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Biomedical subjects

C Beaulieu

Publications and source records attributed to C Beaulieu.

At least 37 records · Page 2Linked to original sources

Benzophenones of Garcinia pseudoguttifera (Clusiaceae).

Four biogenetically related benzophenones have been isolated from the Fijian Garcinia pseudoguttifera. They are: 6-hydroxy-2,4-dimethoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (myrtiaphenone-A); 2,2-dimethyl-8-benzoyl-7-hydroxy-5-methoxy-6-(3-methyl-2-butenyl)benzopy ran (myrtiaphenone-B); 2,6-dihydroxy-4-methoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (vismiaphenone-C) and a new benzophenone, 2,2-dimethyl-8-benzoyl-3,7-dihydroxy-5-methoxy- 6-(3-methyl-2-butenyl)-3,4-dihydrobenzopyran (pseudoguttiaphenone-A). Pseudoguttiaphenone-A could be biogenetically derived from vismiaphenone-C. The major component of G. pseudoguttifera was identified as eupha-8,24-dien-3 beta-ol.

Benzophenones↗

Spatial encoding of hidden objects in dogs (Canis familiaris).

The authors investigated the type of spatial information that controls domestic dogs' (Canis familiaris) search behavior in a situation in which they have to locate a spatial position where they saw an object move and disappear. In Experiments 1 and 2, the authors manipulated all local and global sources of allocentric spatial information surrounding the hiding location. The results revealed that dogs relied on an egocentric frame of reference. Experiment 3 showed that dogs also encoded allocentric information when egocentric information was irrelevant. The authors conclude that dogs simultaneously encode both egocentric and allocentric spatial information to locate a spatial position, but they primarily base their search behavior on an egocentric frame of reference. The authors discuss under which natural conditions dogs might use these 2 sources of spatial information and detail the nature of spatial egocentric information and the circumstances underlying its use by dogs.

Animals↗

Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis.

BACKGROUND AND PURPOSE: The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome. METHODS: We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis. RESULTS: Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI. CONCLUSIONS: DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

Adult↗

Dynamics of cerebral injury, perfusion, and blood-brain barrier changes after temporary and permanent middle cerebral artery occlusion in the rat.

By means of magnetic resonance imaging (MRI) we longitudinally monitored the evolution of ischemic injury, changes in cerebral hemodynamics and alterations of the blood-brain barrier (BBB) during permanent or temporary middle cerebral artery occlusion (MCAO) in rats. Using the intraluminal suture occlusion model, male Sprague-Dawley rats were subjected to either permanent MCAO (Group A, n = 6), reperfusion after 1 h (Group B, n = 5), or reperfusion after 3 h (Group C, n = 5). Diffusion- and perfusion-weighted MRI and Gd-DTPA enhanced T1-weighted images were performed at six time points from 0.5 to 6 h post-MCAO. The lesion volume increased progressively in group A, decreased significantly in group B (P<0.01), and only showed a tendency toward reduction in group C. Perfusion-weighted MRI delineated severe perfusion deficits in the ischemic core, confirmed early and late reperfusion, and was able to demonstrate postischemic hyperperfusion in group C. Gd-DTPA extravasation was found in all animals with permanent MCAO and initially became grossly visible between 4.5 and 6 h post-MCAO. While only 2 animals demonstrated contrast enhancement in group B, widespread BBB changes were detected immediately following late reperfusion (Group C). Our results demonstrate that with advanced MRI techniques, alterations of the BBB can be correlated with the hemodynamic and biophysical consequences of reperfusion.

Animals↗

Evaluation of early reperfusion and i.v. tPA therapy using diffusion- and perfusion-weighted MRI.

OBJECTIVE: To characterize the effects of recombinant tissue plasminogen activator (rt-PA) therapy and early reperfusion on diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) changes observed following acute ischemic injury. METHODS: Twelve patients were evaluated prospectively using echo planar DWI and bolus tracking PWI. Six patients received i.v. rt-PA 0.9 mg/kg and were compared with six patients who did not. Patients receiving rt-PA were initially imaged (T1) 3 to 5 hours postictus (mean, 4 hours 20 minutes) whereas those not treated with tissue plasminogen activator (tPA) were imaged 4 to 7 hours postictus (mean, 5 hours, 25 minutes). Follow-up imaging was performed 3 to 6 hours (T2), 24 to 36 hours (T3), 5 to 7 days (T4), and 30 days (T5) after the first scan in all patients. Lesion volumes were measured on both DWI and time-to-peak maps constructed from PW images. RESULTS: PWI was performed successfully at T1 and T3 in 11 of 12 patients. In the group that received i.v. tPA, initial PWI volumes were less than DWI volumes in five of six patients (83%), whereas only one of five patients (20%) not receiving tPA had PWI < DWI volume (p = 0.08). PWI normalized by 24 to 36 hours (T3) in 6 of 11 patients (early reperfusers), with 5 of 6 of these early reperfusers having received tPA. The aggregate apparent diffusion coefficient (ADC) values for the early reperfusers were consistently higher at T2 (p = 0.04), T3 (p = 0.002), and T4 (p = 0.0005). Five of six patients with early reperfusion demonstrated regions of elevated ADC within the ischemic zone (mean ipsilateral ADC/contralateral ADC, 1.46 +/- 0.19) by 24 to 36 hours, whereas none of the nonearly reperfusers showed these regions of elevated ADC (p = 0.015). CONCLUSION: Early reperfusion is seen more frequently with i.v. tPA therapy. In addition, the study showed that ADC may undergo early increases that are tied closely to reperfusion, and marked ADC heterogeneity may exist within the same lesion. Early reperfusion is seen more frequently with i.v. tPA therapy.

Aged↗

Tau-mediated process outgrowth is differentially altered by the expression of MAP2b and MAP2c in Sf9 cells.

It is well documented that the MAPs, MAP2 and tau, play pivotal roles in neurite outgrowth. Several isoforms of MAP2 and tau are coexpressed in neurons, suggesting that the pattern of neurite outgrowth results from a functional equilibrium among these isoforms. In the present study, by coexpressing two of these MAPs at the same time in Sf9 cells, we demonstrated that tau-mediated process outgrowth is affected differently by MAP2b and MAP2c. MAP2b impairs tau ability to induce process outgrowth. Tau affects MAP2c capacity to induce the formation of multiple processes. There is evidence that actin microfilaments (F-actin) are involved in the elaboration of tau-mediated process outgrowth in Sf9 cells. We compared the effects of MAP2b and MAP2c with the effects of tau on F-actin distribution and stability in Sf9 cells. In MAP2b- and MAP2c-expressing cells with processes, F-actin was redistributed. However, in MAP2b-expressing cells without processes, the distribution of F-actin appears to be similar to the one in wild-type infected cells. Collectively, these results indicate that MAP2b could impair the ability of MAP2c and tau to redistribute F-actin in Sf9 cells, thereby decreasing their capacity to induce process formation. Furthermore, MAP2b and MAP2c patterns of process outgrowth were differentially modified by depolymerization of F-actin by cytochalasin D (CD). As previously reported for tau-expressing cells, the MAP2b-expressing cells developed a higher number of processes per cell and a higher number of cells presented processes in the presence of CD. However, the number of cells with multiple processes was lower in MAP2b-expressing cells than in tau-expressing cells treated with CD at 24 h postinfection. This suggests that MAP2b exerts an effect on F-actin stability at an earlier stage of infection than tau. MAP2c had also some stabilizing effects on F-actin at an early stage of infection, since the percentage of cells presenting one process was similar to the nontreated cells. Therefore, MAP2b seems to have less capacity than MAP2c to redistribute F-actin but, nonetheless, both of these MAP2 isoforms exert a stabilizing effect on F-actin at an early stage of infection. Finally, by modifying phosphorylation we showed that MAP2c capacity to induce multiple processes is related to protein phosphorylation in Sf9 cells. Therefore, the differential effect of MAP2c and MAP2b on process outgrowth seems also to depend on protein phosphorylation.

Actins↗

Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: evolution of lesion volume and correlation with clinical outcome.

A prospective longitudinal diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia-induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.

Aged↗

Alterations of perisomatic GABA synapses on hippocampal CA1 inhibitory interneurons and pyramidal cells in the kainate model of epilepsy.

In the kainate model of epilepsy, electrophysiological and anatomical modifications occur in inhibitory circuits of the CA1 region of the rat hippocampus. Using postembedding GABA immunocytochemistry and electron microscopy, we characterized perisomatic GABA and non-GABA synaptic contacts in CA pyramidal cells, and GABAergic interneurons of stratum oriens/alveus and stratum lacunosum-moleculare, and examined if changes occurred at these synapses at two weeks post-kainate treatment. We found that, in control rats, the number and total length of perisomatic GABA synapses were significantly smaller (approximately 40-50%) in lacunosum-moleculare interneurons than in oriens/alveus interneurons and pyramidal cells. Additionally, the number and total length of perisomatic non-GABA synapses were different among all cell types, with these parameters increasing significantly in the following order: pyramidal cells<lacunosum-moleculare interneurons<oriens/alveus interneurons. Following kainate treatment, we found that the number and total length of GABA synapses were significantly increased in lacunosum-moleculare interneurons (by 76% and 100%, respectively), but were unchanged in pyramidal cells and oriens/alveus interneurons. In addition, the mean length of individual GABA synapses was significantly increased (by 17%) in pyramidal cells after kainate treatment. In contrast, no changes were observed at non-GABA synapses in any cell type examined after kainate treatment. These results indicate that, in control animals, the ultrastructural correlates of perisomatic GABA inhibition are less pronounced in lacunosum-moleculare than oriens/alveus interneurons or pyramidal cells, whereas those of perisomatic excitation are more prominent in oriens/alveus than lacunosum-moleculare interneurons, and much less present in pyramidal cells. In addition, our results with kainate-treated animals suggest that cell-specific changes in perisomatic inhibition may occur in CA1 inhibitory interneurons in the chronically hyperexcitable hippocampus. The ultrastructural correlates of perisomatic inhibition were increased in lacunosum-moleculare interneurons, which may thus suggest some disinhibition of pyramidal cells. However, the ultrastructural correlates of perisomatic inhibition were increased in pyramidal cells, implying some enhancement of perisomatic inhibition of principal cells in the hyperexcitable hippocampus.

Animals↗

Diffusion-weighted magnetic resonance imaging: theory and potential applications to child neurology.

Magnetic resonance imaging (MRI) is an excellent tool for the investigation of neurological disorders in children. Diffusion-weighted MRI (DWI) is sensitive to the diffusion (or molecular displacement) of water in tissue. The purpose of this article is to describe briefly the basic theory behind DWI and to discuss its potential applications to neurological disorders in children. We demonstrate that DWI is a sensitive technique for the detection of acute brain injury, and that it is well suited for monitoring brain development, particularly myelination and white matter changes.

Acute Disease↗

Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia. Effects of hypoglycemia, hyperglycemia, and TTX.

BACKGROUND AND PURPOSE: The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia. METHODS: Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application. Cardiac arrest was effected by intravenous KCl injection during serial high-speed diffusion and blood oxygenation-sensitive gradient-recalled echo MRI. Brain DC potential was recorded simultaneously. Serial ADC maps were calculated from the diffusion-weighted data and fitted to a model function to measure the delay between cardiac arrest and rapid ADC decrease. RESULTS: The time of anoxic depolarization indicated by DC change agreed well with the rapid drop in ADC in all groups; both were accelerated with hypoglycemia and delayed by hyperglycemia. A more gradual ADC decline occurred before anoxic depolarization, which was more pronounced in hyperglycemic animals and less pronounced in hypoglycemic animals. Rapid drop in ADC was also delayed by local TTX application. Changes in gradient-recalled echo image intensity were not significantly different among groups. CONCLUSIONS: While much of the ADC decrease in ischemia occurs during anoxic depolarization, significant but gradual ADC changes occur earlier that may not be due to a massive loss in ion homeostasis.

Animals↗

Decompressive craniectomy, reperfusion, or a combination for early treatment of acute "malignant" cerebral hemispheric stroke in rats? Potential mechanisms studied by MRI.

BACKGROUND AND PURPOSE: Both early reperfusion and decompressive craniectomy have proved beneficial in the treatment of large space-occupying "malignant" hemispheric stroke. The aim of this study was to directly compare the benefit of reperfusion with that of craniectomy and to study the effects of combined treatment in a rat model of focal cerebral ischemia. METHODS: Cerebral ischemia was introduced in 28 rats. Four groups were investigated: (1) no treatment, (2) decompressive craniectomy, (3) reperfusion, and (4) reperfusion and craniectomy as treatment at 1 hour after middle cerebral artery occlusion. Perfusion- and diffusion-weighted MRI were performed serially from 0.5 to 6 hours after middle cerebral artery occlusion. RESULTS: The 6-hour DWI-derived hemispheric lesion volumes in the reperfusion group (10.2+/-3.9%), the craniectomy group (23.0+/-6.4%), and the combination group (21.8+/-12.4) were significantly smaller than that in the control group (44.1+/-5.4%) (P<0.05). Reperfusion, craniectomy, and combined treatment led to higher perfusion in the cortex compared with the control group, whereas only reperfused animals achieved significantly higher perfusion in the basal ganglia. In 5 animals, combined reperfusion and decompressive craniectomy resulted in an early contrast media enhancement. CONCLUSIONS: Early reperfusion and craniectomy were shown to be effective in decreasing infarction volume by improving cerebral perfusion. Reperfusion remains the best therapy in malignant hemispheric stroke. Combined treatment yields no additional benefit compared with single treatment, probably because of early blood-brain barrier breakdown.

Acute Disease↗

Increased number and size of dendritic spines in ipsilateral barrel field cortex following unilateral whisker trimming in postnatal rat.

The barrel field area of the primary somatosensory cortex of rodents is a fertile ground for investigating experience-dependent plasticity and its mechanisms, because the neurons in its layer IV are distributed in groups (barrels) which correspond somatotopically to the vibrissae of the contralateral facial pad. After removal of three rows of whiskers from the right facial pad of young rats during the first two postnatal months, we looked for eventual changes in dendritic spine number and morphology in the corresponding barrels ipsi- and contralateral to the deprivation. Intact littermate controls were also examined. Spine number was determined by means of the unbiased disector method in electron micrographs from serial thin sections processed for post-embedding gamma-aminobutyric acid (GABA) immunocytochemistry. The volume and surface area of spine head, surface area of postsynaptic density and length of spine neck were measured from computerized three-dimensional reconstructions. Even though there was no significant side-to-side difference in the numerical density of dendritic spines in the experimental animals, the total number of spines in the ipsilateral barrels had increased by 67%, in view of the greater thickness of layer IV on this side. Moreover, spine head volume and surface area of postsynaptic densities were increased, and the length of spine neck was reduced in the ipsilateral compared to the contralateral cortex, and similar differences were noticeable between ipsilateral and control cortex. These changes apparently involved not only the predominant population of relatively small, dendritic spines innervated by asymmetrical synaptic terminals, but also the relatively small contingent of larger spines receiving symmetrical synapses formed by GABA terminals. The most likely explanation for such ipsilateral changes was an increased use of the intact (contralateral) facial pad during postnatal life, in keeping with the notion that activation of a peripheral sensory apparatus during the early postnatal period may have profound effects on the neuronal morphology and structural design of the primary somatosensory cortex. A possible mechanism in this case might be the excessive early activation of thalamic afferents, resulting in increased production of trophic factors, such as brain-derived nerve growth factor.

Animals↗

Developmental changes in expression of myotonic dystrophy protein kinase in the rat central nervous system.

Myotonic dystrophy protein kinase (DMPK) is the protein product of the genetic locus associated with myotonic dystrophy, in which alterations of muscle excitability, cardiac conduction defects, mental retardation, and cognitive deficiencies are inherited as an autosomal dominant trait. DMPK belongs to a novel protein serine/threonine kinase family, but its regulation and physiological functions have not been specified. In a first step toward understanding the functions of DMPK in the central nervous system, we have characterized its localization and developmental pattern of expression in rat brain and spinal cord by using a monospecific rabbit antiserum produced against bacterially expressed DMPK. Expression of DMPK begins after birth and increases gradually to peak at postnatal day 21 with antibody labeling of neuronal cell types in many regions. After postnatal day 21 and proceeding to the adult, the pattern of expression becomes more restricted, with localization to certain regions or cell groups in the central nervous system. Electron microscopy reveals localization within adult spinal motor neurons to the endoplasmic reticulum and dendritic microtubules. The adult localizations suggest that DMPK may function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control.

Animals↗

Quantified distribution of serotonin transporter and receptors during the postnatal development of the rat barrel field cortex.

Serotonin membrane transporter and 5-HT1B and 5-HT2A receptors were visualized and measured by autoradiography in the rat barrel field cortex at postnatal days 4, 8, 12, 16 and in adult (> P60). [3H]citalopram binding, reflecting the presence of 5-HT transporter on thalamocortical fibers, produced a clearcut barrel pattern from P4 to P16 (peak at P8), and decreased to a dispersed, low density in the adult. The patterning and temporal profile of 5-HT1B receptor binding ([125I]cyanopindolol) followed a parallel course. The 5-HT2A receptor binding ([125I]DOI) also conformed transiently to a barrel pattern; it increased in density from P8 to P16 and returned to a level as low as at P4 in the adult. These data suggest that 5-HT exerts a dual role in the developing somatosensory cortex: a local regulation of the peripherally-induced activity of thalamocortical axons via 5-HT1B receptors, and a trophic-like influence mediated by 5-HT2A receptors and possibly involving BDNF.

Aging↗

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve.

We report here a study of longitudinal relaxation (T1) and magnetisation transfer (MT) in peripheral nerve. Amphibian sciatic nerve was maintained in vitro and studied at a magnetic field strength of 3 T. A CPMG pulse sequence was modified to include either a saturation pulse to measure T1 relaxation or an off-resonance RF irradiation pulse to measure MT. The resulting transverse relaxation (T2) spectra yielded four components corresponding to three nerve compartments, taken to result from myelinic, axonal, and inter-axonal water, and a fourth corresponding to the buffer solution water in which the nerve sample was bathed. Each nerve component was analysed for T1 relaxation and MT. All three nerve T2 components exhibited unique T1 relaxation and MT characteristics, providing further support for the assignment of the components to unique physical compartments of water. Numerical investigation of T1sat measurements of each of the three nerve T2 components indicates that while the two shorter-lived exhibit similar steady-state magnetisation transfer ratios (MTRs), their respective MT properties are quite different. Simulations demonstrate that mobile water exchange between these two components is not necessary to explain their similar steady-state MTR. In the context of the assignment of these two components to signal from myelinic and axonal water, this is to say that these two microanatomical regions of nerve may exhibit similar steady-state MTR characteristics despite possessing widely different MT exchange rates. Therefore, interpreting changes in MTR solely to reflect a change in degree of myelination could lead to erroneous conclusions.

Animals↗

Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve.

The influence of compartmental boundaries on water proton transverse relaxation and diffusion measurements was investigated in three distinct excised nerves, namely, the non-myelinated olfactory nerve, the Schwann cell myelinated trigeminal nerve, and the oligodendrocyte myelinated optic nerve of the garfish. The transverse relaxation decay curves were multiexponential and their decomposition yielded three primary components with T2 values approximately 30-50, 150, and 500 ms, which were subsequently assigned to water protons in the myelin, axoplasm, and interaxonal compartments. The short T2 component was absent in the non-myelinated olfactory nerve, but present in both myelinated nerves and thus provides supporting evidence for the use of quantitative T2 measurements to measure the degree of myelination. The signal contribution of each T2 component to the apparent diffusion coefficient measurements was varied by incrementing the spin-echo time with a preparatory CPMG train of radiofrequency pulses. The apparent diffusion coefficient and its anisotropy were shown to be independent of the spin-echo time over the range of 70 to 450 ms.

Algorithms↗

Selective loss of GABA neurons in area CA1 of the rat hippocampus after intraventricular kainate.

The intraventricular injection of kainic acid (KA) in rats produces a loss of dentate hilar neurons and hippocampal CA3 pyramidal cells, and renders the dentate granule cells and the CA1 pyramidal cells hyperexcitable. We have used immunocytochemical detection of glutamic acid decarboxylase (GAD), a marker of gamma-aminobutyric acid (GABA) cells, as well as stereological cell counting techniques, to determine whether inhibitory cell loss was present 2 weeks after KA treatment. In area CA1, we found that the density of GAD-positive cells was reduced by KA, but only in stratum oriens and the alveus. Counts of Nissl-stained neurons were also significantly reduced in this layer. These results demonstrate a loss of GABA cells in the basal dendritic layer of the CA1 region, which may underlie the hyperexcitability of CA1 pyramidal cells following KA treatment.

Animals↗