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V H Perry

Publications and source records attributed to V H Perry.

205 records · Page 12Linked to original sources
PubMedDate not supplied

Unusual aspects of inflammation in the nervous system: Wallerian degeneration.

Wallerian degeneration in the PNS is accompanied by the rapid recruitment of monocytes, but monocytes do not invade CNS fibre tracts undergoing Wallerian degeneration. In recent years it has become apparent that the acute inflammatory response to cell degeneration in the CNS is unlike that in other tissues. We have been interested to learn why Wallerian degeneration does not provoke a typical inflammatory response. We investigated whether the vascular endothelial cells express adhesion molecules during Wallerian degeneration in PNS and CNS. We found that in the degenerating sciatic nerve there was upregulation of ICAM-1 and VCAM-1 expression on endothelial cells in the distal stump of the injured nerve as well as at the site of the lesion. However, in the degenerating optic nerve, the endothelium failed to upregulated these molecules in the distal stump of the nerve and ICAM-1 expression was only increased in the crush site. The lack of adhesion molecule expression on CNS endothelium molecules may be an explanation for the poor leukocyte recruitment during Wallerian degeneration in CNS when compared with PNS.

Animals↗
PubMedDate not supplied

CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown.

Children are at greater risk than adults of permanent brain damage and mortality following head injury or infection [1-5]. Rodent models have demonstrated a 'window of susceptibility' in young animals during which the brain parenchyma is at greater risk of acute neutrophil-mediated breakdown of the blood-brain barrier [6-7]. The exact mechanism of this age-related susceptibility to brain inflammation has yet to be defined, but animal models have revealed that the potent pro-inflammatory cytokine interleukin-1beta (IL-1beta) initiates an intense acute neutrophil-mediated inflammatory response in the brains of young rats and mice that is not seen in adults [6]. Here, we demonstrate the rapid induction of CXC chemokines (which contain a Cys-X-Cys motif), in particular the cytokine-induced neutrophil chemoattractant CINC-1, following the intracerebral administration of IL-1beta. The CXC chemokines produced a more intense neutrophil response in young rats than in adults. The IL-1beta-induced blood-brain barrier breakdown in young rats could be attenuated by an anti-CINC-1 neutralising antibody. These results show that the immature central nervous system (CNS) is dramatically more susceptible to the chemotactic effects of CXC chemokines. Blocking the CXC chemokine activity associated with brain inflammation inhibits neutrophil-mediated blood-brain barrier damage and represents a significant therapeutic possibility.

Adult↗
PubMedDate not supplied

The retinal ganglion cell distribution and the representation of the visual field in area 17 of the owl monkey, Aotus trivirgatus.

The distribution of ganglion cells and displaced amacrine cells was determined in whole-mounted Aotus retinae. In contrast to diurnal simians, Aotus has only a rudimentary fovea. Ganglion cell density decreases towards the periphery at approximately the same rate along all meridians, but is 1.2-1.8 times higher in the nasal periphery when compared to temporal region at the same eccentricities. The total number of ganglion cells varied from 421,500 to 508,700. Ganglion cell density peaked at 15,000/mm2 at 0.25 mm dorsal to the fovea. The displaced amacrine cells have a shallow density gradient, their peak density in the central region is about 1500-2000/mm2 and their total number varied from 315,900 to 482,800. Comparison between ganglion cell density and areal cortical magnification factor for the primary visual cortex, area 17, shows that there is not a simple proportional representation of the ganglion cell distribution. There is an overrepresentation of the central 10 deg of the visual field in the visual cortex. The present results for Aotus and the results of a similar analysis of data from other primates indicate that the overrepresentation of the central visual field is a general feature of the visual system of primates.

Animals↗
PubMedDate not supplied

Morphology, dendritic field size, somal size, density, and coverage of M and P retinal ganglion cells of dichromatic Cebus monkeys.

Male Cebus monkeys are all dichromats, but about two thirds of the females are trichromats. M and P retinal ganglion cells were studied in the male Cebus monkey to investigate the relationship of their morphology to retinal eccentricity. Retinal ganglion cells were retrogradely labeled after optic nerve deposits of biocytin to reveal their entire dendritic tree. Cebus M and P ganglion cell morphology revealed by biocytin retrograde filling is similar to that described for macaque and human M and P ganglion cells obtained by in vitro intracellular injection of HRP and neurobiotin. We measured 264 and 441 M and P ganglion cells, respectively. M ganglion cells have larger dendritic field and cell body size than P ganglion cells at any comparable temporal or nasal eccentricity. Dendritic trees of both M and P ganglion cells are smaller in the nasal than in the temporal region at eccentricities greater than 5 mm and 2 mm for M and P ganglion cells, respectively. The depth of terminal dendrites allows identification of both inner and outer subclasses of M and P ganglion cells. The difference in dendritic tree size between inner and outer cells is small or absent. Comparison between Cebus and Macaca shows that M and P ganglion cells have similar sizes in the central retinal region. The results support the view that M and P pathways are similarly organized in diurnal dichromat and trichromat primates.

Animals↗
PubMedDate not supplied

[The evidence for primary axonal loss in multiple sclerosis].

INTRODUCTION: At what stage in the pathogenesis of multiple sclerosis (MS) does the damage to axons occur, and why should there be any axon loss at all in what is thought to be principally an axon sparing demyelinating disease? A recently described new technique for investigating axon damage depends for its ability on the immunoreactivity of amiloid precursor protein (APP), which has been shown to be more sensitive than silver stains for detecting damaged axons. DEVELOPMENT: We used APP immunoreactivity as a method to investigate whether axon damage occurs in acute MS lesions. The results of our APP staining showed that the expression of APP in MS lesions is associated with acute MS lesions and the active border of less acute lesions. There was little, if any, APP expression in the chronic lesions. If we accept that the APP staining represents irreversible damage to some axons, the next question is what factors are responsible for mediating damage to axons in MS? Matrix metalloproteinases (MMP) are expressed by macrophages in acute MS lesions and in the active borders of active chronic lesions. The injection of highly-purified MMP into the brain results in demyelination, blood-brain barrier breakdown, and axonal loss. Moreover, the inhibition of the MMP activity reduces the severity of MS-like lesions in experimental models. Thus the properties and distribution of these enzymes make them rational targets for therapeutic intervention. CONCLUSION: Whatever mechanism proves to be responsible for axonal damage in MS, it is clear that this disease should, perhaps, be more appropriately recognized as a primary demyelinating entity with associated primary axonal loss.

Acute Disease↗