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Biomedical subjects

H Pollard

Publications and source records attributed to H Pollard.

At least 37 records · Page 2Linked to original sources
PubMed1994

Determination of cardiac output using acoustic quantification in critically ill patients.

The reliability of automated acoustic quantification (AQ) in yielding real-time left ventricular (LV) area, volume, and ejection fraction has been validated. The purpose of this study was to explore the potential of AQ in providing accurate immediate determination of cardiac output in critically ill patients. A total of 48 patients were studied. One group consisted of 37 critically ill patients with indwelling Swan-Ganz catheters. In these patients, cardiac output by AQ, manual tracing of end-diastolic and end-systolic frames of 2-dimensional images, and thermodilution were measured. AQ was also compared with Doppler calculation of flow through the left and right ventricles in 11 additional patients. Adequate data for calculation of cardiac output with AQ were obtained in 78% of critically ill patients. There was an excellent correlation between AQ and off-line manual analysis for LV volumes (r = 0.94 and 0.91 for end-diastole and end-systole), ejection fraction (r = 0.85), and cardiac output (r = 0.93). AQ also correlated well with Doppler analysis (r = 0.97) and thermodilution technique (r = 0.95) in the determination of cardiac output. However, AQ slightly underestimated thermodilution measurements, with rather wide limits of agreement (-0.3 +/- 1.1 liter/min). There was a similar underestimation of cardiac output with manual analysis when compared with thermodilution. Given the absence of significant differences between AQ and manual analysis, this observation suggests that the bias is related to the echocardiographic determination of stroke volume, and not to errors from the automated border detection. It is concluded that AQ, besides providing information on LV volumes and ejection fraction, also can yield rapid measurements of cardiac output in most patients who are acutely ill.

Acoustics↗
PubMed1994

Developmental change of alpha-spectrin mRNA in the rat brain.

Spectrin is a cytoskeletal protein considered to be a major component of intracellular cohesion. Using an in situ hybridization approach, we have investigated the developmental expression of the mRNA encoding the alpha-subunit of rat brain spectrins, from birth to adulthood. alpha-Subunit mRNA is detectable at birth, in brain areas with perinatal neurogenesis, such as the cerebral cortex, hippocampus, thalamus, and olfactory bulb. alpha-Brain-spectrin mRNA increases gradually during the first postnatal days to reach a plateau between the second and the third week of life. In the young adult brain, the level of alpha-brain spectrin mRNA decreased globally. This spacio-temporal distribution argues for the involvement of the mRNA in the synthesis of both the erythroid and non-erythroid brain spectrin isoforms. We have focused our attention on the hippocampal formation and the cerebellum. In both regions, in situ hybridization signal variations are superimposable with neuronal maturation gradients. This pattern of variation, coupled with the known interaction of brain spectrins with other cytoskeletal proteins, agrees with the notion that brain spectrins may be involved in neuronal differentiation by way of the cytoskeletal lattice organization.

Animals↗
PubMed1994

Use of hippocampal slices to study mRNA changes in relation to synaptic plasticity.

We have developed a method allowing suitable morphological conservation combined with in situ hybridization, on hippocampal slices used in conventional electrophysiological studies. After a bath application of kainate (KA, 750 nM, 2 min 15 s), electrical stimulation of the mossy fibre zone evoked epileptiform activity for up to 2 h. In situ hybridization performed on these slices showed a marked increased in expression of the transcription factor Zif/268 over the pyramidal and the granule cells and the surrounding neuropils. Bath application of tetraethylammonium (TEA, 25 mM, 10 min) elicited long-term potentiation in CA1 lasting up to 4 h. This was associated with enhanced expression of Zif/268 which returned to control values after 2 h 30 min. These observations suggest that slice preparations are suitable for the study of the role of neuronal activity in the regulation of gene expression.

Animals↗
PubMed1994

Apoptosis associated DNA fragmentation in epileptic brain damage.

We have examined the epileptic brain damage generated by intra-amygdaloid administration of kainic acid (KA). In the vulnerable CA3 region of the rat hippocampus, neurones developed apoptotic properties since, (i) their nuclei were positively stained with a selective in situ DNA fragmentation staining method; (ii) DNA cleavage into internucleosome-sized fragments was observed on agarose gels. Our results suggest that epileptic seizures generated in the amygdala by KA trigger apoptotic cell damage in pyramidal CA3 neurones.

Amygdala↗
PubMed1994

aFGF, bFGF and flg mRNAs show distinct patterns of induction in the hippocampus following kainate-induced seizures.

We report that kainic acid-induced seizures lead to marked increases in mRNAs encoding basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) and flg, one of their receptors, in the rat hippocampus. Anticonvulsant pretreatment inhibits the up-regulation of these mRNAs. The observed increase in flg mRNA levels involves the pyramidal cells of all hippocampal subfields and the granular cells of the dentate gyrus. The increased expression of aFGF and bFGF mRNAs is limited to neuron populations that are resistant to seizure-induced injury, the granular cells of dentate gyrus and pyramidal cells of CA1 region, respectively. The results suggest that the increase in the FGFs and flg may play pivotal roles in neuron survival and in long-term changes occurring in the hippocampus following seizure activity.

Animals↗
PubMed1994

Kainate-induced apoptotic cell death in hippocampal neurons.

We have examined the role apoptosis plays in epileptic brain damage using intra-amygdaloid injection of kainate. With the silver staining technique of Gallyas, argyrophylic (dying) neurons were observed, a few hours after the injection, in the amygdala and in the vulnerable pyramidal neurons of the hippocampal CA3 region. In both areas, cell death has apoptotic features, including: (i) nuclear chromatin condensation and marginalization with light and electron microscopy; (ii) DNA fragmentation with a typical ladder pattern on agarose gel electrophoresis; (iii) positive nuclear labelling with a selective in situ DNA fragmentation staining method. Combined in situ DNA labelling and silver staining showed that the DNA fragmentation occurred in dying neurons. CA1 or granule cells which do not degenerate following intra-amygdaloid injection of kainate were not stained with the in situ DNA labelling or the argyrophylic technique. Administration of diazepam blocked the kainate-induced seizures and prevented DNA fragmentation in CA3 but not in the amygdala. Therefore, apoptosis contributes to the local and distant damage induced by kainate.

Animals↗
PubMed1994

Correlation between reactive sprouting and microtubule protein expression in epileptic hippocampus.

Temporal lobe epilepsy in both human and rats is associated with a collateral sprouting of hippocampal mossy fibers (i.e. the axons of granule cells). This sprouting generates abnormal recurrent synaptic connections. We previously showed that in the experimental model of temporal lobe epilepsy induced by an intra-amygdaloid injection of kainate, the synaptic remodeling of mossy fibers was preceded by a transient increased expression of alpha-tubulin in granule cells. This suggests that an overproduction of tubulin polymers may be responsible, at least in part, for the elongation and side-branching of mossy fibers, which occurs 12-30 days after seizures. In the present study we show that this increased expression of alpha-tubulin is accompanied by an increased expression of the microtubule-associated proteins MAP2 and TAU. Thus, using in situ hybridization, we observe that MAP2 messenger RNA levels increased in granule cell bodies and dendrites from day 3 to two weeks after kainate treatment. This rise is associated with a concomitant transient increase of MAP2 immunoreactivity in the granule cell dendrites. TAU messenger RNA also increases in granule cell bodies, while TAU immunoreactivity increases in their axons, the mossy fibers. The time course of these changes parallels that of alpha-tubulin, and develops before and during the axonal mossy fiber sprouting. Since MAP2 and TAU are important for the initiation, elongation and stabilization of neurites, we suggest that the overexpression of these proteins via the formation of microtubules may play an important role in the sprouting of mossy fibers in epileptic rats.

Amygdala↗
PubMed1994

Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3.

Several human inherited diseases have been localized to the Xq13.3 region of the human X chromosome (X-linked dystonia with Parkinsonism, sideroblastic anemia, SCID, Menkes disease and X-linked mental retardation loci). Genes involved in the phenotypes have been isolated for only two of them (Menkes and SCIDX). It was therefore interesting to isolate and characterize new genes from the region. In a previous work (12 and Consalez et al, in preparation) we isolated a gene (XNP), located 350 Kb proximal to PGK1, potentially coding for a nuclear protein. We describe here the cloning and characterization of the murine homologue. The pattern of expression of the gene in the newborn mouse (especially the expression in particular regions of the brain: optical lobe, frontal cortex, hippocampus and cerebellum), as well as the expression in human tissues, suggests that this gene might be involved in neuronal differentiation. Among the different morbid phenotypes assigned to the region, X-linked mental retardation would be the best candidate to be associated with this gene.

Amino Acid Sequence↗
PubMed1993

Mossy fiber sprouting in epileptic rats is associated with a transient increased expression of alpha-tubulin.

Kainate-induced seizures lead to marked increases of alpha-tubulin mRNA and protein immunoreactivity in the rat dentate gyrus. The increase in alpha-tubulin mRNA was restricted to the granule cell bodies. alpha-Tubulin immunoreactivity was enhanced in granule cell dendrites and axons (the mossy fibers), in the molecular layer. These changes peaked 6-12 days after kainate treatment and preceded the collateral sprouting of mossy fibers which occur 12 to 30 days after seizures. The present results suggest that microtubule formation contributes to the synaptic rearrangements which take place in the hippocampus after seizures.

Amygdala↗
PubMed1993

Involvement of GABAA receptors in the outgrowth of cultured hippocampal neurons.

Whereas GABA is a major inhibitory neurotransmitter in the adult central nervous system, recent experiments performed in our laboratory have shown that the activation of GABAA receptors in the hippocampus leads to excitatory effects during the early post-natal period. The possible consequence of a depolarizing effect of GABA was assessed on the neuritic outgrowth of embryonic hippocampal neurons in culture. No morphological alterations were observed when hippocampal neurons were cultured for three days in the presence of muscimol, a GABAA receptor agonist. In contrast, the neuritic outgrowth of cultured hippocampal neurons was profoundly affected by the presence of bicuculline in the culture medium. In the presence of this GABAA receptor antagonist neurons displayed a reduction in the number of primary neurites and branching points, resulting in a concomitant decrease of the total neuritic length. Thus, this study suggests that GABA, acting on GABAA subtype of receptors, is able to affect the development of the hippocampus.

Animals↗
PubMed1993

Loss of striatal histamine H2 receptors in Huntington's chorea but not in Parkinson's disease: comparison with animal models.

Autoradiographic techniques were used to study the distribution of histamine H2-receptors as labeled with [125I]iodoaminopotentidine in the brains of patients affected by human neurodegenerative pathologies, as compared with control cases. The highest levels of histamine H2 binding sites in control cases were found in the caudate, putamen, and accumbens nuclei. In Huntington's chorea, the levels of histamine H2-receptor binding sites were found to be markedly decreased in virtually all regions examined, particularly in the putamen and globus pallidus lateralis. The loss of binding sites was related to the grade of the disease. Losses were more marked in grade III disease cases. The possible influence of neuroleptic treatment, commonly used in Huntington's patients, was studied by including samples from clinically treated schizophrenic patients. A moderate increase in the densities of [125I]iodoaminopotentidine was found in the globus pallidus of these patients. In Parkinson's disease, the levels of histamine H2-receptor binding sites were found not to be significantly different from those of control cases. These results were comparable with those obtained from unilaterally neurotoxin-lesioned guinea pigs. Similar losses of binding sites were observed in the quinolinic acid lesioned striatal intrinsic neurons in the guinea pig, whereas lesioning dopaminergic cell bodies in the substantia nigra with 6-hydroxydopamine did not produce any significant change. These results strongly suggest that histamine H2-receptors are expressed by striatal neurons, which degenerate in Huntington's chorea, but not by nigral dopaminergic neurons and may play a role in the regulation of the intact striato-nigral pathway.

Adult↗
PubMed1993

Alterations of the GluR-B AMPA receptor subunit flip/flop expression in kainate-induced epilepsy and ischemia.

In the hippocampus, glutamatergic pathways are altered following seizure activity or transient global ischemia, both pathological conditions leading to selective neuronal degeneration. Glutamatergic receptors, and notably alpha-amino-3-hydroxy-5-methyl-4-isoxazolopropionate (AMPA) receptors, a family of glutamate receptors involved in fast synaptic transmission and in the maintenance of synaptic potentiation may play an important role in the pathological outcome. AMPA receptors are assembled from GluR-A, GluR-B, GluR-C and GluR-D polypeptides which exist in flop and flip variants, the latter allowing larger glutamate responses. Using in situ hybridization techniques, we show that kainate-induced epilepsy provokes a rapid but transient increase (50%) of GluR-B flip mRNA levels in all subregions of the hippocampus (CA1, CA3, dentate gyrus). This early phase is followed by a second, persistent GluR-B flip increase in regions in which neurons are known to be seizure-resistant (i.e. CA1 an dentate gyrus) while a 35% decrease is observed in the vulnerable CA3 area. Following global ischemia, the levels of GluR-B flip and flop variants are dramatically reduced (90-100%), well before any morphological signs of cell death, in the subiculum and CA1, two areas known to be particularly sensitive to ischemic insult. In keeping with the properties of GluR flip variants, it is suggested that altered subunit stoichiometry may lead to long-lasting enhanced efficiency of fast synaptic transmission in the epileptic hippocampus. Since GluR-B containing receptors are Ca2+ impermeable, our results also suggest altered Ca2+ permeability in the vulnerable pyramidal neurons of areas CA3 and CA1 in the epileptic and ischemic hippocampi, respectively.

Animals↗
PubMed1993

A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas.

[3H](R)alpha-methylhistamine, a selective histamine H3-receptor ligand, was used to perform binding studies with membranes and generate light microscopic autoradiograms in sections of the rat brain. High densities of H3 receptors were found in membranes from the anterior part of the cerebral cortex, the accumbens nucleus, the striatum, the olfactory tubercles and the substantia nigra. Autoradiography of sagittal and frontal sections evidenced specific labelling in a number of gray matter areas over a very low background, as determined using thioperamide, a selective H3-receptor antagonist, as competing drug. Labelled areas were identified by comparison with adjacent Nissl-stained sections and their labelling was rated visually. H3 receptors are heterogeneously distributed among areas known to receive histaminergic projections. In the cerebral cortex, H3 receptors are present in all areas and layers, with a rostrocaudal gradient and a higher density in deep layers (laminae IV-VI). In the hippocampal formation, H3 receptors are the most abundant in the dentate gyrus and the subiculum. In the amygdaloid complex, the highest densities are found in the central, lateral and basolateral groups of nuclei. In the basal forebrain, the accumbens nucleus, the striatum, the olfactory tubercles and the globus pallidus are highly labelled. In the thalamus in which histaminergic fibres are scarce, H3 receptors are present in a rather high density, particularly in the midline, median and intralaminar groups of nuclei. In the hypothalamus, where the densest network of histaminergic fibres is found, H3 receptors occur in moderate density, being slightly more abundant in the anterior and medial part. They are also present at the level of the tuberomammillary nuclei where they may reside on histaminergic perikarya. In mesencephalon and lower brainstem, H3 receptors are abundant in the reticular part of the substantia nigra and central gray. They are present in low density in areas of noradrenergic and serotoninergic perikarya and in the spinal cord, where a faint specific labelling is detected in the gray matter, particularly in the external layers of the dorsal horn. In the cerebellum and pituitary gland, H3 receptors are scarce. Kainic acid infusions into the striatum were followed by marked local decreases in H3 receptors evidenced in both membrane binding and autoradiographic studies. Unilateral interruption of the ascending histaminergic pathways via electrocoagulation of the lateral hypothalamic area was followed by ipsilateral increase in striatal [3H](R)alpha-methylhistamine binding, a process consistent with denervation up regulation of postsynaptic H3 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Regional distribution of sulfonylurea receptors in the brain of rodent and primate.

Glibenclamide, one of the most potent antidiabetic sulfonylureas, inhibits the activity of ATP-sensitive K+ channels in the pancreas as well as in the brain through its binding to specific receptors. Quantitative autoradiography was used to localize such receptors in the brain of rat, mouse, guinea-pig and marmoset, using [3H]glibenclamide as radioligand. In all four species, specific glibenclamide binding sites were found to be heterogeneously distributed. The highest densities were in the cerebral cortex, the molecular layer of the cerebellar cortex, the thalamus and the caudate-putamen. The globus pallidus and the substantia nigra were highly labelled in rat and mouse but poorly labelled in guinea-pig and marmoset. The distribution of glibenclamide binding sites in the hippocampus was different between the rodents and marmoset; in rodents, most binding sites were distributed in the fascia dentata and the CA3-CA4 fields of Ammon's horn, contrasting with a very homogeneous distribution in all subfields of the marmoset hippocampus. In conclusion, we demonstrate that primate brain contains specific binding sites for [3H]glibenclamide with a distribution not exactly similar to that in rodent brain.

Animals↗
PubMed1993

Transient expression of the NR2C subunit of the NMDA receptor in developing rat brain.

Pharmacologically distinct NMDA-glutamate receptor subtypes have been reported in brain. We have studied the developmental expression of the mRNA encoding the NMDA receptor NR2C subunit in the rat brain by in situ hybridization. In contrast with the adult where no hybridization signal was detected in the hippocampus, a significant signal was seen in this formation during a restricted developmental period (P7-P14). The labelling covered large parts of the hippocampus including in particular the stratum radiatum, pyramidal and oriens layers of the CA1 area. The role of the NR2C subunit in neonatal NMDA receptor properties is discussed.

Animals↗
PubMed1993

Radioimmunocytochemical distribution of neutral endopeptidase (enkephalinase E.C.3.4.24.11) at the ultrastructural level in the rat median eminence.

Neutral endopeptidase (E.C.3.4.24.11) was visualized at the ultrastructural level in the external zone of the rat median eminence by using 125I-labelled IgG of a monoclonal serum. A precise analysis of the localization of the immunolabelling, which appears in the form of individual stray silver grains, was undertaken. Among the 1,045 grains counted, 82% were localized over membrane appositions involving nerve endings only and nerve endings plus tanycytes. The difference between the real and a randomly generated population of grains was statistically significant. Our results provide morphological arguments in support of the view of a paracrine action of neuropeptides present in the median eminence especially enkephalins but possibly, substance P, angiotensin, cholecystokinin and neurotensin. These neuropeptides are known to be inactivated by neutral endopeptidase. The action of these peptides may be exerted on nerve endings (autocrine or paracrine) but an intervention on tanycytes cannot be excluded.

Angiotensin II↗
PubMed1993

Regional variability in DNA fragmentation after global ischemia evidenced by combined histological and gel electrophoresis observations in the rat brain.

We have studied whether the delayed cell death induced by transient forebrain ischemia is associated with an internucleosomal cleavage of DNA into oligonucleosome-sized fragments. The integrity of genomic DNA in various brain regions after a 20-min four-vessel ischemia was examined using gel electrophoresis. We found typical ladders of oligonucleosomal DNA fragments in the striatum and in the Ammon's horn. In the latter we also often found a random DNA degradation as a smear pattern. These findings were reinforced by a specific in situ labeling of DNA breaks in tissue sections. A dark staining of nuclei was observed in the cell bodies of neurons--in particular in the head of the caudate and in the vulnerable CA1 hippocampal area. With biochemical and histological approaches, there was no evidence of DNA degradation in regions that are resistant to the injury. We conclude that the association of multiple mechanisms of cell damage may occur after a global ischemia. The regional variability in DNA fragmentation stresses the importance of using histological approaches in parallel with gel electrophoresis.

Animals↗