Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 1: The palate of the term newborn

BACKGROUND: The evidence on prematurity as 'a priori' a risk for palatal disturbances that increase the need for orthodontic or orthognathic treatment is still weak. Further well-designed clinical studies are needed. The objective of this review is to provide a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development. One focus of this review is the analysis of studies on the palate of the term newborn, since knowing what is 'normal' is a precondition of being able to assess abnormalities. METHODS: A search profile based on Cochrane search strategies applied to 10 medical databases was used to identify existing studies. Articles, mainly those published before 1960, were identified from hand searches in textbooks, encyclopedias, reference lists and bibliographies. Sources in English, German, and French of more than a century were included. Data for term infants were recalculated if particular information about weight, length, or maturity was given. The extracted values, especially those from non-English paper sources, were provided unfiltered for comparison. RESULTS: The search strategy yielded 182 articles, of which 155 articles remained for final analysis. Morphology of the term newborn's palate was of great interest in the first half of the last century. Two general methodologies were used to assess palatal morphology: visual and metrical descriptions. Most of the studies on term infants suffer from lack of reliability tests. The groove system was recognized as the distinctive feature of the infant palate. The shape of the palate of the term infant may vary considerably, both visually and metrically. Gender, race, mode of delivery, and nasal deformities were identified as causes contributing to altered palatal morphology. Until today, anatomical features of the newborn's palate are subject to a non-uniform nomenclature. CONCLUSION: Today's knowledge of a newborn's 'normal' palatal morphology is based on non-standardized and limited methodologies for measuring a three-dimensional shape. This shortcoming increases bias and is the reason for contradictory research results, especially if pathologic conditions like syndromes or prematurity are involved. Adequate measurement techniques are needed and the 'normal palatal morphology' should be defined prior to new clinical studies on palatal development

Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo

Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 3: Discussion and Conclusion

BACKGROUND: It has been hypothesized that prematurity and adjunctive neonatal care is 'a priori' a risk for disturbances of palatal and orofacial development which increases the need for later orthodontic or orthognathic treatment. As results on late consequences of prematurity are consistently contradictory, the necessity exists for a fundamental analysis of existing methodologies, confounding factors, and outcomes of studies on palatal development in preterm and low birthweight infants. METHOD: A search of the literature was conducted based on Cochrane search strategies including sources in English, German, and French. Original data were recalculated from studies which primarily dealt with both preterm and term infants. The extracted data, especially those from non-English paper sources, were provided unfiltered in tables for comparison (Parts 1 and 2). RESULTS: Morphology assessment of the infant palate is subject to non-standardized visual and metrical measurements. Most methodologies are inadequate for measuring a three-dimensional shape. Several confounding factors were identified as causes contributing to disturbances of palatal and orofacial development. CONCLUSION: Taking into account the abovementioned shortcomings, the following conclusions may be drawn for practitioners and prospective investigators of clinical studies. 1) The lack of uniformity in the anatomical nomenclature of the infant's palate underlines the need for a uniform definition. 2) Metrically, non-intubated preterm infants do not exhibit different palatal width or height compared to matched term infants up to the corrected age of three months. Beyond that age, no data on the subject are currently available. 3) Oral intubation does not invariably alter palatal morphology of preterm and low birthweight infants. 4) The findings on palatal grooving, height, and asymmetry as a consequence of orotracheal intubation up to the age of 11 years are inconsistent. 5) Metrically, the palates of orally intubated infants remain narrower posteriorly, beginning at the second deciduous molar, until the age of 11 years. Beyond that age, no data on the subject are currently available. 6) There is a definite need for further, especially metrical, longitudinal and controlled trials on palatal morphology of preterm and low birthweight infants with reliable measuring techniques. 7) None of the raised confounding factors for developmental disturbances may be excluded until evident results are presented. Thus, early orthodontic and logopedic control of formerly premature infants is recommended up to the late mixed dentition stage

Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 2: The palate of the preterm/low birthweight infant

BACKGROUND: Well-designed clinical studies on the palatal development in preterm and low birthweight infants are desirable because the literature is characterized by contradictory results. It could be shown that knowledge about 'normal' palatal development is still weak as well (Part 1). The objective of this review is therefore to contribute a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development in preterm and low birthweight infants. METHODS: An electronic literature search as well as hand searches were performed based on Cochrane search strategies including sources of more than a century in English, German, and French. Original data were recalculated from studies which primarily dealt with both preterm and term infants. The extracted data, especially those from non-English paper sources, were provided unfiltered for comparison. RESULTS: Seventy-eight out of 155 included articles were analyzed for palatal morphology of preterm infants. Intubation, feeding tubes, feeding mode, tube characteristics, restriction of oral functions, kind of diet, cranial form and birthweight were seen as causes contributing to altered palatal morphology. Changes associated with intubation concern length, depth, width, asymmetry, crossbite, and contour of the palate. The phenomenon 'grooving' has also been described as a complication associated with oral intubation. However, this phenomenon suffers from lack of a clear-cut definition. Head flattening, pressure from the oral tube, pathologic or impaired tongue function, and broadening of the alveolar ridges adjacent to the tube have been raised as causes of 'grooving'. Metrically, the palates of intubated preterm infants remain narrower, which has been examined up to the age of the late mixed dentition. CONCLUSION: There is no evidence that would justify the exclusion of any of the raised causes contributing to palatal alteration. Thus, early orthodontic and logopedic control of formerly orally intubated preterm infants is recommended, as opposed to non-intubated infants. From the orthodontic point of view, nasal intubation should be favored. The role that palatal protection plates and pressure-dispersing pads for the head have in palatal development remains unclear

Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's