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V H Perry

Publications and source records attributed to V H Perry.

At least 127 records · Page 7Linked to original sources
PubMed1992

Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system.

Neither excitotoxic neurodegeneration nor lipopolysaccharide induces an acute myelomonocytic exudate in the murine central nervous system (CNS) parenchyma (Andersson, P.-B., V. H. Perry, and S. Gordon. 1991. Neuroscience, 42:201; Andersson, P.-B., V. H. Perry, and S. Gordon. 1992. Neuroscience 48:169). In this study formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, interleukin 8 (IL-8), IL-1, or tumor necrosis factor alpha were injected into the hippocampus to assess whether these leukocyte chemotaxins and known mediators of recruitment could bypass this block. They induced morphologic activation of microglia and widespread leukocyte margination but little or no cell exudation into the CNS parenchyma. By contrast, there was acute myelomonocytic cell recruitment to the choroid plexus, meninges, and ventricular system, comparable to that in the skin after subcutaneous injection. The normal CNS parenchyma appears to be a tissue unique in its resistance to leukocyte diapedesis, which is shown here to be at a step beyond chemotactic cytokine secretion or induction of leukocyte adhesion to cerebral endothelium.

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PubMed1992

Role of macrophages in peripheral nerve degeneration and repair.

A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that the degenerating distal segment is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there.

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PubMed1992

Consequences of slow Wallerian degeneration for regenerating motor and sensory axons.

The time course of Wallerian degeneration in the tibial and saphenous nerves was compared in Balb/c mice and mice of the C57BL/Ola strain (Lunn et al., 1989). Axons, particularly myelinated ones, in nerves of C57BL/Ola mice are very slow to degenerate, many still being present 3 weeks after axotomy. Nuclear numbers in the distal stump peak much later and do not reach the levels found in Balb/c mice; debris removal is very slow, and Schwann cell numbers only rise slightly above normal levels in the long term. Regeneration was investigated electrophysiologically and by electron microscopy (EM). Myelinated sensory axons regenerated slowly and incompletely compared with motor ones which were only slightly slowed after nerve crush (although they were significantly hindered after nerve section). Total myelinated axon numbers were still some 20% less than normal even after 200 days in sensory nerves. Even after all axons had degenerated in C57BL/Ola mice, regeneration rates of neither myelinated nor unmyelinated sensory axons reached those achieved in Balb/c mice. It is concluded that while regeneration can eventually proceed slowly when Wallerian degeneration is much delayed, the usual rapid time course of Wallerian degeneration is necessary if axons, particularly sensory ones, are to regenerate at optimal rates and to maximum extent. While local obstruction to axon growth probably impedes the early phase of regeneration in C57BL/Ola mice, it seems possible that a lack of adequate early signals affects regeneration permanently by minimizing the cell body reaction to injury.

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PubMed1992

Stromal macrophages of the choroid plexus situated at an interface between the brain and peripheral immune system constitutively express major histocompatibility class II antigens.

Using immunocytochemistry we have shown that there is a population of macrophages within the stroma of the choroid plexus of rats and mice which expresses high levels of major histocompatibility complex Class II antigens. In whole mount preparations of the choroid plexus, the morphology and regular distribution of these cells is similar to the Langerhans cells of the skin. These cells reside at an important interface between the central nervous system and the peripheral immune system and their possible role in immune-mediated diseases of the central nervous system is discussed.

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PubMed1992

The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues.

Acute inflammation is important for defence against infection, wound repair and the mediation of auto-immune tissue destruction. Myelomonocytic recruitment in acute inflammation is a stereotyped and non-specific response to tissue insult which begins within 2 h. In this study, lipopolysaccharide was injected into the murine CNS and other body sites of mice to compare the inflammatory responses. Doses of lipopolysaccharide which induced typical myelomonocytic recruitment in skin and the choroid plexus had no effect in CNS parenchyma, apart from the morphological activation of local resident microglia. The CNS parenchymal response proceeded independently of that in the choroid plexus-cerebral ventricles and had three distinct and unique phases. Initially there was minimal neutrophil exudation and a two-day delay before any increase in macrophage-microglial cell number. Next, there was a rapid increase in macrophage-microglial cell numbers during the third day, mainly due to recruitment of blood monocytes. During this phase, leukocyte recruitment was restricted to monocytes which rapidly adopted the arborized microglial phenotype. Monocytes migrated through an intact blood-brain barrier independent of changes in solute permeability. Finally, there was a florid myelomonocytic reaction predominantly in the white matter, one week after intracerebral injection of 2 micrograms lipopolysaccharide. At this time, the leukocyte reaction disrupted the blood-brain barrier, mononuclear phagocytes expressed macrophage morphology and abundant major histocompatibility complex Class II antigen, and T lymphocytes were present. Myelomonocytic entry into the CNS was partially inhibited by prior blockade of the type 3 complement receptor, known to mediate leukocyte adhesion to endothelium elsewhere. The processes which lead to rapid myelomonocytic recruitment in other tissues are absent in CNS parenchyma. Understanding the molecular mechanisms responsible could have considerable significance both for CNS pathophysiology as well as possible anti-inflammatory therapeutic application elsewhere in the body.

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PubMed1992

Turnover of resident microglia in the normal adult mouse brain.

We undertook this study to determine whether the microglia, the resident macrophages of the central nervous system, turn over in the steady-state. The turnover of brain macrophages would lend support to the "Trojan Horse" hypothesis of central nervous system infection, since one origin of replacement cells is the circulating monocyte pool. We combined the immunohistochemical detection of F4/80, a specific macrophage marker, with [3H]thymidine incorporation and autoradiography in normal adult mice. We could detect double-labelled cells in the brains of mice perfused 60 min after isotope administration. Such cells were few in number, randomly scattered throughout the brain and had the morphology of typical resident cells. The labelling index at this survival time was 0.052 +/- 0.003%. Thus resident microglia can synthesise DNA in situ. After longer survival times, we detected larger numbers of double-labelled cells. F4/80+ cells with resident morphology, mitotic figures, pairs of closely apposed (daughter) cells and cells with rounded macrophage-like morphology, all exhibited silver labelling. Twenty-four hours after isotope administration the labelling index was 0.192 +/- 0.052%. From morphologic evidence and comparison of labelling indices at different survival times, we concluded that: (i) resident microglia can synthesise DNA and go on to divide in situ; (ii) cells are recruited from the circulating monocyte pool through an intact blood-brain barrier and rapidly differentiate into resident microglia. We estimate that the two processes contribute almost equally to the steady-state turnover of resident microglia.

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PubMed1992

Macrophages and nerve regeneration.

Macrophages are not only phagocytic cells but also secrete a plethora of growth factors that are potentially important for regeneration. This review will examine the emerging evidence of a likely contribution by macrophages to axonal regeneration.

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PubMed1992

Visual effects of damage to P ganglion cells in macaques.

Four indices of visual performance were measured in control macaques and in macaques that had been exposed to monomeric acrylamide, a neurotoxicant that preferentially damages P retinal ganglion cells. Morphological examination of the retina and visual pathways of these monkeys showed virtually complete loss of P ganglion cells over a region extending to at least 40 deg from the fovea, and relative sparing of M ganglion cells. The four tests examined visual functions for which the visual pathway from P ganglion cells might be of great importance: visual acuity, contrast discrimination, hyperacuity, and shape discrimination. In the acrylamide-dosed monkeys, visual acuity was reduced slightly more than fourfold, a somewhat larger reduction than that seen previously after ibotenic-acid lesions of the P pathway in the geniculate. The residual acuity was in good agreement with the Nyquist frequency calculated from the density of ON or OFF M ganglion cells. Contrast increment thresholds were elevated for the dosed monkeys only in one of the two conditions tested. The elevation was found only under those spatiotemporal conditions for which we have previously shown that contrast thresholds are increased by acrylamide exposure, and was most marked at low background contrasts. Vernier acuity was elevated in one dosed monkey, but not affected in a second monkey that also had severe loss of P ganglion cells. Finally, we found no effect of acrylamide exposure on the number of training trials required to learn simple or complex shape discriminations. These results support previous findings in showing that the P pathway mediates visual acuity, and they show that several other important aspects of visual perception are not exclusively dependent on the P pathway.

Acrylamide↗
PubMed1992

The inflammatory response in the CNS.

In recent years it has been recognized that cells of the mononuclear phagocyte lineage, macrophages and microglia, are a major component of gliosis. We review here studies on the kinetics of the myelomonocytic response to acute excitotoxin induced neuronal degeneration and following the injection of endotoxin (LPS) into the parenchyma of the central nervous system. These studies have shown that the kinetics of myelomonocytic recruitment to the parenchyma of the central nervous system is quite unlike that of other tissues; the polymorphonuclear cells are largely excluded and monocytes are only recruited after a delay of several days. The unusual nature of the inflammatory response in the central nervous system needs to be considered when drawing parallels with the acute inflammatory response in other tissues.

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PubMed1992

The Effectiveness of the Gene Which Slows the Rate of Wallerian Degeneration in C57BL/Ola Mice Declines With Age.

The rate of Wallerian degeneration is unusually slow in severed axons of mice of the C57BL/Ola strain. Within mice of that strain we have now found that the rate of degeneration increases with the age of the animal. In 4-week-old mice nerve stimulation evokes muscle contractions even 5 days after sciatic nerve section and compound action potentials can be recorded in the distal nerve stump up to 3 weeks after section. In 1-year-old animals no action potentials can be excited 5 days after nerve section. Heterozygous mice carrying only one copy of the dominant gene show the same age-related decline in viability of the distal nerve stump after axotomy, and the rate of decline is no greater than for homozygous mice. The more rapid rate of degeneration of severed axons of mice of the C57BL/6J strain was affected in the opposite way by age, degeneration occurring more slowly in older animals.

Journal Article↗
PubMed1992

The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia.

In vitro the expression of a sialic acid-binding receptor on murine macrophages, sialoadhesin, is regulated by exposure to an inducing agent present in serum. We have used immunocytochemistry to examine the macrophage populations of the nervous system in order to test whether this serum inducing agent (SIA) also regulates sialoadhesin expression in vivo and whether plasma proteins may influence the phenotype of macrophages of the nervous system. Microglia, the resident macrophages of the central nervous system, reside behind the blood-brain barrier and do not express sialoadhesin. Microglia and macrophage populations in the cicumventricular organs, choroid plexus and leptomeninges are exposed to plasma proteins and some macrophages express sialoadhesin at these sites. Injury to the CNS, which damages the blood-brain barrier, induces sialoadhesin expression on a proportion of macrophages and microglia within the parenchyma. The expression of sialoadhesin matches the temporal and spatial distribution of the plasma extravasation into the brain parenchyma. These experiments show that exposure to SIA is necessary for sialoadhesin expression and lend further support to the idea that the phenotype of microglia is in part regulated by the presence of the blood-brain barrier.

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PubMed1991

The CNS acute inflammatory response to excitotoxic neuronal cell death.

Acute inflammation is a stereotyped non-specific response to tissue injury which results in the recruitment of neutrophils and monocytes within minutes. In this study the myelomonocytic and microglial reaction to neuronal destruction following unilateral hippocampal injection of kainic acid neurotoxin was investigated. Despite extensive acute neuronal necrosis and notwithstanding a leaky blood-brain-barrier, there is no neutrophil recruitment and a 2-day delay before any increase in macrophage-microglial cell numbers. Resident microglia are capable of reversible upregulation to an activated morphology and the macrophage-microglial reaction is seen not only at the injection site, but also at distant sites related to the axonal pathways and synaptic terminals of the killed neurons.

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PubMed1991

The kinetics and morphological characteristics of the macrophage-microglial response to kainic acid-induced neuronal degeneration.

Outside the nervous system myelomonocytic cells are known to play an important role in the inflammatory response and tissue repair after injury. In this study we have examined the myelomonocytic response to neuronal destruction following unilateral injection of the excitotoxin kainic acid into the mouse hippocampus. Intrahippocampal injection of kainate induces rapid, synchronous neuronal death. There is no neutrophil recruitment and a delay of at least 48 h before macrophage-microglial cell numbers increase. The microglial reaction in the injected hippocampus consists of altered morphology, a 6-9-fold increase in mononuclear phagocyte cell numbers and enhanced expression of the macrophage-specific plasma membrane antigen, F4/80, assessed immunohistochemically and by Western blotting. Microglia also respond at distant sites related to the projection pathway and terminals of killed pyramidal cells but the reaction varies in cell numbers, kinetics and morphology. The absence of neutrophil recruitment and the delay in an increase in macrophage or microglial cells shows that the CNS differs from other sites in the body with regard to the kinetics and nature of the myelomonocytic cell inflammatory response. The role of mononuclear phagocytes in tissue repair in the CNS remains to be defined.

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PubMed1991

The topography of magnocellular projecting ganglion cells (M-ganglion cells) in the primate retina.

The projection from the retina to the dorsal lateral geniculate nucleus in the primate arises from two morphologically distinct types of ganglion cells. The P-ganglion cells project to the parvocellular layers, the M-ganglion cells to the magnocellular layers. We have developed a neurofibrillar stain which stains the M-ganglion cell population with a high degree of selectivity allowing us to map their distribution across the retina. As with other ganglion cell types the M-ganglion cell density peaks close to the fovea and declines towards the periphery. At 1 mm from the fovea the proportion of M-ganglion cells ranges from 6 to 10% and then increases to about 8-10% over much of the retina except along the nasal horizontal meridian. Along the nasal horizontal meridian the percentage increases from 10% at 7 mm eccentricity to 20% or more at higher eccentricities. The increased percentage of M-ganglion cells in the nasal quadrant of the retina correlates with the relatively smaller dendritic trees of M-ganglion cells in this region.

Animals↗
PubMed1991

Delayed response to denervation in muscles of C57BL/Ola mice.

Muscle fibre areas and numbers, tetanic force, resident macrophage numbers and acetylcholine sensitivity were measured in normal and denervated soleus muscles of C57BL/Ola mice for comparison with data from outbred and other inbred strains. Serum creatine kinase levels were also measured. The muscles of normal C57BL/Ola mice had more fibres, generated more tension, had fewer resident macrophages and had a lower acetylcholine sensitivity than muscles of other strains. The normal level of serum creatine kinase was lower in C57BL/Ola mice than in Balb/c mice. Following denervation, the mean cross-sectional area of muscle fibres in Balb/c mice started to fall from day 1 but a fall was not seen in muscles from C57BL/Ola mice until day 5. The development of increased acetylcholine sensitivity was slower in the C57BL/Ola mice although the values in all mouse strains had converged by five days. The levels of serum creatine kinase also rose more slowly following denervation in C57BL/Ola mice. The differences between the data from C57BL/Ola mice and others are ascribed to the slow rate of Wallerian degeneration in that strain. The results support the view that the effects of denervation on muscle are due to both inactivity and an inflammatory effect contributed by nerve degeneration. The mutation that causes slow nerve degeneration may, however, also affect muscle directly, making it more resistant to catabolism.

Acetylcholine↗
PubMed1991

Macrophage dependence of peripheral sensory nerve regeneration: possible involvement of nerve growth factor.

The levels of NGF and NGF receptor mRNA, the degree of macrophage recruitment, and the ability of sensory and motor axons to regenerate were measured in C57BL/Ola mice, in which Wallerian degeneration following a nerve lesion is very slow. Results were compared with those from C57BL/6J and BALB/c mice, in which degeneration is normal. We found that in C57BL/Ola mice, apart from the actual lesion site, recruitment of macrophages was much lower, levels of mRNA for both NGF and its receptor were raised only slightly above normal, and sensory axon regeneration was much impaired. Motor axons regenerated quite well. These results provide in vivo evidence that macrophage recruitment is an important component of NGF synthesis and of sensory (but not motor) axon maintenance and regrowth.

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