Early origin and colonization of the developing central nervous system by microglial precursors.
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Animals↗
Biomedical subjects
J Navascués
Publications and source records attributed to J Navascués.
Response of macrophage/microglial cells to experimental neuronal degeneration in the avian isthmo-optic nucleus during development.
Blockade of the retrograde axonal transport of isthmo-optic nucleus (ION) neurons in the avian embryo results in their massive degeneration. We used this system to investigate the response of macrophage/microglial cells to neuronal degeneration in the embryonic brain. Colchicine was injected into the right eye of quail or chick embryos at a time when the survival of ION neurons depends on retrograde trophic support from the retina, and the chronology of the subsequent macrophage/microglial response in the ION was analyzed. This response was restricted to the ION contralateral to the injected eye; no modifications of the normal state were observed in the surrounding parenchyma or in the opposite ION, used as control. The response was first detected 18 hours after the colchicine injection (18 hours pi), when an increase of the macrophage/microglial cell number was evident. The number of these cells in the affected ION increased, peaking at 40-48 hours pi. At later survival times, macrophage/microglial cells were progressively less abundant in the affected ION, which gradually diminished in size. At 120 hours pi the only remnant of the ION was a small cluster of macrophage/microglial cells, surrounded by a clear area with scarce nonmicroglial cells, in the region formerly occupied by the ION. This study reveals that a strong macrophage/microglial response occurs in the embryonic brain in response to neuronal degeneration but that these cells do not trigger the neuronal death, as they only appear after pyknotic fragments are already observable.
Animals↗
Entry, dispersion and differentiation of microglia in the developing central nervous system.
Microglial cells within the developing central nervous system (CNS) originate from mesodermic precursors of hematopoietic lineage that enter the nervous parenchyma from the meninges, ventricular space and/or blood stream. Once in the nervous parenchyma, microglial cells increase in number and disperse throughout the CNS; these cells finally differentiate to become fully ramified microglial cells. In this article we review present knowledge on these phases of microglial development and the factors that probably influence them.
Animals↗
[Obstetric trauma. A current problem?].
Advances in obstetric practice have decreased birth traumas in the last years, although they are still an important chapter in neonatal age. Between 1993-1998 a total of 21,375 stillborns were registered with a total of 309 birth injuries in 303 neonates (1.44%). The diagnoses were: 2 liver subcapsular hematomas, 105 cephalohematomas, 16 parietal fractures, 11 subdural hemorrhages, 107 clavicular fractures, 10 miscellaneous fractures, 8 soft tissue injuries, 25 facial nerve injuries and 25 braquial palsy. About relation between type of labor and birth trauma was found that clavicular fracture and cephalic vaginal delivery were associated in 50% of the cases, cephalohematoma and forceps in 51%, braquial palsy and vaginal delivery in 44% and forceps in 36%. High weight at birth was another risk factor for entities such as clavicular fracture and braquial palsy. We conclude that birth trauma is a pathology with a relevant incidence and their epidemiology factor had to be known.
Birth Injuries↗
Naturally occurring cell death and migration of microglial precursors in the quail retina during normal development.
We compared chronotopographical patterns of distribution of naturally occurring neuronal death in the ganglion cell layer (GCL) and the inner nuclear layer (INL) with patterns of tangential and radial migration of microglial precursors during quail retinal development. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling technique, and microglial precursors were identified by immunocytochemistry with an antibody recognizing quail microglial cells (QH1 antibody). Apoptotic cells were first detectable in the GCL at the seventh day of incubation (E7), were most abundant at E10, and were absent after E13. In the INL, apoptotic cells first appeared at E7, were most abundant at E12, and disappeared entirely after the third posthatching day (P3). In both retinal layers, cell death first appeared in a small central area of the retina and subsequently spread along three gradients: central-to-peripheral, temporal-to-nasal, and dorsal-to-ventral. The chronology of tangential (between E7 and E16) and radial migration (between E8 and P3) of microglial precursors was highly coincident with that of cell death in the GCL and INL. Comparison of the chronotopographical pattern of distribution of apoptotic nuclei in the GCL with the patterns of tangential and radial migration of microglial precursors neither supported nor refuted the hypothesis that ganglion cell death is the stimulus that triggers the entry and migration of microglial precursors in the developing retina. However, microglial cells in most of the retina traversed the INL only after cell death had ceased in this layer, suggesting that cell death in the INL does not attract microglial precursors migrating radially. Dead cell debris in this layer was phagocytosed by Müller cells, whereas migrating microglial cells were seen phagocytosing apoptotic bodies in the nerve fiber layer and GCL but not in the INL.
Aging↗
Circumferential migration of ameboid microglia in the margin of the developing quail retina.
Central-to-peripheral migration of QH1-positive microglial precursors occurs in the vitrealmost part of the developing quail retina. This study shows that some QH1-positive ameboid cells with morphological features of migrating cells are already present in the margin of the retina before microglial precursors migrating centrally to peripherally arrive in this zone. Because the earlier cells are oriented parallel to the ora serrata, we deduce that some microglial cells migrate circumferentially in the margin of the retina, whereas other microglial precursors migrate from central to peripheral zones. Microglial cells that migrate circumferentially are first seen on embryonic day 6 (E6) and advance in a temporal-to-dorsal-to-nasal direction from the temporoventral quadrant of the retina. When cells migrating centrally to peripherally reach the retinal margin, they meet those migrating circumferentially. From E6 on, some QH1-positive dendritic cells in the ciliary body bear processes that penetrate the retina, where they are oriented circumferentially. These observations suggest that microglial cells that migrate circumferentially in the retinal margin share a common origin with dendritic cells of the ciliary body. Therefore, microglial cells of the quail retina appear to make up a heterogeneous population, with some cells originating from the pecten/optic nerve head area and others from the ciliary body.
Aging↗
Proliferation of actively migrating ameboid microglia in the developing quail retina.
Sheets containing the inner limiting membrane covered by a carpet of Müller cell endfeet were used to show that ameboid microglial cells migrating tangentially in the vitreal part of the developing retina of quail embryos underwent mitosis. Double labeling with anti-beta-tubulin/QH1 or Hoechst 33342/QH1 revealed that some migroglial cells with morphological features typical of active migration were in early prophase. By anaphase and early telophase, microglial cells had retracted their lamellipodia and were ovoid in shape. Later in telophase, but well before completion of cytokinesis, both daughter cells again emitted lamellipodia, thus regaining the typical morphology of migrating cells. We concluded that ameboid microglial cells go through cycles in which migration and mitosis alternate, and that both mechanisms contribute to the spread of microglia throughout the developing retina. The mitotic spindle of dividing microglial cells showed different orientations, which probably influenced the course of subsequent migration. The expression of the proliferating cell nuclear antigen in the nucleus of most tangentially migrating ameboid microglial cells at E9-E10 confirmed their proliferative capability. However, the rate of proliferation of these cells decreased during embryonic development, and was nearly zero at E14.
Animals↗
[UTIscreen versus UROQUICK: two semiautomatic systems for bacteriuria detection].
BACKGROUND: The aim of the study is to find a rapid and reliable method for urine screen. With this purpose two semiautomatic systems have been evaluated: UTIscreen and UROQUICK. MATERIAL AND METHODS: We have carried out a prospective study of a total 1,070 urine specimens from patients with suspected urinary infection. Each sample has been inoculated in the two semiautomatic systems and compared with the semiquantitative plate culture as the reference method. RESULTS: Both semiautomatic systems showed similar specificity and sensitivity at an interpretative breakpoint of 30,000 CFU/ml, with a low number of false positives. Uninfected specimens can be reported the same day of reception. CONCLUSIONS: Both UTIscreen and UROQUICK systems seem to be adequate for urinary tract infection screening. They are reliable and easy to perform, but in our particular case we find advantage in using UTIscreen because the faster reading of this system makes posible to report the negative results in the same morning of reception of the specimen and do the culture of all the positive samples during our usual working schedule.
Bacteriuria↗
Tangential migration of ameboid microglia in the developing quail retina: mechanism of migration and migratory behavior.
Long distance migration of microglial precursors within the central nervous system is essential for microglial colonization of the nervous parenchyma. We studied morphological features of ameboid microglial cells migrating tangentially in the developing quail retina to shed light on the mechanism of migration and migratory behavior of microglial precursors. Many microglial precursors remained attached on retinal sheets containing the inner limiting membrane covered by a carpet of Müller cell endfeet. This demonstrates that most ameboid microglial cells migrate tangentially on Müller cell endfeet. Many of these cells showed a central-to-peripheral polarized morphology, with extensive lamellipodia spreading through grooves flanked by Müller cell radial processes, to which they were frequently anchored. Low protuberances from the vitreal face of microglial precursors were firmly attached to the subjacent basal lamina, which was accessible through gaps in the carpet of Müller cell endfeet. These results suggest a mechanism of migration involving polarized extension of lamellipodia at the leading edge of the cell, strong cell-to-substrate attachment, translocation of the cell body forward, and retraction of the rear of the cell. Other ameboid cells were multipolar, with lamellipodial projections radiating in all directions from the cell body, suggesting that microglial precursors explore the surrounding environment to orient their movement. Central-to-peripheral migration of microglial precursors in the retina does not follow a straight path; instead, these cells perform forward, backward, and sideways movements, as suggested by the occurrence of (a) V-shaped bipolar ameboid cells with their vertex pointing toward either the center or the periphery of the retina, and (b) threadlike processes projecting from either the periphery-facing edge or the center-facing edge of ameboid microglial cells.
Animals↗
The origin and differentiation of microglial cells during development.
Some authors claim that microglia originate from the neuroepithelium, although most now believe that microglial cells are of mesodermal origin, and probably belong to the monocyte/macrophage cell line. These cells must enter the developing central nervous system (CNS) from the blood stream, the ventricular space or the meninges. Afterward microglial cells are distributed more or less homogeneously through the entire nervous parenchyma. Stereotyped patterns of migration have been recognized during development, in which long-distance tangential migration precedes radial migration of individual cells. Microglial cells moving through the nervous parenchyma are ameboid microglia, which apparently differentiate into ramified microglia after reaching their definitive location. This is supported by the presence of cells showing intermediate features between those of ameboid and ramified microglia. The factors that control the invasion of the nervous parenchyma, migration within the developing CNS and differentiation of microglial cells are not well known. These phenomena apparently depend on environmental factors such as soluble or cell-surface bound molecules and components of the extracellular matrix. Microglial cells within the developing CNS are involved in clearing cell debris and withdrawing misdirected or transitory axons, and presumably support cell survival and neurite growth.
Animals↗
[Bacteremia by Sphingomonas paucimobilis].
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Bacteremia↗
Microglia development in the quail cerebellum.
We used the QH1 antibody to study changes in the morphological features and distribution of microglial cells throughout development in the quail cerebellum. Few microglial precursors were present in the cerebellar anlage before the ninth incubation day (E9), whereas many precursors apparently entered the cerebellum from the meninges in the basal region of the cerebellar peduncles between E9 and E16. From this point of entry into the nervous parenchyma, they spread through the cerebellar white matter, forming a 'stream' of labeled cells that could be seen until hatching (E16). The number of microglial cells in the cerebellar cortex increased during the last days of embryonic life and first posthatching week, whereas microglial density within the white matter decreased after hatching. As a consequence, the differences in microglial cell density observed in the cerebellar cortex and the white matter during embryonic life diminished after hatching, and microglia showed a nearly homogeneous pattern of distribution in adult cerebella. Ameboid and poorly ramified microglial cells were found in developing stages, whereas only mature microglia appeared in adult cerebella. Our observations suggest that microglial precursors enter the cerebellar anlage mainly by traversing the pial surface at the basal region of the peduncles, then migrate along the white matter, and finally move radially to the different cortical layers. Differentiation occurs after the microglial cells have reached their final position. In other brain regions the development of microglia follows similar stages, suggesting that these steps are general rules of microglial development in the central nervous system.
Animals↗
Macrophages during avian optic nerve development: relationship to cell death and differentiation into microglia.
Cell death is frequent during the development of the nervous system. In the developing optic nerve of chicks and quails, neuroepithelial cell death was first observable on the third day of incubation, slightly after the first cell ganglion axons appeared in the stalk. Specialized phagocytes were observed within the stalk in chronological and topographical coincidence with cell death. These cells were identified as macrophages because of their morphological features, intense acid phosphatase activity and, in quail embryos, labeling with QH1, a monoclonal antibody recognizing quail hemangioblastic cells. Macrophages in areas of cell death were round and actively phagocytosed cell debris. We used electron microscopy and histochemical and immunocytochemical labeling to study macrophagic cells of the optic nerve in avian embryos of 3-6.5 days of incubation. As development proceeded, phagocytosing, round macrophages became ameboid macrophages that migrated from areas of cell death toward regions occupied by optic axonal fascicles. Macrophages in these locations were thin and elongated, with a few processes. To elucidate the final fate of macrophagic cells in the optic nerve, sections taken from older embryonic and hatched quails were stained with the QH1 antibody. On the 8th day of incubation some slightly ramified QH1+ cells were present among axonal fascicles. In subsequent stages these cells increased in number and acquired more complex ramifications. In adult optic nerves, QH1+ cells had a small body and sent out slender processes, sometimes with secondary and tertiary branches, which were frequently orientated parallel to the course of the optic axons. These cells were considered to be microglial cells. The appearance of macrophages within the developing optic nerve at the same time as neuroepithelial cell death suggests that cell death influences the recruitment of macrophages into the nerve. When macrophages reach the areas invaded by optic axonal fascicles, they undergo structural and probably also physiological changes that appear to signal differentiation into microglia.
Animals↗
Origin of microglia in the quail retina: central-to-peripheral and vitreal-to-scleral migration of microglial precursors during development.
The origin, migration, and differentiation of microglial precursors in the avascular quail retina during embryonic and posthatching development were examined in this study. Microglial precursors and developing microglia were immunocytochemically labeled with QH1 antibody in retinal whole mounts and sections. The retina was free of QH1+ macrophages at embryonic day 5 (E5). Ameboid QH1+ macrophages from the pecten entered the retina from E7 on. These macrophages spread from central to peripheral areas in the retina by migrating on the endfeet of the Müller cells and reached the periphery of the retina at E12. While earlier macrophages were migrating along the inner limiting membrane, other macrophages continued to enter the retina from the pecten until hatching (E16). From E9 on, macrophages were seen to colonize progressively more scleral retinal layers as development advanced. Macrophages first appeared in the ganglion cell layer at E9, in the inner plexiform layer at E12, and in the outer plexiform layer at E14. Therefore, it seems that macrophages first migrated tangentially along the inner retinal surface and then migrated from vitreal to scleral levels to gain access to the plexiform layers, where they differentiated into ramified microglia. Macrophages appeared to differentiate shortly after arrival in the plexiform layers, as poorly ramified QH1+ cells were seen as early as E12 in the inner plexiform layer and at E14 in the outer plexiform layer. Radial migration of macrophages toward the outer plexiform layer continued until posthatching day 3, after which retinal microglia showed an adult distribution pattern. We also observed numerous vitreal macrophages intimately adhered to the surface of the pecten during embryonic development, when macrophages migrated into the retina. These vitreal macrophages were not seen from hatching onwards, when no further macrophages entered the retina.
Animals↗
Microglia in the avian retina: immunocytochemical demonstration in the adult quail.
Immunocytochemical techniques were used in conjunction with the QH1 antibody to study the morphological characteristics and distribution of microglia in the avascular retina of an avian species (the quail). The majority of microglial cells appeared in the outer and inner plexiform layers throughout the entire retina, whereas a few microglial cells in the nerve fiber layer were seen only in the central zone of the retina, near the optic nerve head. In the outer plexiform layer, microglial cells were star-shaped, with processes that ramified profusely in the horizontal plane. Fine process tips extended outward radially, insinuating themselves among the photoreceptors. A regular mosaic-like arrangement of microglial cells was evident in the outer plexiform layer, with no overlapping between adjacent cell territories. Microglial cells in the inner plexiform layer ramified through the entire width of this layer, showing radial and horizontal processes. Microglia in the inner plexiform layer also tended to be regularly distributed in a mosaic-like fashion, although there was slight overlapping between adjacent cell territories. Microglia density in this layer was approximately twice that in the outer plexiform layer. This pattern of microglial distribution was similar to that described in vascular retinae of several species of mammals, a finding that suggest that blood vessels are not responsible for the final locations of microglia in the adult retina, and that microglial precursors must migrate through long distances before they reach their precise destination.
Animals↗
Development of microglia in the quail optic tectum.
The development of microglia in the quail optic tectum from embryonic day 6 to adulthood was studied by using the QH1 monoclonal antibody. In youngest tecta, microglial cells were scarcely present, but their number rose in subsequent stages. A clear pattern of microglial cell distribution was observable in embryos of 9-16 days. (1) Round cells appeared close to the ventricular layer. (2) Large numbers of ameboid and round labeled cells were seen in the stratum album centrale during development. A gradient of cell density was observable in this layer, as fewer labeled cells appeared in medial regions of the tectum than in lateral regions. (3) Maturing ramified cells were found in layers external to the stratum album centrale, where they increased in number and in branching complexity during development. In adult tecta, almost all microglial cells were of the mature ramified type and were distributed homogeneously in the different tectal layers, although in some layers they had particular morphological features. The distribution of microglia in the developing tectum and in adjacent regions provided insight into the routes of microglial cell invasion of the tectum during development. Apparently, a proportion of microglial cells reached the tectal parenchyma from the meninges and from the ventricular lumen, but the majority of them migrated along nerve fiber tracts from their entry point at the pial surface of the ventromedial caudal tectum. After they reached the stratum album centrale, microglial cells continued their migration toward more external layers, where they differentiated into ramified microglia.
Aging↗
First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system.
A phagocytic cell system of hemopoietic origin exists in the early avian embryo (Cuadros, Coltey, Nieto, and Martin: Development 115:157-168, '92). In this study we investigated the presence of cells belonging to this system in the central nervous system (CNS) of chick and quail embryos by using both histochemical staining for acid phosphatase and immunolabelling with antibodies recognizing cells of quail hemangioblastic lineage. The origin of these cells was traced in interspecific chick-quail yolk sac chimeras. Hemopoietic cells were detected within the CNS from developmental stage HH15 on, and steadily increased in number at subsequent stages. Analysis of yolk sac chimeras revealed that most of these cells were of yolk sac origin, although some hemopoietic cells of intramebryonic origin were also found in the CNS. Immunocytochemical, histochemical, and ultrastructural characterization allowed us to identify hemopoietic cells in the CNS as macrophages. These cells were consistently found in the brain vesicles and spinal cord, appearing (1) between undifferentiated neuroepithelial cells at dorsal levels of the CNS; (2) in areas of cell death; (3) in the marginal layer in close relationship with developing axons; (4) in large extracellular spaces in the subventricular layer; (5) on vascular buds growing through the marginal and subventricular layers; and (6) in the ventricular lumen. Macrophages in different locations varied in morphology and ultrastructure, suggesting that in addition to their involvement in phagocytosis, they play a role in other processes in the developing CNS, such as axonal growth and vascular development. The first macrophages migrate to the CNS independently of its vascularization, apparently traversing the pial basal lamina to reach the nervous parenchyma. Other macrophages may enter the CNS together with vascular buds at subsequent stages during CNS vascularization.
Acid Phosphatase↗
Microglia in the mature and developing quail brain as revealed by a monoclonal antibody recognizing hemopoietic cells.
The monoclonal antibody QH1, which recognizes quail endothelial and hemopoietic cells, was found to label microglia in the developing and mature brain of the quail. Forms of microglia similar to those described in mammals were labelled. Ameboid microglia predominated at embryonic stages, became less numerous in late embryonic development, and disappeared completely by day 10 post-hatch (P10). Poorly ramified microglia were present as early as day 5 of incubation (E5), and were progressively replaced by mature ramified microglia from E14 onwards. From P10 onwards, ramified microglia were the only microglial form seen in the quail brain.
Aging↗