Biomedical subjects

Mark J West

Publications and source records attributed to Mark J West.

8 recordsLinked to original sources

PubMed2005

Electroconvulsive seizures induce angiogenesis in adult rat hippocampus.

BACKGROUND: Electroconvulsive seizure (ECS)-treatment, a model for electroconvulsive therapy (ECT) has been shown to induce proliferation of endothelial cells in the dentate gyrus (DG) of adult rats. Here we quantified the net angiogenic response after chronic ECS-treatment in the molecular layer (ML) of the dentate gyrus. Patients undergoing ECT are routinely oxygenated to prevent hypoxia, a known inducer of angiogenesis. Therefore we also examined the effect of oxygenation on ECS-induced proliferation of endothelial cells. METHODS: Total endothelial cell numbers and vessel length were estimated utilizing design based stereological analysis methods. Endothelial cell proliferation in the DG after ECS with or without oxygenation was assessed using bromodeoxyuridine. RESULTS: The total number of endothelial cells and total vessel length was increased. Oxygenation did not abolish the ECS-induced proliferation of endothelial cells in the DG. CONCLUSIONS: ECS-treatment induces a dramatic increase in endothelial cell proliferation leading to a 30% increase in the total number of endothelial cells. The increase in cell number resulted in a 16% increase in vessel length. These findings raise the possibility that similar vascular growth is induced by clinically administered ECT.

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PubMed2004

The anatomy of the porcine subthalamic nucleus evaluated with immunohistochemistry and design-based stereology.

This study provides a light-microscopic description of the organization, morphology and number of neurons in the subthalamic nucleus (STN) of the Göttingen minipig. It is based on histological material stained with Nissl, Golgi and autometallographic techniques, and employs design-based stereological estimation of the total neuron number. The organization of several neurotransmitters in the STN has been evaluated in histological preparations stained for acetylcholinesterase (AChE) and immunostained for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and glutamate. In all of the stained preparations the STN appeared as a distinct lens-shaped structure located in the caudal diencephalon, medial to the internal capsule and ventrolateral to the zona incerta. Rostrally, the STN approached the globus pallidus pars interna, whereas caudally the ventromedial part of the STN was adjacent to the rostral part of the substantia nigra pars compacta (SNc), where some of the neurons of the two nuclei merged. The neurons in the STN had medium-sized (25-40 microm) ovoid or fusiform cell bodies, from which three to six large dendrites emanated in a direction predominantly parallel to the long axis of the STN. Immunohistochemistry revealed that most of the subthalamic neurons were glutamatergic and differed significantly in appearance from the large stellate TH-positive cells of the adjacent SNc. Numerous TH-positive bouton-rich fibers traversed the STN. The GAD-staining revealed a large number of terminals within the boundaries of the STN. The STN was highly AChE-positive, reflecting a prominent innervation by ChAT-positive terminals. The total number of subthalamic neurons in one hemisphere was estimated to be approximately 56,000. We conclude that the neuroarchitecture of the porcine STN is similar to primates, including humans, and appears well-suited for further studies examining the role of the STN in movement disorders.

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PubMed2004

NDRG2: a novel Alzheimer's disease associated protein.

Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the alpha/beta-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD.

Adolescent↗

PubMed2004

Hippocampal neurons in pre-clinical Alzheimer's disease.

In a previous study of hippocampal neurons in aging and AD [Lancet 344 (1994) 769], we demonstrated that the loss of neurons in the CA1 region was disease-specific and not related to aging. In the present study, we examined for loss of hippocampal neurons in preclinical AD, a period during which there are abundant amyloid deposits in the brain but no evidence of cognitive decline. We examined the postmortem brains of 33 subjects from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Alzheimer's Disease Research Center. Using unbiased stereology, we estimated the total number of neurons in the granule cell layer, hilus, CA3-2, CA1, and subiculum of AD (n = 14) preclinical AD (n = 8), and age-matched control subjects (n = 11). The results from the present study confirm our previous finding of significant neuronal losses in the CA1 (48%), hilus (14%), and subiculum (24%) in AD [Lancet 344 (1994) 769]. However, we did not observe a significant loss of neurons in CA1 or any of the other subdivisions of the hippocampus in preclinical AD.

Aged↗

PubMed2002

Bismuth-induced neuronal cell death in rat dorsal root ganglion: a stereological study.

The goal of the present study has been to quantify the morphological changes in myelinated nerve roots and dorsal root ganglion (DRG) cells in rats exposed to bismuth subnitrate. Male Wistar rats (n =30) were divided into three groups of ten animals. The ten animals in each group were given intraperitoneal injections of one of the following: (1) 500 mg/kg bismuth subnitrate, (2) 1,000 mg/kg bismuth subnitrate, or (3) saline. The mean total cell number of B-cells in the DRG was significantly smaller in the two treated groups, 18% (2P <0.001) and 23% (2P <0.001), respectively, than it was in the control group. In addition, there was an 11% reduction in the number of A-cells (2P =0.039) in rats exposed to the highest concentration of bismuth. Bismuth did not affect the total number or mean cross sectional area of axons and myelin sheaths of the myelinated nerve fibers in the ventral or dorsal nerve root of the DRG. This is the first study to investigate pathological changes of the peripheral nervous system after bismuth intoxication.

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PubMed2002

Design-based stereological methods for counting neurons.

Recently developed stereological methods for counting neurons have a number of advantages over previously available stereological methods. These methods are most aptly referred to as 'design-based' because, in contrast to their predecessors, the probes and the sampling schemes that define the newer methods are 'designed', that is, defined a priori, in such a manner that one need not take into consideration the size, shape, orientation, and distribution of the objects to be counted. The elimination of the need for information about the geometry of the objects to be counted results in more robust data regarding estimates of total neuron number and neuronal loss because potential sources of systematic errors in the calculations are eliminated. In this article I will describe the salient features of the newer, design-based, methods and why they represent improvements over previously available methods.

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PubMedDate not supplied

Influence of bismuth on the number of neurons in cerebellum and hippocampus of normal and hypoxia-exposed mouse brain: a stereological study.

The industrial use of bismuth is increasing. In medicine, bismuth compounds have long been used in the treatment of gastrointestinal disorders, recently in combination with antibiotics for the treatment of Helicobacter pylori-associated peptic ulcers. Bismuth-induced encephalopathy is a known side-effect. One of the symptoms of bismuth encephalopathy is ataxia, suggesting possible cerebellar involvement. The introduction of autometallography (AMG) for tracing BiS/BiSe nanocrystals has provided histochemical evidence supporting the cerebellum being involved in bismuth encephalopathy, but the effect of bismuth on the neuron number in the cerebellum has never been evaluated. In vitro studies have indicated that CA1 neurons may be targets for bismuth intoxication, but results have been conflicting. Recently, the loss of dorsal root ganglion cells was reported after moderate bismuth exposure. This raises the question whether the use of another neurotoxic stimulus, such as hypoxia, amplifies the toxic effects of bismuth. Despite AMG-detectable bismuth accumulations, stereological examinations revealed no statistically significant decrease in the number of Purkinje, CA1 or CA3 neurons or in the volume of the cerebellar granule layer. Surprisingly, intermittent hypoxia led to a statistically significant loss of Purkinje cells without affecting the hippocampus. Bismuth neither ameliorated nor exacerbated the hypoxic effects on the cerebellum.

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PubMedDate not supplied

Leydig cell death in rats exposed to bismuth subnitrate.

In a previous study, rats were treated with one injection of 500 mg kg(-1) bismuth subnitrate intraperitoneally and maintained for 2 weeks. Bismuth was observed in Leydig cells, with a subsequent reduction in serum testosterone levels. In the present study, stereological procedures were used to estimate the number of Leydig cells in the right testis from the retained rats used in the previously published study. The mean number of Leydig cells in the control group was estimated to be 18.7 x 10(6) (coefficient of variation = 0.11), which is comparable to previous estimations. In the group exposed to bismuth the mean was 15.5 x 10(6) (coefficient of variation = 0.18). The observed 17% difference between the two groups was statistically significant (2P = 0.019). The inter-individual variation was largest in the bismuth-exposed group. Testis weight and body weight were not significantly reduced after bismuth exposure. These findings support the hypothesis that bismuth has a direct toxic effect on rat Leydig cells and underscores the potential risks of bismuth on male reproduction.

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