Search PubMed⌕ Search

Biomedical subjects

V H Perry

Publications and source records attributed to V H Perry.

At least 109 records · Page 6Linked to original sources
PubMed1994

M and P retinal ganglion cells of diurnal and nocturnal New-World monkeys.

M and P retinal ganglion cell morphology revealed by biocytin retrograde labelling was compared in two closely related New-World monkeys, Cebus and Aotus, to investigate whether nocturnal and diurnal species of primates have similar cell classes. Monkey and cat ganglion cells from regions of matching cell class densities were also compared. Cat alpha, cat beta, Aotus M, and Cebus M cells were similar in many aspects, but Cebus M cells had higher branching density. Cebus and Aotus P cells formed a distinct group and represent a primate specialization common to diurnal and nocturnal simians.

Animals↗
PubMed1994

Loss of the compound action potential: an electrophysiological, biochemical and morphological study of early events in axonal degeneration in the C57BL/Ola mouse.

In the C57BL/Ola (Ola) mouse strain there is a marked slowing of axonal disintegration during Wallerian degeneration. The locus of the mutation controlling this phenomenon (slow Wallerian degeneration--Wlds) has been mapped to chromosome 4, and its protective effect decreases with advancing age. Using biochemical, electrophysiological and histological techniques, the present study was undertaken to determine whether neurofilament phosphorylation and stability are altered or whether calcium-activated proteases are absent in the sciatic nerves of Ola mice. A compound action potential was detectable only when neurofilaments were present and normal axonal architecture was seen. In 1-month-old Ola mice, compound action potentials and neurofilaments were still detectable at 21 days post-transection, whereas both were undetectable by 2 days in BALB/c and C57BL/6J (6J) mice of the same age. Neurofilament levels declined faster with advancing Ola age, confirming previous results, whereas degeneration slowed in ageing BALB/c and 6J mice. In vitro and in vivo degeneration rates were comparable in BALB/c and 6J nerves. Ola nerves, however, showed more rapid decline in vitro than in vivo. Ola and BALB/c nerves frozen and then thawed and incubated in the presence of calcium ions and the ionophore A23187 were not resistant to degradation by intrinsic proteases. Even when a compound action potential could no longer be elicited, however, a majority of nerves still had > 50% of myelinated and unmyelinated axons whose electron microscopic profiles appeared normal. Thus, it appears that the first event in Wallerian degeneration in the Ola mouse is a change at the plasma membrane--a transected nerve becomes unable to conduct a compound action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Further studies on motor and sensory nerve regeneration in mice with delayed Wallerian degeneration.

The axons of both peripheral and central neurons in C57BL/Wlds (C57BL/Ola) mice are unique among mammals in degenerating extremely slowly after axotomy. Motor and sensory axons attempting to regenerate are thus confronted with an intact distal nerve stump rather than axon- and myelin-free Schwann cell-filled endoneurial tubes. Surprisingly, however, motor axons in the sciatic nerve innervating the soleus muscle regenerate rapidly, and there is evidence that they may use Schwann cells associated with unmyelinated fibres as a pathway. If this is so, motor axon regeneration might be impaired in C57BL/Wlds mice in the phrenic nerve, which has very few unmyelinated fibres. We found that as long as the myelinated axons in the distal stump of the phrenic nerve remained intact (up to 10 days), regeneration of motor axons did not occur, in spite of vigorous production of sprouts at the crush site. In contrast to motor axons, myelinated sensory axons regenerate very poorly in C57BL/Wlds mice, even in the presence of unmyelinated axons. We showed that this was also due to adverse local conditions confronting nerve sprouts, for the dorsal root ganglion cell bodies responded normally to injury with a rapid induction of Jun protein-like immunoreactivity and when the saphenous nerve was forced to degenerate more rapidly by multiple crush lesions sensory axons regrew much more successfully. The findings show that motor and sensory axons in C57BL/Wlds mice, although very atypical in the way that they degenerate, are able to regenerate normally but only in an appropriate environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Motor neuron death induced by axotomy in neonatal mice occurs more slowly in a mutant strain in which Wallerian degeneration is very slow.

In contrast to motor neurons of adults, motor neurons of neonatal mice die if their axons are cut. We have examined the extent, the time course and the loss of susceptibility with age to such induced death in C57BL/Wlds mice. This is a strain which has a dominant autosomal mutation which dramatically slows the rate of degeneration of axons separated from their cell bodies. Following axotomy in neonatal animals the total number of motor neurons killed is no less in C57BL/Wlds mice than in two other strains (C57BL/6J/Ola and BALB/c/Ola). Indeed, the susceptibility to axotomy persists to a later age in C57BL/Wlds mice. However, the rate of cell death is significantly slower than in the two other strains; in C57BL/Wlds mice under a week old at the time of sciatic nerve section only approximately 16% of motor neurons have been lost 3 days after axotomy, whereas in the other mice approximately 45-84% of the final loss has by then occurred. This result extends previous work which showed that retrograde degeneration of retinal ganglion cells of adult mice was slower in C57BL/Wlds mice (V. H. Perry et al., Eur. J. Neurosci., 2, 408-413, 1991). It is therefore possible that Wallerian degeneration of axons shares features in common with retrograde nerve cell death and that the Wlds mutation may throw light on aspects of this complex process.

Aging↗
PubMed1994

Biology of the mononuclear phagocyte system of the central nervous system and HIV infection.

Infection of the central nervous system by HIV-1 results in widespread neuropathology and neurological symptoms. The cells infected in the brain belong to the mononuclear phagocyte lineage. We review aspects of the biology of the macrophage populations associated with the central nervous system and consider their distribution, phenotype, and kinetics in relation to HIV pathology.

Central Nervous System↗
PubMed1994

The ganglion cell response to optic nerve injury in the cat: differential responses revealed by neurofibrillar staining.

The early responses of cat retinal ganglion cells to axotomy have been examined using neurofibrillar and Nissl-stained wholemounts. We were interested to learn whether the enhanced neurofilament expression, seen in a number of neuronal systems, was also present in different neuronal populations of the cat retina and could be used to study the distribution of these cells. We found that beta ganglion cells degenerate very rapidly after axotomy with the nuclei becoming pyknotic within a few days. Few beta cells showed increased neurofibrillar staining of the dendrites. The cell body degenerated prior to any visible degenerative changes in the axon. A proportion of the alpha and gamma ganglion cells degenerated in the first two to three weeks after axotomy. The alpha cells underwent markedly enhanced neurofibrillar staining of their dendrites prior to degeneration. The Nissl material of the cell bodies diminished as the cells degenerated but we have not observed pyknotic nuclei. The dendritic trees of some axotomised gamma cells were also revealed by the neurofibrillar stain three weeks after axotomy. These results show that retinal ganglion cells do not degenerate by a dying back process. We suggest that the rapid degeneration of the beta ganglion cell population comes about by excitotoxic cell death, a consequence of their large glutamatergic input from bipolar cells. The degenerating beta ganglion cells have the morphological appearance of cells undergoing apoptosis.

Animals↗
PubMed1994

Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS.

The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.

Animals↗
PubMed1994

Quantification of the mononuclear phagocyte response to Wallerian degeneration of the optic nerve.

We investigated the numbers, origin and phenotype of mononuclear phagocytes (macrophages/microglia) responding to Wallerian degeneration of the mouse optic nerve in order to compare it with the response to Wallerian degeneration in the PNS, already described. We found macrophage/microglial numbers elevated nearly four fold in the distal segments of crushed optic nerves and their projection areas in the contralateral superior colliculus 1 week after unilateral optic nerve crush. This relative increase in mononuclear phagocyte numbers compared well with the four-to-five-fold increases reported in the distal segments of transected saphenous or sciatic nerves. Moreover, maximum numbers are reached at 3, 5 and 7 days in the saphenous, sciatic and optic nerves respectively, suggesting that the very slow clearance of axonal debris and myelin in CNS undergoing Wallerian degeneration is not simply due to a slow or small mononuclear phagocyte response. The apparent delay in the response in the CNS occurs because the mononuclear phagocytes respond to the Wallerian degeneration of axons, which is slightly slower in the CNS than the PNS, rather than to events associated with the crush itself, such as the abolition of normal electrical activity in the distal segment. This was demonstrated by the protracted time course of the mononuclear phagocyte response in the distal segment following optic nerve crush in mice carrying the Wlds mutation which dramatically slows the rate at which the axons undergo Wallerian degeneration. By [3H]-Thymidine labelling or by blocking microglial proliferation by X-irradiation of the head prior to optic nerve crush, we showed that the majority of macrophages/microglia initiating the response to Wallerian degeneration were of local, CNS origin but these cells rapidly (from 3 days post crush) upregulate endocytic and phagocytic functional markers although they do not resemble rounded myelin-phagocytosing macrophages observed in degenerating peripheral nerves. We speculate that the poor clearance of myelin in CNS fibre tracts undergoing Wallerian degeneration compared to the PNS, in the face of a mononuclear phagocyte response which is similar in relative magnitude and time course, is because Schwann cells in degenerating peripheral nerves promptly modify their myelin sheaths such that they can be recognized and phagocytosed by macrophages, whilst in the CNS oligodendrocytes do not.

Analysis of Variance↗
PubMed1994

Characterization of the microglial response in murine scrapie.

The nature of the glial and inflammatory cell responses to infection in scrapie-affected brains was studied in terminally-affected mice of five scrapie models. There were marked astrocytic and microglial responses. Microglia showed increased staining of the surface antigens F4/80, leucocyte-common antigen, type 3 complement receptor, and elevated endocytotic and lysosomal activity. In all models, the astrocytic and microglial responses were largely restricted to anatomical regions of the brain showing vacuolation and/or plaque formation and pathological accumulations of PrP. Expression of MHC Class II was patchy and present on microglia in the neuropil of areas with the most intense microglial activation and on occasional perivascular macrophages. This microglial response may represent a modified form of inflammatory response.

Animals↗
PubMed1994

MHC class II expression by microglia in tetanus toxin-induced experimental epilepsy in the rat.

Minute amounts of tetanus toxin injected into the hippocampus of rats results in an epileptiform syndrome. When the toxin injection is made unilaterally or bilaterally into the ventral hippocampus, about one-third of animals with seizures show bilateral neuronal loss in dorsal CA1 of the hippocampus after 1 week. In animals with seizures, microglia in hippocampus are found to be activated. The present work shows that during the acute phase, microglia in the substantia nigra become activated and express MHC class II antigens in the majority of animals with seizures. After the animals have recovered from the acute phase at 8 weeks, the MHC class II expression has largely disappeared from the substantia nigra but MHC class II-expressing microglia are found in the dorsal hippocampus of those rats with loss of cells from CA1. These results show that microglia are responsive to abnormal electrical activity in the central nervous system in the absence of degenerative changes. Further studies are required to determine how microglia may contribute to the neuropathology of epilepsy.

Animals↗
PubMed1993

A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4.

When a nerve axon is cut or crushed, the nerve fibers in the distal part of the axon, separated from the cell body, undergo a form of spontaneous degeneration, known as Wallerian degeneration. A substrain of the mouse inbred strain C57BL, known as C57BL/Ola, carries a mutant form of a gene involved in Wallerian degeneration in the peripheral and central nervous systems, and in retrograde degeneration of retinal ganglion cells. Wallerian degeneration in this substrain is abnormally slow. Previously the defect had been shown to be due to an autosomal dominant gene. The locus has been given the name and symbol Wallerian degeneration Wld, with the mutant allele Wlds (Wallerian degeneration-slow). The Wld locus has now been mapped, by using conventional and molecular markers, to the distal end of chromosome 4, near the locus of pronatriodilatin (Pnd). The order of loci (with recombination distances in centimorgans, cM) is cen-D4Mit11-8.9 +/- 1.7 cM-Fuca-2.5 +/- 0.93 cM-Akp-2-3.2 +/- 1.1 cM-D4Mit48-3.5 +/- 1.1 cM-(Wld, Pnd, D4Mit49)-0.71 +/- 0.50 cM-(Eno-1, D4Mit33)-1.4 +/- 0.70 cM-D4Mit42-2.5 +/- 0.93 cM-D4Smh6b. The information on the position of the Wld locus should be valuable in further characterization of this gene involved in nerve degeneration and regeneration.

Animals↗
PubMed1993

Altered antigen expression of microglia in the aged rodent CNS.

Microglia, the resident macrophages of the central nervous system, are characterised by a highly specialized morphology and unusual antigenic phenotype. Microglia appear to be downregulated by their microenvironment when compared to other tissue macrophages. We have studied the microglia in brains of healthy, aged rats with a panel of monoclonal antibodies. We have found that microglia in the brains of these aged rats express antigens that are downregulated or absent from microglia of juvenile rats. The stimuli which give rise to this upregulated phenotype are not known. Age related changes in the phenotype of microglia should be taken into account when considering the possible role of microglia in neuropathological conditions.

Aging↗
PubMed1993

Macrophages and inflammation in the central nervous system.

Acute inflammation plays an important role in host tissue defense against injury and infection, and also subsequent tissue repair. In the central nervous system parenchyma, following many types of insults, the acute inflammatory response to rapid neuronal degeneration or challenge with inflammatory substances differs dramatically from that of other tissues. The rapid recruitment of neutrophils is virtually absent and monocytes are only recruited after a delay of several days. It appears that the microenvironment of the central nervous system has evolved mechanisms to protect it from the potentially damaging consequences of some aspects of the acute inflammatory response.

Animals↗
PubMed1993

Microglial responses to physiological change: osmotic stress elevates DNA synthesis of neurohypophyseal microglia.

We were interested to discover whether microglia could play a role in the remodelling of the adult CNS or participate in adaptations to physiological rather than pathological changes. We have studied microglia in the neurohypophysis of adult mice since microglia normally interact with neurons in this tissue and the biochemical and anatomical consequences of osmotic stress on the neurohypophysis are well known. In this study, we have examined microglial immuno-phenotype and numbers synthesizing DNA in the neurohypophysis of adult mice to establish whether these cells respond to progressive osmotic stress. Neurohypophyseal F4/80+ microglia underwent a large synchronous burst of DNA synthesis 48 h after initiation of osmotic stress (drinking 2.5% saline). The labelling index (percentage of F4/80+ cells labelled by [3H]thymidine) 1 h after injection the isotope rose to 17% from a control value of less than 1%. On the third day of treatment the labelling index had returned to control levels. In contrast, non-microglia cells in the neurohypophysis and microglial cells elsewhere in the brain did not show this response. The increase in DNA synthesis was not accompanied by signs of microglia activation commonly observed in inflammatory models. They did not acquire an "activated" or "hypertrophic" morphology, nor was their staining with a panel of antibodies greatly altered. A small up-regulation of CD45 expression was the only phenotypic change detected. Thus, neurohypophyseal microglia respond to increased neurosecretory activity during the adaptation to osmotic stress in a distinctive way which differs from microglia reactions to inflammatory stimuli elsewhere in the CNS.

Adaptation, Physiological↗
PubMed1993

Mitosis and apoptosis of microglia in vivo induced by an anti-CR3 antibody which crosses the blood-brain barrier.

Microglia, the resident tissue macrophages of the central nervous system, have a highly differentiated morphology and do not express many of the antigens typically associated with other tissue macrophages. Activation of microglia is associated with a change in morphology and an increase in their repertoire of antigen expression. Microglia become activated in many neuropathological conditions including chronic neurodegenerative diseases and human immunodeficiency virus neuropathology, yet little is known of the mechanisms involved. Here we demonstrate for the first time that microglia can be activated and induced to divide and/or undergo apoptosis via a beta 2-integrin (complement receptor type 3, CR3, Mac-1 or CD11b/CD18) using an anti-CR3 monoclonal antibody (McAb5C6). This antibody, which has been shown to block myelomonocytic recruitment during central nervous system inflammation, is unique in that it can cross the intact blood-brain barrier to activate microglia. Since CR3 not only binds the iC3b component of the alternative complement cascade but also denatured proteins this suggests a potential route for microglia activation in neuropathological conditions.

Animals↗
PubMed1993

The M-ganglion cell density gradient in New World monkeys.

The M-ganglion cell distribution was studied in the retinae of New World monkeys, the diurnal Cebus and the nocturnal Aotus. Retinal whole mounts were stained by the neurofibrillar method of Gros-Schultze. The M-ganglion cell distribution in the Cebus and Aotus is similar to that reported for Old World primates, such as the Macaca. The M-ganglion cell density peak occurs in the foveal slope and declines towards the periphery. There is a nasotemporal asymmetry: in the Cebus retina the M-ganglion cell density is 1.2-4.3 times higher in the nasal when compared to the temporal region at the equivalent eccentricities; in the Aotus, the nasotemporal asymmetry is smaller, 1.6-2.2 higher in the nasal region. We compared the M-ganglion cell density with previously published values for the density of the total population of ganglion cells and observed a larger proportion of M-ganglion cells in the Aotus, when compared with Cebus or Macaca.

Animals↗