Magnitude Of Cell Loss Research Articles

TOTAL NUMBER: A BRIEF REVIEW OF ITS IMPORTANCE AND ITS USE IN ASSESSING CEREBELLAR DAMAGE IN THE RAT FOLLOWING EARLY POSTNATAL ALCOHOL EXPOSURE

Knowledge of the total number of structural components that make up the various neural networks within the central nervous system is fundamental to our understanding of its normal function and of dysfunction that may accompany injury and disease. This paper briefly reviews the methodology currently used to estimate number and discusses the importance of unbiased estimates of total number in determining changes in brain structure that may underlie dysfunction. An example from the olfactory bulb is used to demonstrate the potential invalidity of using estimates of total number of objects per single section. Exposure to alcohol during the early postnatal period results in motor dysfunction in adult rats. This paper presents data on the extent and magnitude of cell loss within the cerebellar network of the rat following alcohol exposure during postnatal days 4 to 9. High transient blood alcohol concentrations result in a Purkinje cell of 27% across the entire cerebellum but with regional variabiltiy, vermal lobule X has a 43% Purkinje cell deficit. This alcohol regimen also results in a neuronal loss of 28% and 25% within the deep cerebellar nucleus and inferior olivary nucleus respectively. Consistency of overall neuronal loss across diverse neuronal populations within the cerebellar network is discussed in the context of the maintenance of cerebellar connectivity.

Behavioural effects of trishomocubanes in rats with unilateral 6-hydroxydopamine lesions

Whilst dopamine replacement improves cardinal features of Parkinson's disease, chronic levodopa administration is associated with dose-related side effects and not all symptoms are ameliorated, necessitating the development of new treatments. Studies of trishomocubanes, a novel group of sigma ligands, have shown enhanced amphetamine-stimulated striatal release of dopamine and a potentially neuroprotective action in vitro and reversal of reserpine-induced catalepsy in vivo. Such effects warrant investigation in animal models of parkinsonism. Our study therefore examines two novel trishomocubane compounds, N-(3′-fluorophenyl)methyl-4-azahexacyclo[5.4.1.0 2,6.0 3,10.0 5,9.0 8,11]dodecan-3-ol ( 1) and, N-(3′-fluorophenyl)ethyl-4-azahexacyclo[5.4.1.0 2,6.0 3,10.0 5,9.0 8,11]dodecan-3-ol ( 2) in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. A variety of motor behaviours were studied in rats given 6-OHDA lesions. Groups of lesioned rats were given either ( 1) or ( 2) or vehicle solution i.p. Acute administration of 3 mg/kg ( 1) resulted in a decrease in locomotor activity. Twenty-five milligrams per kilogram ( 2) caused a decrease in locomotor activity at t = 10 and t = 20 min of the locomotor test but this was not found when ( 2) was co-administered with either apomorphine or amphetamine. The decreased locomotor activity indicates that ( 1) and ( 2) may have sedative/anxiolytic effect(s). However, elevated plus maze data failed to demonstrate anxiolysis with ( 2). Quantification of dopaminergic neurons did not demonstrate any significant difference in the magnitude of cell loss between drug-treated vs. vehicle treated rats so no neuroprotective effect was demonstrated in this model at the doses utilised.

A simple method to measure stride length as an index of nigrostriatal dysfunction in mice

Reduced stride length characterizes Parkinsonian gait. We aimed to demonstrate that it could be measured simply and reliably in mice by pawprints and used as an index of basal ganglia dysfunction. In C57BL/6 mice, stride length measurements proved to be consistent across measurements and experimenters. It was slightly lower in the hindlimbs and was correlated to femur size and animal velocity. Dopamine depletion by reserpine and striatal dopamine receptor blockade by haloperidol resulted in reduced mean stride length in four limbs. Significant forelimb/hindlimb difference was also observed both in mice with 3-nitropropionic acid (3-NP) induced striatal lesions and in those with MPTP-induced nigral cell loss. Reduction of hindlimb stride length was correlated significantly with the magnitude of cell loss, either in the substantia nigra or in the lateral mid-striatum. Stride length is, therefore, a simple method to obtain an index of motor disorders due to basal ganglia dysfunction in mice.

Evidence for Degeneration of Retinal W Cells following Early Visual Cortical Removal in Cats

Size and distribution of ganglion cells surviving unilateral visual cortical removal at 5-7 days of age were examined in domestic cats. Such lesions were expected to result in a substantial loss of X cells in ipsilateral temporal and contralateral nasal retina, leaving ipsilateral nasal and contralateral temporal retina to serve as intact controls. A computer model of normal retinal ganglion cell topography was used to make qualitative predictions of the distribution of surviving ganglion cells. Contrary to expectations, a visual streak was no more prominent in the distribution of surviving cells than in the distribution of the normal ganglion cell population. The magnitude of ganglion cell loss, furthermore, was at least twice as great in nasal retina as in temporal retina. In nasal retina, the cell loss extended well into the small-medium size range, while in temporal retina, cell loss was restricted to the large-medium size range. Taken together, the differential magnitude of cell loss in nasal and temporal retina and the greater loss of small-medium cells in nasal retina cannot be explained by the exclusive degeneration of X cells and suggest that many of the degenerated ganglion cells were medium-sized W or gamma cells. These cells, therefore, share the susceptibility of retinal X cells to early cortical ablation. Surviving gamma cells in both nasal and temporal retina appeared to increase in soma size which may explain why their decreased numbers were not detected in previous physiological studies. Alpha cells, at least in nasal retina, decreased in some size.

MPTP-induced ventral mesencephalic cell loss in the cat

Immunohistochemical analysis of tyrosine hydroxylase (TH)-containing neurons in the cat ventral mesencephalon revealed a marked loss of substantia nigra pars compacta neurons and moderate losses of TH-positive neurons in the ventral tegmental area, retrorubral or A 8 region, and in the substantia nigra pars lateralis of cats treated with the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The pattern and magnitude of cell loss in these ventral mesencephalic regions parallels that previously reported for the MPTP-treated monkey. These results further support the use of the cat as a model for studying the pathology to catecholaminergic neurons induced by MPTP.

Developmental neuron cell death in dystrophic and normal chickens

The numbers of motoneurons in the brachial lateral motor columns were determined from the 6th embryonic day through the 5th week posthatching in age-matched dystrophic and normal chickens. The overall magnitude of cell loss was not significantly different between the dystrophic and normal strains. However there was a trend toward more motoneurons in the brachial lateral motor columns of dystrophic embryos and posthatch chickens which was found to be statistically significant at the 8th and 9th days of embryonic life. These observations are taken to suggest that, in addition to strain differences unrelated to the dystrophic gene, there may exist a temporal delay in developmental neuron cell death in dystrophic chick embryos that may be secondary to the primary defect within the dystrophic muscle.

An experimental study of cell death in the developing trochlear nucleus

The development of the trochlear nucleus in the absence of its peripheral field of innervation was studied, from Day 7 of incubation age through hatching, in duck embryos ( Anas platyrhynchos). The optic primordium and the surrounding mesoderm were removed, usually on the right side, on the fourth day of incubation. Data on cell number and size on Day 12, when the nucleus attains maximum number of cells, indicate no significant differences between the control and the affected nucleus. Removal of the superior oblique muscle thus has no effect on proliferation and differentiation of the cells till Day 12. There is, however, a 50% cell loss in the control nucleus between Days 13 and 21. An additional hypoplasia in the affected nucleus is observed from Day 13 to hatching. Magnitude of cell loss in the affected nucleus varies from 85% loss to a virtual absence of the cells at hatching. Two morphologically distinct cell types, e.g., large well-differentiated, and small relatively undifferentiated cells are present in the control and the affected trochlear nucleus during the early period of morphogenesis. Cell death in the control is limited to the small cell population. It is suggested that the normally occurring cell death involves those cells (small cells) unable to send axons to the periphery to make connections. The additional hypoplasia in the affected nucleus is probably due to the failure of the growing axons to make appropriate synaptic contacts with the periphery.