days of age, and the suturectomy sites were harvested at 84 days of age in 44 rabbits and serially sectioned for histomorphometric examination. RESULTS: Results revealed that cranial vault growth was significantly (p < .05) improved following surgical release of the fused coronal suture compared with synostosed rabbits who were not operated on but was still significantly different (p < .05) from that of normal control rabbits. By 84 days of age, significant (p < .05) differences were noted in calvarial suture marker separation, cranial vault shape indices, and cranial base angles between rabbits with and without dura mater allografts, probably as a result of resynostosis of the suturectomy site or suture-only allografts. Qualitative histological examination revealed that at 84 days of age rabbits with suture and dura allografts had patent coronal sutures, suture-only allografts had fused coronal sutures with extensive endosteal hyperostosis, dura mater-only allografts had some new bone in the suturectomy site that resembled rudimentary osteogenic fronts, and suturectomy controls had extensive endosteal bone formation and resynostosis of the suturectomy site. Significantly (p < .05) more bone was found in the suturectomy sites of rabbits without dura mater allografts compared with rabbits with dura mater allografts. CONCLUSIONS: Results support the initial hypothesis that normal dura mater allografts will maintain suture or suturectomy site patency and allow unrestricted craniofacial growth. However, it is still unclear whether the dura mater from normal rabbits was providing biochemical signals to the transplanted sutures or suturectomy sites or simply acting as a barrier to prevent abnormal biochemical signals from the dura mater of synostosed rabbits from reaching the calvaria. The clinical and therapeutic implications of these procedures are discussed.

Analysis of Variance↗

Endocranial vascular patterns in a familial rabbit model of coronal suture synostosis.

OBJECTIVE: The present study investigates the potential relationship between craniosynostosis and any changes in endocranial vasculature. The hypothesis that crania from rabbits with familial, nonsyndromic coronal suture synostosis and crania from rabbits with experimental immobilization of the coronal suture are associated with altered form of the middle meningeal vessels and dural venous sinuses is tested. DESIGN: Silicone rubber endocasts from 14 adult New Zealand white rabbits (Oryctolagus cuniculus) with familial nonsyndromic coronal suture synostosis (five with bilateral coronal suture synostosis and nine with unilateral coronal suture synostosis) were made to assess middle meningeal vessel and dural venous sinus form. For comparative purposes, endocasts were made from 25 rabbits with normal, patent coronal sutures and 10 rabbits with experimental immobilization of the coronal suture. Impressions of the dural venous sinuses were assessed for depth and width. The area of the confluens of sinuses was also assessed. Impressions of the middle meningeal vessels were assessed for depth, width, and degree of convolution. For width of the dural venous sinuses and area of the confluens of sinuses, comparisons among groups were made with a one-way analysis of variance (ANOVA). For depth of the dural venous sinuses and impressions of the middle meningeal vessels, comparisons among groups were made using a Kruskal-Wallis one-way ANOVA. RESULTS: Crania with familial coronal suture synostosis had significantly (p <.05) reduced posterior dural venous sinus dimensions when compared with both crania from rabbits with experimental immobilization of the coronal suture and rabbits with normal coronal sutures. Crania with both coronal suture synostosis and experimental immobilization had significant increases in dimensions of the middle meningeal vessels relative to normal crania. In addition, casts from rabbits with unicoronal suture synostosis showed marked asymmetry in the dural venous sinuses. CONCLUSIONS: These results support the hypothesis that craniosynostosis is associated with alterations in endocranial vasculature. These changes are most likely a secondary response to synostosis rather than a causal factor and may reflect increased intracranial pressure, decreased intracranial volume, and local accumulations and reductions of cerebrospinal fluid in the posterior region of the skull and immediately deep to the coronal suture.

Analysis of Variance↗

Trigonocephaly in rabbits with familial interfrontal suture synostosis: the multiple effects of premature single-suture fusion.

Previous studies from our laboratory have characterized the craniofacial morphology and growth patterns of an inbred strain of rabbits with autosomal dominant coronal suture synostosis. A number of rabbit perinates from this colony have been collected sporadically over a 5-year period with premature interfrontal suture synostosis. The present study describes the very early onset of craniofacial dysmorphology of these rabbits and compares them to similar-aged normal control rabbits. A total of 40 perinatal New Zealand White rabbits were used in the present study. Twenty-one comprised the sample with interfrontal suture synostosis and ranged in age from 27 to 38 days postconception (term = 31 days) with a mean age of 33.53 days (+/-2.84 days). Nineteen rabbits served as age-matched, normal controls (mean age = 33.05 days +/-2.79 days). Lateral and dorsoventral radiographs were collected from each rabbit. The radiographs were traced, computer digitized, and 12 craniofacial measurements, angles, and indices were obtained. Mean measures were compared using an unpaired Student's t-test. All synostosed rabbits were stillborn or died shortly after birth. Grossly, these rabbits exhibited extreme frontal bossing, trigonocephaly with sagittal keeling, and midfacial shortening. No somatic anomalies were noted. Radiographically, rabbits with interfrontal suture synostosis had significantly (P < 0.05) narrower bifrontal widths, shorter cranial vault lengths, kyphotic cranial base angles, and different cranial vault indices (shapes) compared to controls. Results reveal severe and early pathological and compensatory cranial vault changes associated with premature interfrontal suture synostosis in this rabbit model. The 100% mortality rate noted in this condition may be related to the inheritance of a lethal genetic mutation or to neural compression from reduced intracranial volume. Results are discussed in light of current pathogenic hypotheses for human infants with premature metopic suture synostosis.

Animals↗

Comparative morphology and histochemistry of glands associated with the vomeronasal organ in humans, mouse lemurs, and voles.

The vomeronasal organ (VNO) is a chemosensory structure of the vertebrate nasal septum that has been recently shown to exist in nearly all adult humans. Although its link to reproductive behaviors has been shown in some primates, its functionality in humans is still debated. Some authors have suggested that the human VNO has the capacity to detect pheromones, while others described it as little more than a glandular pit. However, no studies have utilized histochemical techniques that would reveal whether the human VNO functions as a generalized gland duct or a specialized chemosensory organ. Nasal septal tissue from 13 humans (2-86 years old) were compared to that of two adult lemurs (Microcebus murinus) and eight adult voles (four Microtus pennsylvanicus and four Microtus ochrogaster). Sections at selected intervals of the VNO were stained with periodic acid-Schiff (PAS), alcian blue (AB), AB-PAS, and PAS-hematoxylin procedures. Results revealed typical well-developed VNOs with tubuloacinar glands in Microtus and Microcebus. VNO glands were AB-negative and PAS-positive in voles and mouse lemurs. Homo differed from Microtus and Microcebus in having more branched, AB and PAS-positive glands that emptied into the VNO lumen. Furthermore, the human VNO epithelium had unicellular mucous glands (AB and PAS-positive) and cilia, similar to respiratory epithelia. These results demonstrate unique characteristics of the human VNO which at once differs from glandular ducts (e.g., cilia) and also from the VNOs of mammals possessing demonstrably functional VNO.

Adolescent↗

Age-related changes in intracranial pressure in rabbits with uncorrected familial coronal suture synostosis.

OBJECTIVE: Chronic, elevated intracranial pressure (ICP) in craniosynostotic infants may result in ocular and neurocapsular problems; however, not all infants exhibit elevated ICP. Clinical ICP studies are further confounded by small and heterogeneic samples, multiple-suture involvement, and varying surgical management protocols. The present study was designed to describe longitudinal changes in ICP in a large, homogenous sample of rabbits with uncorrected familial, nonsyndromic coronal suture synostosis. METHODS: Ninety-one rabbits were divided into four groups: (1) normal rabbits (n = 28), (2) rabbits with delayed-onset coronal suture synostosis (DOCS; n = 25), (3) rabbits with unilateral coronal suture synostosis (UCS; n = 12), and (4) rabbits with bilateral coronal suture synostosis (BCS; n = 26). ICP was measured at 24 and 42 days of age using a Codman epidural microtransducer. RESULTS: Rabbits with BCS had a significantly (p < .05) higher mean ICP at 25 days of age than rabbits in the other three groups by approximately 146%. However, by 42 days of age, mean ICP in normal control rabbits and rabbits with DOCS was significantly (p < .01) increased compared with their mean ICP values seen at 25 days of age, while mean ICP in BCS rabbits significantly (p < .01) decreased (by 32%) over the same time period. ICP in rabbits with UCS was between that seen in normal control rabbits and rabbits with BCS and did not significantly (p > .05) change over time. CONCLUSIONS: These findings suggest that the degree of suture involvement may be related to early increases in ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are discussed.

Aging↗

Coronal suture response to distraction osteogenesis in rabbits with delayed-onset craniosynostosis.

Recent studies have identified a subpopulation of persons with craniosynostosis who exhibit progressive or delayed-onset synostosis and mild cranial vault deformities. These persons may be good candidates for nonextirpation distraction osteogenesis. The present studies were designed to determine force-displacement parameters and assess the effects of distraction osteogenesis on coronal suture growth and morphologic characteristics in a rabbit model with congenital, delayed-onset craniosynostosis. Data were collected from a total of 178 rabbits: 71 normal controls; 16 normal controls with distraction; 72 with delayed-onset coronal suture synostosis; and 19 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the coronal suture. In the force-displacement study, force-displacement distractors were placed across the coronal suture and distracted acutely for 1.0 mm at 42 days of age. Force-displacement curves for the coronal suture were best described by a third-order polynomial regression equation for both normal and synostosed groups. Significant differences (P < 0.05) were found in the mean force necessary to distract a normal suture 1 mm in distance (13.72 kg) compared with a suture with delayed-onset synostosis (48.39 kg). A significant (P < 0.05) relationship was also found between the extent of synostosis and the distractive force in rabbits with delayed-onset synostosis. In the distraction study, internal distractors were fixed across the coronal suture at 25 days of age and percutaneously and intermittently activated at an average of 0.11 mm/day for 42 days (4.54 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis and distraction had significantly (P < 0.01) more coronal suture growth rates compared with rabbits with delayed-onset synostosis and no distraction. Coronal sutures were harvested at 84 days of age for qualitative histologic examination. Normal, distracted coronal sutures showed widened sutural ligaments and thin, active osteogenic fronts. In contrast, distracted coronal sutures from rabbits with delayed-onset synostosis showed narrowed sutural ligaments, thickened and blunt osteogenic fronts, and increased collagen and bony matrix deposition compared with controls. Results suggest that distraction osteogenesis without corticotomy may be a treatment alternative in persons with progressive, delayed-onset synostosis. However, these preliminary data also suggest that distractive forces may accelerate or stimulate osteogenesis differentially in persons with craniosynostosis, possibly through an underlying genetic disorder of bone and cytokine regulation. These differential osteogenic responses to distraction, if validated clinically, will need to be taken into account when planning distraction rate and rhythm protocols for patients with craniosynostosis.

Age of Onset↗

Increased intracranial pressure after coronal suturectomy in craniosynostotic rabbits.

It has been suggested that the complications associated with intracranial hypertension in craniosynostotic infants may be managed with surgical release of the synostosed sutures. However, both postoperative increases and decreases in intracranial pressure (ICP) have been reported in heterogeneous samples of infants with syndromic and nonsyndromic craniosynostoses. The present study was designed to describe longitudinal changes in ICP in a homogeneous sample of rabbits with uncorrected and corrected familial coronal suture synostosis and compare them with age-matched normal control rabbits. Fifty-three rabbits were divided into three groups: normal rabbits (n = 28), rabbits with uncorrected bilateral coronal suture synostosis (n = 9), and rabbits with bilateral coronal suture synostosis with coronal suturectomy at 25 days of age (n = 16). ICP was measured at 25 and 42 days of age using a Codman epidural microtransducer. Results revealed that rabbits with uncorrected craniosynostosis had significantly (P < 0.05) higher ICP at 25 days of age than normal control rabbits by approximately 86%. However, by 42 days of age, ICP in normal rabbits increased by 75%, whereas ICP in rabbits with uncorrected craniosynostosis decreased by 69% over the same time. Synostotic rabbits with coronal suturectomy showed a 50% decrease in ICP immediately after surgical release and then followed the normal, age-related ICP pattern, which significantly increased by 75% at 42 days of age. Results suggest that, in the rabbit model, the postsuturectomy rise in ICP may simply be normal, age-related changes, although a longer follow-up will be needed to determine the recurrence of pathological ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are also discussed.

Analysis of Variance↗

Three-dimensional analysis of craniofacial form in a familial rabbit model of nonsyndromic coronal suture synostosis using Euclidean distance matrix analysis.

OBJECTIVE: Simple craniosynostoses produce predictable morphologies of the cranial vault, with growth deficits in a direction parallel to the synostosed suture and compensatory growth at sutures that are perpendicular to and attached to the synostosed one. In coronal suture synostosis, anteroposterior growth is inhibited, with compensatory growth in a transverse direction. Information on growth patterns and influence on other craniofacial regions are not as clear. This study tested the hypotheses that (1), both juvenile and adult rabbits with familial, nonsyndromic coronal suture synostosis exhibit significant size and shape differences of the entire craniofacial region relative to normal rabbits as a result of altered growth patterns and that (2), shape differences of the calvaria will precede those of the basicranium. DESIGN: Fifty anatomic landmarks were located on 94 New Zealand white rabbit crania. The crania were divided into a juvenile, six-week-old age category (n = 53) and an adult, 18-week-old category (n = 41) in order to assess shape differences at different ages. Each age category was sorted into three groups based on growth at the coronal suture: normal sutural growth, delayed onset synostosis, and complete synostosis. Landmarks were digitized in three-dimensions, and statistical analyses on shape differences were carried out using Euclidean distance matrix analysis (EDMA). RESULTS AND CONCLUSIONS: Results showed that delayed onset synostosis did not produce craniofacial morphology that was different from normal at any age. However, complete synostosis yielded predictable and global craniofacial shape differences at both ages relative to normal skulls, producing an overall shorter, wider cranium with the most markedly compensating regions in a posterosuperior position of the skull. In addition, delayed onset synostosed crania showed no shape differences in the basicranium, relative to normal crania, suggesting primacy of the calvaria in this model of coronal synostosis. However, further investigations are necessary to verify primacy of the calvaria in this model.

Age Factors↗

Brain growth rates in craniosynostotic rabbits.

OBJECTIVE: It has been suggested that abnormal brain morphology or growth rates may be a primary causal factor of craniosynostosis due, in part, to a lack of normal growth stretch and tension at the sutural margins. The purpose of the present study was to quantify cerebral hemisphere morphology and growth in a rabbit model of nonsyndromic coronal suture synostosis to determine whether cerebral dysmorphology is primary or secondary to synostosis in this model. DESIGN: Fifty-seven brains (114 hemispheres) were examined from 40 normal control rabbits and 17 rabbits with bilateral coronal suture synostosis ranging in age from 25 to 450 days postconception (synostosis occurs at approximately 23 days postconception in this model). The calvariae were removed, the brains were fixed in 10% paraformaldehyde, and in situ bilateral measurements of cerebral hemisphere length and cerebral hemisphere width were obtained using a Wild microscope with a camera lucida attachment and digital caliper. Regression analysis was used to compare cerebral cortex growth rates by age between the two groups. RESULTS: Cerebral hemisphere width and cerebral index regression line slopes had similar y intercepts (23 day postconception) with significantly (p < .05) diverging slopes over time. Normal rabbits increased more rapidly than synostosed rabbits. No significant (p > .05) differences were noted in regression line slopes between groups for cerebral hemisphere length by age or length by width. CONCLUSIONS: Cerebral dysmorphologies are probably a compensatory, secondary (postsynostotic) event and not a primary causal factor of craniosynostosis in this rabbit model of human familial, nonsyndromic coronal suture synostosis.

Aging↗

Searching for the vomeronasal organ of adult humans: preliminary findings on location, structure, and size.

The adult human vomeronasal organ (VNO) has been the focus of numerous recent investigations, yet its developmental continuity from the human fetal VNO is poorly understood. The present study compared new data on the adult human "VNO" with previous findings on the fetal human VNO. Nasal septa were removed from twelve adult human cadavers and each specimen was histologically sectioned. Coronal sections were stained with hematoxylin-eosin and periodic acid-Schiff-hematoxylin. The sections were examined by light microscopy for the presence of VNOs and the anterior paraseptal cartilages (PC). VNOs were quantified using a computer reconstruction technique to obtain VNO length, volume, and vomeronasal epithelium (VNE) volume. Histologically, VNOs and PCs were identified in eleven specimens. VNOs had ciliated, pseudostratified columnar epithelium with goblet cells. Variations (e.g., multiple communications to the nasal cavity) were observed in several specimens. Quantification was possible for 16 right or left VNOs. Right or left VNOs ranged from 3.5 to 11.8 mm in length, from 1.8 to 33.8 x 10(-4)cc in volume, and from 2.7 to 18.1 x 10(-4)cc in VNE volume. Results indicated that the adult human VNO was similar in VNE morphology, lumen shape, and spatial relationships when compared to human fetal VNOs. By comparison with previous fetal VNO measures, mean VNO length, volume, and VNE volume were larger in adult humans. These results support previous suggestions that postnatal VNO growth occurs. Findings on location and spatial relationships of the adult VNO were similar to those seen in human fetuses, but critical questions remain regarding the ontogeny of the vomeronasal nerves and VNE.

Adult↗

A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. I. Synostotic onset, pathology, and sutural growth patterns.

Poswillo has stated, "The more severe anomalies of the calvaria, such as plagiocephaly, Crouzon [syndrome], and Apert syndrome still defy explanation, in the absence of an appropriate animal system to study" (p. 207). This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis. Part 1 presents pathological findings and compensatory sutural growth data from 109 normal rabbits and 82 craniosynostotic rabbits from this colony. Synostotic foci, onset, and progression were described in the calvariae from 102 staged (fetal days 21, 25, 27, 33; term = 30 days) fetuses (39 normal, 63 synostosed). Calvarial suture growth patterns from 10 to 126 days of age were assessed from serial radiographs obtained from 89 rabbits (70 normal rabbits and 19 rabbits with unicoronal suture synostosis) with amalgam bone marker implants. Perinatal results revealed that by fetal day 25 the synostotic focal point in synostotic rabbits consistently originated from the endocortical surface of the calvaria in the middle of the coronal suture at a presumed high-tension, interdigitating zone. Histological analysis revealed hyperostotic osteogenic fronts on the affected side compared with the unaffected side. Postnatal sutural growth data revealed a predictable pattern of plagiocephaly (contralateral coronal sutures growing more than ipsilateral sutures and ipsilateral frontonasal and anterior lambdoidal sutures growing more than contralateral sutures), which resulted in early cranial vault deformities and a double "S" shape torquing towards the affected side. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent cytokine and genetic findings from human craniosynostotic studies.

Animals↗

A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. II. Intracranial contents, intracranial volume, and intracranial pressure.

This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis, and this second part presents neuropathological findings and age-related changes in intracranial volume (ICV) and intracranial pressure (ICP) in 106 normal rabbits and 56 craniosynostotic rabbits from this colony. Brain morphology and anteroposterior length were described in 44 rabbit fetuses and perinates (27 normal; 17 synostosed). Middle meningeal artery patterns were qualitatively assessed from 2-D PCC MRI VENC scans and endocranial tracings from 15, 126-day-old rabbits (8 normal, 7 rabbits with unicoronal synostosis). Brain metabolism was evaluated by assessing 18F-FDG uptake with high-resolution PET scanning in 7, 25-day-old rabbits (3 normal, 4 with unicoronal or bicoronal synostosis). Intracranial contents and ICV were assessed using 3-D CT scanning of the skulls of 30 rabbits (20 normal,10 with unicoronal synostosis) at 42 and 126 days of age. Serial ICP data were collected from 66 rabbits (49 normal; 17 with unicoronal synostosis) at 25 and 42 days of age. ICP was assessed in the epidural space using a Codman NeuroMonitor microsensor transducer. Results revealed that cerebral cortex morphology was similar between normal and synostosed fetuses around the time of synostosis. Significantly (P<0.05) decreased A-P cerebral hemisphere growth rates and asymmetrical cortical remodeling were noted with increasing age in synostotic rabbits. In addition, rabbits with unicoronal suture synostosis exhibited asymmetrical middle meningeal artery patterns, decreased and asymmetrical brain metabolism, a "beaten-copper" intracranial appearance, significantly (P<0.05) decreased ICV, and significantly (P<0.01) elevated ICP compared with normal control rabbits. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent clinical neuropathological, ICV, and ICP findings recorded in human craniosynostotic studies.

Animals↗

Intracranial volume in craniosynostotic rabbits.

Although craniosynostosis alters brain growth direction resulting in compensatory changes in the neurocranium, it has been suggested that such compensations occur with little reduction in intracranial volume (ICV). This hypothesis was tested in a rabbit model with nonsyndromic, familial coronal suture synostosis. Cross-sectional three-dimensional computed tomographic head scans were obtained from 79 rabbits (25 normal, 28 with delayed-onset synostosis, and 26 with early-onset synostosis) at 25, 42, and 126 days of age. Intracranial contents were reconstructed and indirect ICV was calculated. Results revealed that by 25 days of age the intracranial contents from early-onset synostosed rabbit skulls showed rostral (anterior) constrictions and a "beaten copper" morphology in the parietal and temporal regions compared with the other two groups. These deformities increased in severity with age. Quantitatively, ICV was significantly reduced (P < 0.05) by 7% in rabbits with early-onset synostosis compared with both control rabbits and rabbits with delayed-onset synostosis at 25 days of age. By 126 days of age, ICV in rabbits with synostosis was significantly reduced (p < 0.05) by 11% in early-onset synostosis and by 8% in delayed-onset synostosis compared with normal rabbits. Results suggest that in rabbits with uncorrected craniosynostosis, compensatory changes in the neurocranium were not adequate to allow normal expansion of the neurocapsular matrix. Further research is needed to determine if ICV reduction is correlated with cerebral atrophy or cerebral spinal fluid (i.e., ventricular or subarachnoid) space compression in this model.

Age of Onset↗

Internal calvarial bone distraction in rabbits with delayed-onset coronal suture synostosis.

Recent studies have identified a subpopulation of craniosynostotic individuals who exhibit progressive or delayed-onset synostosis and mild craniofacial growth abnormalities. These individuals may be good candidates for nonextirpation, distraction osteogenesis therapy. The present study was designed to test this hypothesis by using internal calvarial bone distraction in a rabbit model with familial delayed-onset craniosynostosis. Data were collected from 159 rabbits: 71 normal controls, 72 with delayed-onset coronal suture synostosis, 8 with delayed-onset coronal suture synostosis and coronal suturectomy, and 8 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the frontonasal, coronal, and anterior lambdoidal sutures. At 25 days of age, correction was accomplished through either a 5-mm-wide suturectomy or distraction osteogenesis. An internal distraction appliance was fixed to the frontal and parietal bones and percutaneously and intermittently activated at an average of 0.10 mm/day for 42 days (4.11 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis had significantly (p < 0.01) reduced coronal suture growth rates (0.04 mm/day) compared with the other three groups (0.07 mm/day). Rabbits with suturectomy and rabbits with distraction showed similar coronal suture responses. However, from 42 to 84 days of age, rabbits with distraction showed reduced growth at the vault sutures and abnormal growth patterns in cranial vault width, cranial vault shape, and cranial base angulation compared with the other three groups. Results demonstrated that, although the normal coronal suture growth rate was maintained in rabbits with delayed-onset synostosis using intermittent distraction osteogenesis, normal adult craniofacial structure was not achieved. Such anomalous growth was probably a result of altered growth vectors and compressive forces at adjacent sutures during distraction. These findings suggest that distraction osteogenesis without corticotomy may be a treatment alternative in individuals with progressive, delayed-onset synostosis, but that internal appliances that generate low-level, continuous distractive forces should be investigated and developed.

Animals↗