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P McConnell

Publications and source records attributed to P McConnell.

31 records · Page 2Linked to original sources
PubMed1983

Deposition of scar tissue in the central nervous system.

Standard parasagittal lesions were placed stereotactically in the cerebral hemispheres of neonatal and adult rats in order to compare scarring in the immature and mature animal. Lesions were examined by light and electron-microscopy and immunofluorescence to study the astrocyte reaction, collagen deposition, and the formation of the basement membrane of the glia limitans. Normal mature scarring characterized by the deposition of collagen, astrocyte end-feet alignment over a glia limitans, and the permanent presence of mesodermal cells (fibroblasts and macrophages) in the core of the lesion, does not occur in wounds before 8-10 days post-partum (dpp). Instead there is no deposition of collagen, and only a transitory astrocyte response occurs with the formation of an interrupted glia limitans. These latter features disappear with time so that the wound is ultimately obliterated by the growth of axons and dendrites through the lesion. Mature scarring is attained over 8-12 dpp when increasing amounts of collagen are deposited and a continuous permanent glia limitans is formed. The acquisition of the mature response to injury from 8-12 dpp may be correlated with the presence of increasing titres of a fibroblast growth factor (FGF), derived from autolytic digestion of injured brain tissue. We have investigated FGF activity using a 3 T 3 fibroblast tissue culture assay to detect mitogenic activity in brain extracts from rats lesioned at different ages and from leukodystrophic mice which have no myelin. Our results show that high titres of FGF are present in the developing brain long before myelination commences, and that normal levels of FGF are found in the brains of leukodystrophic mice which have no myelin. Scarring in brain lesions in these mutants is quite normal.

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PubMed1982

Regeneration of ganglion cell axons in the adult mouse retina.

The hypothesis that regenerative failure of axons in the adult mammalian CNS is due to release of a growth inhibitor from injured oligodendrocytes and/or myelin2, predicts that regeneration of injured fibers would proceed unchecked in unmyelinated CNS regions. This prediction was borne out by observations on the stratum opticarum of the mouse retina. Axonal sprouts, first seen 14-16 h post-lesion (pl), continued growing until at least 100 days pl, well beyond the time at which regeneration fails in myelinated CNS regions.

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PubMed1982

Regeneration of axons in the mouse retina after injury.

It is generally accepted that most axons in the mammalian CNS show only transient growth in response to injury, and numerous hypotheses have been advanced to account for this phenomenon. Detailed knowledge of the time-course and extent of this so-called 'abortive regeneration' is, however, surprisingly lacking. The retina of the adult albino mouse provides a convenient system in which to quantify the response of central axons to injury, since the retina can be prepared as a whole mount, allowing silver-impregnated axons to be followed along their entire course. Using this experimental model, sprouting of injured axons was observed as early as 14 h post lesion (hpl) with rapid growth (20 micrometers/day on average) continuing until 10 dpl. Thereafter, a decline in the overall growth rate was observed, presumably regenerated sprouts began to degenerate. However, not all axons showed this abortive response: numerous unfasciculated axons continued in random growth until at least 100 dpl. One possible interpretation of these results is that the concept of abortive regeneration of injured axons is untenable in regions of the CNS which are lacking in myelin.

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PubMed1981

The effects of refeeding after varying periods of neonatal undernutrition on the morphology of Purkinje cells in the cerebellum of the rat.

Undernutrition of the rat for the first 30 days of postnatal life is known to permanently alter Purkinje cell (PC) dendritic morphology. The effects of earlier nutritional rehabilitation have not previously been determined. Neonatal rat pups were undernourished by limiting their access to the lactating dam. After 10, 15, or 20 days of food restriction, animals were either killed for histological comparison with normally fed controls, or provided with ad libitum food until 80 dpp, and then killed. Network analysis of Golgi Cox impregnated PCs from the undernourished animals revealed alterations in dendritic length, segment frequency, and branching pattern, which first became apparent at 15 dpp, accompanied by a reduction in the number of granule cells (GCs) per PC. If undernourished animals were refed from 10 or 15 days, however, the total lengths and segment frequencies of their PC trees were indistinguishable from those of controls at 80 dpp, although the 15-day group showed persistent topological alterations. The GC:PC ratios of these refed groups were also found to be similar to those of the controls. In animals refed after 20 days of undernutrition, network size remained reduced, as did the GC:PC ratio. The different degrees of recovery of PC dendritic field parameters recorded in the refed animals could be related either to enhanced GC replication afforded by refeeding, or to the existence of intrinsic mechanisms which limit the growth capacity of the PC dendrites.

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PubMed1981

Sex differences in effects of environmental stimulation on brain weight of previously undernourished rats.

Neonatally undernourished male and female rats were housed under differential (enriched vs standard) environmental conditions during refeeding from 30 days post-partum (dpp). Animals were killed at 170 dpp and whole brain, forebrain and cerebellar weights compared with those of normally-fed, differentially housed control animals. A sex difference was observed in the response to environmental enrichment. Enriched females showed significantly increased brain weights, irrespective of previous nutritional history. Enriched males failed to show any significant alteration in brain weight. Autopsy results indicated that the enriched condition was stressful to males but not to females. The results cast doubt on the notion that infantile undernutrition may limit later effects of differential experience on the brain.

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PubMed1978

The effect of refeeding after neonatal starvation on Purkinje cell dendritic growth in the rat.

Male rats, undernourished from birth until 30 days by restricting access to the lactating dam, were given ad libitum food supplies unitl 80 days. Body weight, whole brain weight and cerebellar remained significantly lower in these animals than in normally fed controls. Significant deficits in the area of the molecular and granular layers persisted at 80 days, although there was some recovery during the refeeding period. At the same time granule and Purkinje cell density declined, suggesting that the areal recovery was due to the expansion of the interneuronal matrix. Granule cell numbers remained unchanged between 30 and 80 days. Network analysis of Golgi-Cox preparations indicated a 28% decrease in overall size of the Purkinje cell dendritic networks, due primarily to a deficit in segment frequency which remained unchanged throughout the rehabilitation period. Segment length did, however, show some recovery; distal segments from 80-day experimental networks were significantly longer than those of 30-day undernourished animals. The results of the topological analysis suggested that dendritic remodelling had taken place during the rehabilitation period. The failure to observe a complete recovery in the size and morphology of the dendritic network may be explained in terms of recent suggestions that dendritic development is influenced both by the metabolism of the neurons themselves, and by the number and density of adjacent afferent axons. It is suggested that refeeding from 30 days leads to the recovery of Purkinje cell metabolism, but is unable to restore the parallel fiber deficit.

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PubMed1978

The effects of undernutrition on Purkinje cell dendritic growth in the rat.

The effects of undernutrition on the developing cerebellum were studied in 30-day-old rats undernourished from birth by restricting access to the lactating mother. These animals showed a significant reduction in cerebellar weight when compared with well-nourished controls. Quantitative studies of the cerebellar vermis revealed a 34.2% reduction in total area, with the density of both granule cells and Purkinje cells increased. Network analysis of Golgi-Cox preparations indicated a significant increase in the density of dendritic fields of Purkinje cells, although there was a 37% decrease in overall network size, due to reduction in the total number of dendritic segments, and a reduction in the length of distal segments. Topological analysis indicated that the network had developed by terminal branching, as in normal animals, but with some deviation from the usual purely random branching pattern. All the observed modifications may be accounted for in terms of alterations in protein synthesis and DNA synthesis occurring in undernourished animals. This leads to alterations in the extent of the interneuronal matrix, a reduction in the number of granule cells and direct effects on Purkinje cell metabolism, all of which influence dendritic development, although the relative importance of each of these factors awaits precise definition.

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PubMedDate not supplied

Green tea extract and its polyphenols markedly inhibit luminol-dependent chemiluminescence activated by peroxynitrite or SIN-1.

This study is based on a simple chemical interaction of peroxynitrite (OONO-) and luminol, which produces blue light upon oxidation. Since peroxynitrite has a half-life of less than 1 s, a drug known as SIN-1 is used as a peroxynitrite generator. In addition peroxynitrite itself was used directly with a fast injection-mixing system to ascertain whether there are differences between it and the peroxynitrite-generating system (SIN-1) which mimics the natural production of (OONO-). Peroxynitrite is a potent oxidizing compound (1000 times more active than equidose hydrogen peroxide) and it can oxidize carbohydrates, lipids, proteins and nucleic acids. Upon stimulation by inflammation and/or infection, macrophages and neutrophils can be activated to produce large amounts of peroxynitrite. We are interested in simple chemicals that are non-toxic that could inhibit or destroy peroxynitrite, which might otherwise cause inappropriate damage to blood and tissues. Green tea is a complex mixture containing several potent major antioxidant constituents, eg flavins and/or polyphenols. The constituents in green tea may react directly or indirectly with peroxynitrite or its constituents through the process of antioxidation to inhibit light. Alternatively, compounds could produce superoxide which, when reacted with nitric oxide, could produce more peroxynitrite and hence more light with luminol. Therefore, as the tea or antioxidants from tea are diluted, while the peroxynitrite or its precursors are kept at a constant concentration, one can observe unusual behaviour regarding light emission. Initially, at high doses of tea or antioxidant, one observes clear inhibition of the light generated from the reaction of peroxynitrite and luminol. However, at dilute concentrations of antioxidants, one can often observe stimulation of light. Possible reasons for these observations are discussed.

Catechin↗
PubMedDate not supplied

The effects of postnatal lead exposure on Purkinje cell dendritic development in the rat.

Rat pups, suckled by mothers maintained after parturition on a diet containing 4% lead acetate, were killed at 30 days and their cerebella examined. The blood lead was greatly increased in these animals (258.20 +/- 6.72 micrograms/100 ml) as compared with controls (4.75 +/- 0.75 micrograms/100 ml) and their mean body weight was reduced by 28%. Cerebellar weight, however, remained unchanged. Histologically the vermis showed vacuolation of the white matter and an increase in the size of Purkinje cell bodies. The total number of Purkinje and granule cells and their densities were unchanged except in animals with encephalopathy when these parameters were reduced. Network analysis of the dendritic trees of Purkinje cells indicated a 34.8% reduction in total dendritic length, due to reduction in total segment number and in the length of distal segments. Dendritic density and the frequency of trichotomous branching were unchanged by the experimental treatment. The density of dendritic spines over the periphery of the network was normal. The topology of the dendritic trees of Purkinje cells was abnormal in that branching patterns deviated from the normal pattern generated by random terminal growth. These results suggest that lead causes changes in Purkinje cell metabolism which reduce the rate of dendritic growth and cause abnormal branching. It remains to be determined whether these are direct effects or secondary to the vascular changes known to occur in the cerebellum during lead intoxication.

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