Search PubMed⌕ Search

Biomedical subjects

H Benveniste

Publications and source records attributed to H Benveniste.

15 recordsLinked to original sources
PubMed1992

Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy.

BACKGROUND AND PURPOSE: The aim of this study was to measure apparent diffusion coefficients in rat brain tissue exposed to ouabain, glutamate, and N-methyl-D-aspartate and to compare them with apparent diffusion coefficients found in acute cerebral ischemia. METHODS: The apparent diffusion coefficient was measured using magnetic resonance microscopy in four groups of Sprague-Dawley rats after occlusion of the right middle cerebral artery and ipsilateral common carotid artery (n = 7), after ouabain exposure (n = 6), during glutamate exposure (n = 7), or during N-methyl-D-aspartate exposure (n = 3). Ouabain, glutamate, and N-methyl-D-aspartate were applied via an intracerebrally implanted microdialysis membrane. RESULTS: Three hours after the induction of focal cerebral ischemia, a 33% reduction in the apparent diffusion coefficient was observed in the right dorsolateral corpus striatum and olfactory cortex. After ouabain exposure, reductions in the apparent diffusion coefficient were observed within a 1,500-microns radius of the microdialysis membrane. Quantitative analysis revealed that apparent diffusion coefficient values in ischemic and ouabain-exposed tissue fell within the same range. Glutamate and N-methyl-D-aspartate reduced the brain tissue apparent diffusion coefficient by 35% and 40%, respectively. CONCLUSIONS: On the basis of these findings, we conclude that ischemia-induced apparent diffusion coefficient reductions are likely caused by a shift of extracellular to intracellular water.

Acute Disease↗
PubMed1991

Diffusion/microcirculation MRI in the rat brain.

The CO2 fraction of an anesthetized rat's breathing mixture was changed (from 0 to 10%) to attempt to change the brain microcirculation and observe these changes in diffusion measurements of the neural tissue. Brain apparent diffusion coefficients were measured to be (0.71 +/- 0.01) X 10(-3) mm2/s before sacrifice and (0.39 +/- 0.01) X 10(-3) mm2/s after sacrifice. Multiple diffusion components were observed, consistent with flowing material, but the extra components did not increase with increased CO2. It is proposed that the additional components may be due to extracellular, extravascular water such as CSF.

Animals↗
PubMed1991

Decreased glucose utilization in discrete brain regions of rat in thioacetamide-induced hepatic encephalopathy as measured with [3H]-deoxyglucose.

To evaluate the possible contribution of bioenergetic failure in the particular brain regions to the pathomechanism of hepatic encephalopathy (HE), local cerebral metabolic rate for glucose (LCMRglue) was evaluated from [3H]-deoxyglucose uptake in frontal, visual and auditory cortex, striatum, cerebellum and medulla oblongata of rats with acute HE induced with a hepatotoxin--thioacetamide (TAA). HE caused a decrease of LCMRglue in all the regions studied. The strongest decrease (about 65%) was noted in hippocampus and cerebral cortex--the two regions rich in glutamatergic neurons. The results indicate a possible link between decreased energy metabolism and impaired excitatory, glutamatergic neurotransmission--the two factors whose contribution to HE has so far been implicated separately.

Animals↗
PubMed1991

Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain.

Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging.

Animals↗
PubMed1991

The excitotoxin hypothesis in relation to cerebral ischemia.

The distribution of brain cell injury following transient ischemia is remarkable because only certain neurons in distinct brain regions are destroyed (selective neuronal death). Because excitatory neurotransmitters (glutamate and aspartate) cause a similar pattern of selective neuronal death, it seemed only natural to associate these effects with the trauma of ischemia. This led to the formulation of the excitotoxin hypothesis, which explains selective neuronal death as a result of excessive interstitial concentration increases of excitatory amino acids during ischemia, resulting in the opening of receptor-coupled ionophores, of which calcium channels are of particular interest. A large influx of calcium associated with impaired intracellular calcium sequestration mechanisms due to energy failure activates a host of catabolic enzymes that ultimately will cause neuronal death. The purpose of this work was (a) to measure extracellular glutamate concentration increases during ischemia in a selective vulnerable brain region (rat CA1 hippocampus), (b) to evaluate the toxicity of such a concentration increase, and (c) to investigate the relationship between ischemia-induced glutamate accumulation and changes of calcium homeostasis. The execution of these experiments required a method that was able to sample excitatory amino acids in the brain extracellular space for subsequent analysis by high performance liquid chromatography (HPLC). The choice of the microdialysis technique proved most satisfactory and further mathematical analysis made it possible to transform dialysate glutamate concentrations to extracellular concentrations. The study demonstrated that extracellular glutamate in CA1 reached toxic concentrations during ischemia. There appeared to be a clear correlation between ischemia-induced glutamate accumulation and the decrease in extracellular calcium since both changes were prevented in the denervated CA1 (the destruction of glutamatergic innervation from CA3 protects CA1 pyramidal neurons from ischemic damage). By contrast, blockade of N-methyl-D-aspartate (NMDA) receptors with the glutamate antagonist APV was only partially effective in preventing the ischemia-induced calcium changes in CA1. Taken together, these results support the excitotoxin hypothesis but question the rational of treating neuronal injury caused by transient global ischemia exclusively with NMDA antagonists.

Amino Acids↗
PubMed1989

Ischemic damage in hippocampal CA1 is dependent on glutamate release and intact innervation from CA3.

The removal of glutamatergic afferents to CA1 by destruction of the CA3 region is known to protect CA1 pyramidal cells against 10 min of transient global ischemia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CA1 hippocampal tissue. In intact CA1 hippocampal tissue, glutamate increased sixfold during ischemia; in the CA3-lesioned CA1 region, however, glutamate only increased 1.4-fold during ischemia. To assess the neurotoxic potential of the ischemia-induced release of glutamate, we injected the same concentration of glutamate into the CA1 region as is released during ischemia in normal, CA3-lesioned, and ischemic CA1 tissue. We found that this particular concentration of glutamate was sufficient to destroy CA1 pyramids in the vicinity of the injection site in intact and CA3-lesioned CA1 tissue when administered during control (non-ischemic) conditions. In contrast, the same amount injected during ischemia in the CA3-lesioned CA1 region destroyed pyramidal cells in a widely distributed zone around the injection site in the CA1 region. It is concluded that the ischemia-induced damage of pyramidal cells in CA1 is dependent on glutamate release and intact innervation from CA3.

Amino Acids↗
PubMed1989

Determination of brain interstitial concentrations by microdialysis.

Microdialysis is an extensively used technique for the study of solutes in brain interstitial space. The method is based on collection of substances by diffusion across a dialysis membrane positioned in the brain. The outflow concentration reflects the interstitial concentration of the substance of interest, but the relationship between these two entities is at present unclear. So far, most evaluations have been based solely on calibrations in saline. This procedure is misleading, because the ease by which molecules in saline diffuse into the probe is different from that of tissue. We describe here a mathematical analysis of mass transport into the dialysis probe in tissue based on diffusion equations in complex media. The main finding is that diffusion characteristics of a given substance have to be included in the formula. These include the tortuosity factor (lambda) and the extracellular volume fraction (alpha). We have substantiated this by studies in a well-defined complex medium (red blood cell suspensions) as well as in brain. We conclude that the traditional calculation procedure results in interstitial concentrations that are too low by a factor of lambda 2/alpha for a given compound.

Animals↗
PubMed1988

Early postischemic 45Ca accumulation in rat dentate hilus.

Several studies have found postischemic regional accumulation of calcium to be time-dependent and coincident with the progression of ischemic cell change. In the most vulnerable cells in the hippocampus one would therefore expect to find a primary and specific early uptake of calcium after ischemia. Autoradiograms of 45Ca and 3H-inulin distribution were investigated before and 1 h after 20 min ischemia in the rat hippocampus. Two different methodological approaches were used for administration of 45Ca: (a) administration via microdialysis probes, (b) intraventricular injection. During control conditions the 45Ca autoradiograms showed variations in distribution volume in accordance with 3H-inulin determination of extracellular space size. One hour after ischemia a massive accumulation of 45Ca was found in the dentate hilus. No change in the distribution pattern of 3H-inulin could be demonstrated 1 h after ischemia. We suggest that 45Ca accumulation in dentate hilus 1 h after ischemia is a result of increased Ca2+ uptake before irreversible cell damage occurs and is not due to passive influx of calcium across a leaky plasma membrane.

Animals↗
PubMed1988

Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia.

Rats exposed to 10 min of complete cerebral ischemia develop necrosis of the CA-1 region of the hippocampus after 2-3 days. We studied the involvement of synaptic transmission for this process by ablation of the afferent input (which is mainly glutamatergic) to CA1 by bilateral destruction of CA-3 neurons (Schafferotomi). The deafferentiation completely prevented the ischemic nerve cell destruction as revealed by histological studies after 6 days. The role of intracellular Ca++ overload was assessed by measurement of the interstitial Ca++ concentration. In control animals the interstitial Ca++ concentration decreases abruptly to 10% of the initial value 1.6 min after the onset of ischemia. The denervated hippocampi, however, showed no decrease during the 10 min of ischemia and hippocampi injected with 2-amino-5-phosphovalerate (APV), a competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptors, displayed a significantly reduced decrease (45% of the initial value) during ischemia. It is concluded that calcium influx via the glutamate-operated channels during the ischemic period is an important link in the development of ischemic brain cell damage.

2-Amino-5-phosphonovalerate↗
PubMed1985

Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro.

The uptake and release of D-[3H]aspartate (used as a tracer for endogenous glutamate and aspartate) were studied in cultured glutamatergic neurons (cerebellar granule cells) and astrocytes at normal (5 mM) or high (55 mM) potassium and under conditions of hypoglycemia, anoxia or "ischemia" (combined hypoglycemia and anoxia). In glutamatergic neurons it was found that "ischemic" conditions led to a 2.4-fold increase in the potassium-induced release of D-[3H]aspartate as compared to normal conditions. Hypoglycemia or anoxia alone affected the release only marginally. The ischemia-induced induced increase in the evoked D-[3H]aspartate release was shown to be calcium-dependent. In astrocytes no difference was found in the potassium-induced release between the four conditions and the K+-induced release was not calcium-dependent. The uptake of D-[3H]aspartate was found to be stimulated at high potassium in both glutamatergic neurons (98%) and in astrocytes (70%). This stimulation of D-aspartate uptake, however, was significantly reduced under conditions of anoxia or "ischemia" in both cell types. In glutamatergic neurons (but not in astrocytes) hypoglycemia also decreased the potassium stimulation of D-aspartate uptake. In a previous report it was shown, using the microdialysis technique, that during transient cerebral ischemia in vivo the extracellular glutamate content in hippocampus was increased eightfold. In the present paper it is shown that essentially no increase in extracellular glutamate is seen under ischemia when the perfusion is performed using calcium-free, cobalt-containing perfusion media. The results from the in vitro and in vivo experiments indicate that the glutamate accumulated extracellularly under ischemia in vivo originates from transmitter pools in glutamatergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Maximization of contrast-to-noise ratio to distinguish diffusion and microcirculatory flow.

Optimization of the contrast-to-noise ratio (CNR) is described for microcirculation magnetic resonance (MR) imaging techniques based on flow-compensated/flow-dephased sequences, both with and without even-echo rephasing. The authors present the most advantageous manner of applying flow-dephased gradients, such that dephasing is maximal while diffusion losses are minimal. The theoretical considerations include phase, diffusion, echo time, and bandwidth in the determination of the optimal parameters for microcirculation imaging. Studies in phantoms consisting of stationary and flowing copper sulfate in Sephadex columns demonstrate the validity of the calculations. Optimized in vivo images of a rat stroke model demonstrate the potential of the flow-compensated/flow-dephased technique and the importance of optimizing CNR.

Animals↗
PubMedDate not supplied

MR imaging of microcirculation in rat brain: correlation with carbon dioxide-induced changes in blood flow.

Considerable interest has been shown in developing a magnetic resonance (MR) imaging technique with quantitative capability in the evaluation of tissue microcirculation ("perfusion"). In the present study, the flow-dephased/flow-compensated (FD/FC) technique is evaluated for measuring rat cerebral blood flow (CBF) under nearly optimal laboratory conditions. Imaging was performed on a 2.0-T system equipped with shielded gradient coils. Rat CBF was varied by manipulating arterial carbon dioxide pressure (PaCO2). In parallel experiments, optimized MR imaging studies (seven rats) were compared with laser Doppler flowmetry (LDF) studies (nine rats). LDF values showed a high degree of correlation between CBF and PaCO2, agreeing with results in the literature. MR imaging values, while correlating with PaCO2, showed considerable scatter. The most likely explanation is unavoidable rat motion during the requisite long imaging times. Because of this motion sensitivity, the FD/FC technique cannot provide a quantitative measure of CBF. It can, however, provide a qualitative picture.

Animals↗
PubMedDate not supplied

Direct digitization of optical images using a photostimulable phosphor system.

The authors describe a method for directly digitizing optical images with a photostimulable phosphor (PSP) system. A PSP plate is initially charged with an exposure to a uniform x-ray field, and is then exposed to an optical image which discharges the plate in relation to the amount of incident light. Two applications were investigated: a contact-print technique for digitizing film radiographs, and a projection technique for digitizing transparent objects such as histology slides. Spatial uniformity was found to be adequate, and linearity of optical density response was excellent from 0.0-2.9 o.d. after look-up table correction. Spatial frequency response was degraded with the optical technique relative to the x-ray imaging properties of the plates, but was restorable by Fourier filtering. Image noise following spatial enhancement was satisfactory at intermediate to high optical densities using a high-resolution PSP plate, but was somewhat degraded at low densities.

Humans↗