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J Peeling

Publications and source records attributed to J Peeling.

At least 37 records · Page 2Linked to original sources
PubMed1998

Temporal profile of magnetic resonance imaging changes following forebrain ischemia in the gerbil.

Quantitative T2 magnetic resonance (MR) imaging was used to examine gerbil brains 1, 3, 10, and 30 days after 5 min forebrain ischemia. T2 was increased in the dorsal-lateral striatum 1 and 3 days post-ischemia, and in the hippocampus 3 days post-ischemia. T2 was normal 10 days post-ischemia, and decreased in the hippocampus and dorsal-lateral striatum 30 days post-ischemia. Neuronal counts in the dorsal-lateral striatum and CA1 hippocampal region were uniformly decreased 30 days post-ischemia. The increase in T2 shortly after ischemia is attributed to brain edema localized to regions where neuronal injury developed. The late decrease in T2 may be due to decreased water in gliotic tissue, or to ferritin-positive microglia, following forebrain ischemia. Tissue atrophy at later times gave enlarged ventricles on MR images.

Animals↗
PubMed1998

Protective effects of free radical inhibitors in intracerebral hemorrhage in rat.

Iron compounds formed in the degradation of a hematoma can accelerate the formation of free radicals in adjacent ischemic or hypoperfused tissue. The purpose of this study was to examine the efficacy of compounds that quench free radicals in improving the outcome in rats with experimental intracerebral hemorrhage. Intracerebral hemorrhage was induced in rats by injection of bacterial collagenase and heparin into the caudate nucleus. Rats were treated with alpha-tocopherol plus ascorbic acid starting before hemorrhage, or with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone starting 2 h after hemorrhage, with treatment continued for 10 days after induction of hemorrhage. Outcome was assessed by behavioral analyses, magnetic resonance imaging, and histopathology. A trend towards behavioral improvement was found for rats treated with alpha-tocopherol/ascorbic acid, while behavior was significantly improved following intracerebral hemorrhage in rats treated with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone. These results suggest that free radicals may play a role in the development of brain injury following intracerebral hemorrhage, and that compounds that interrupt the free radical cascade may improve outcome. However, treatment did not significantly affect edema, resolution of the hematoma, or neuronal injury in tissue adjacent to the hemorrhage.

Animals↗
PubMed1998

Intraventricular injection of human immunodeficiency virus type 1 (HIV-1) tat protein causes inflammation, gliosis, apoptosis, and ventricular enlargement.

To determine the role of the Tat protein of the human immunodeficiency virus type 1 (HIV-1) in the pathogenesis of HIV-1 associated dementia, recombinant Tat was injected intraventricularly as a single or repeated dose into male Sprague-Dawley rats. Histopathological evaluation showed an initial infiltration of neutrophils one day after Tat injection, followed by macrophages and lymphocytes by 7 days. Tat-injected brains also exhibited astrocytosis, apoptotic cells, and ventricular enlargement 7 days following the last injection. Nuclear magnetic resonance spectroscopic analysis of tissue extracts of hippocampi from Tat-injected rats showed a decrease in the glutamate/g aminobutyric acid ratio. We conclude that the transient extracellular exposure of the central nervous system to Tat protein of HIV can cause a cascade of events leading to the influx of inflammatory cells, glial cell activation, and neurotoxicity.

Animals↗
PubMed1998

Neurovirulence in feline immunodeficiency virus-infected neonatal cats is viral strain specific and dependent on systemic immune suppression.

Feline immunodeficiency virus (FIV) is a lentivirus that causes immune suppression and neurological disease in cats. Among animal viruses, individual viral strains have been shown to be neurovirulent, but the role of viral strain specificity among lentiviruses and its relationship to systemic immune suppression in the development of neurological disease remains uncertain. To determine the extent to which different FIV strains caused neurological disease, FIV V1CSF and Petaluma were compared in ex vivo assays and in vivo. Both viruses infected and replicated in macrophage and mixed glial cell cultures at similar levels, but V1CSF induced significantly greater neuronal death than Petaluma in a neurotoxicity assay. V1CSF-infected animals showed significant neurodevelopmental delay compared to the Petaluma-infected and uninfected animals. Magnetic resonance spectroscopy studies of frontal cortex revealed significantly reduced N-acetyl aspartate/creatine ratios in the V1CSF group compared to the other groups. Cyclosporin A treatment of Petaluma-infected animals caused neurodevelopmental delay and reduced N-acetyl aspartate/creatine ratios in the brain. Reduced CD4(+) and CD8(+) cell counts were observed in the V1CSF-infected group compared to the uninfected and Petaluma-infected groups. These findings suggest that neurodevelopmental delay and neuronal injury is FIV strain specific but that systemic immune suppression is also an important determinant of FIV-induced neurovirulence.

Animals↗
PubMed1998

A review of in vivo 1H magnetic resonance spectroscopy of cerebral ischemia in rats.

A number of metabolic alterations are initiated by cerebral ischemia including dramatic increases in lactate concentration, decreases in N-acetylaspartate, choline, and creatine concentrations, as well as changes in amino acid levels. A review of proton nuclear magnetic resonance spectroscopy studies of focal and global cerebral ischemia in rats is presented here. In particular, studies in neonatal rats have shown that a continued elevation of lactate levels without recovery after hypoxia-ischemia or a decrease in N-acetylaspartate concentration at any time are indicative of deleterious outcome. Studies of the effect of temperature on ischemic damage in a model of focal ischemia showed that outcome improved with mild hypothermia. Again, lack of recovery of lactate upon reperfusion was shown to be indicative of poor outcome. Dichloroacetic acid was used to treat rats with focal ischemic damage. Animals subjected to transient ischemia that were treated with dichloroacetic acid showed significant decreases in lactate concentration.

Animals↗
PubMed1998

Effect of temperature on the kinetics of lactate production and clearance in a rat model of forebrain ischemia.

To investigate the effect of brain temperature on metabolic perturbations during and following forebrain ischemia, localized 1H magnetic resonance spectroscopy was used to measure the kinetics of lactate production and clearance in a rat model of 12- or 20-min forebrain ischemia (two-vessel occlusion with hypotension) at a brain temperature of either 34.5 +/- 0.5 degrees C or 37.5 +/- 0.5 degrees C. During ischemia, lactate production was modeled with apparent first order kinetics. Hypothermia did not affect the rate or the extent of lactate production during ischemia. Upon reperfusion, a delay in the decrease of the cerebral lactate level was found in the normothermia groups. Such a delay was absent in hypothermia groups, which may reflect faster resumption of cerebral oxidative metabolism upon reperfusion in the hypothermic animals. The rate constant for lactate clearance postischemia was larger for normothermic animals and for the 20-min ischemia groups, perhaps because of increased blood-brain barrier permeability following more severe ischemia.

Animals↗
PubMed1998

The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease.

Progression of chronic renal failure in the Han:SPRD-cy rat polycystic kidney disease is associated with renal depletion of citric acid cycle metabolites and betaine. Amelioration of this disease by a soy protein diet is associated with retention of citric acid cycle anions, despite increased excretion, and preservation of tissue levels of betaine. As we have recently found that modest dietary supplementation with flaxseed preserves renal function and reduces histologic injury in the Han:SPRD-cy rat, we undertook a high-resolution 1H NMR spectroscopic study of urine and renal tissue extracts from Han:SPRD-cy rats to explore the renal biochemical consequences of a flaxseed diet. There was no significant dietary effect upon organic anion, methylamine, or osmolyte excretion in healthy animals. There was increased citrate excretion in Han:SPRD-cy rats fed flaxseed. Urinary ammonium excretion did not differ, suggesting that the observed increase in citrate excretion was not due to an alkaline effect of diet. Tissue extract studies revealed that disease amelioration was associated with tissue retention of succinate and betaine. Amelioration of Han:SPRD-cy rat polycystic kidney disease by diet is associated with alteration in the handling of citric acid cycle metabolites. Betaine may have a metabolic role in the reduction of chronic renal injury.

Animals↗
PubMed1998

Soy protein modification of rat polycystic kidney disease.

We undertook a study to determine whether soy protein feeding would ameliorate renal injury in the Han:SPRD-cy rat model of polycystic kidney disease (PKD). Male offspring of Han:SPRD-cy heterozygotes received isocaloric diets based on 20% casein or 20% heat-treated soy protein at weaning ad libitum for 8 wk. Soy-fed animals demonstrated lower serum creatinine (66 vs. 125 mumol/l; P = 0.002), lower urinary ammonium excretion (0.080 vs. 0.173 mmol/kg; P = 0.01), reduced renal cysts (0.98 vs. 4.92 ml/kg body wt, P < 0.0001), renal fibrosis (0.79 vs. 1.4 ml/kg; P = 0.016), macrophage infiltration, renal tubular cell proliferation, and apoptosis. Proton nuclear magnetic resonance (1H-NMR) studies of urine demonstrated that soy diet was associated with increased losses of citric acid cycle organic anions. 1H-NMR of perchloric acid-extracted tissue found that levels of succinate were not depleted in soy-fed animals, despite increased urinary losses. Soy-fed animals had marked elevation of tissue betaine (P < 0.001), with reduced taurine and cholines, compared with casein-fed animals (P < 0.001). Soy feeding dramatically reduces both tubular and interstitial pathology in the Han:SPRD-cy rat model of PKD, through mechanisms that remain to be determined.

Amines↗
PubMed1998

Intracerebral hemorrhage in the rat: effects of hematoma aspiration.

BACKGROUND AND PURPOSE: Deep intracerebral hemorrhage is associated with considerable mortality and morbidity, but the value of surgical therapy is debatable. The purpose of this study was to evaluate whether aspiration of the hematoma in a rodent model of intracerebral hemorrhage could improve final neurological outcome. METHODS: Intracerebral hemorrhage was induced in 2 groups of rats by injection of bacterial collagenase into the caudate nucleus. In 1 group of rats, streptokinase was used to lyse the hematoma 4 hours after hemorrhage induction, and the clot was then aspirated. Behavioral function was evaluated repeatedly until the rats were killed 7 weeks after collagenase injection. Histology was used to assess neuronal loss, astroglial proliferation, and overall brain morphology. In a second experiment, brain water was measured at 24 hours. RESULTS: The treated rats performed significantly better than controls on a motor-behavior evaluation on days 1, 2, and 28 after aspiration. Skilled forelimb testing performed for 3 weeks after the global behavior evaluations showed a significant deficit of contralateral forelimb function in both groups, but there was no significant difference between the 2 groups. Neuronal loss in the perihematoma striatum was significantly greater in untreated compared with treated rats. In most rats, structural damage extended into the internal capsule and thalamus. CONCLUSIONS: Aspiration of the hematoma after collagenase-induced hemorrhage slightly improved acute functional outcome and reduced neuronal loss from the striatum. Further studies are required to delineate the mechanism of the effect.

Animals↗
PubMed1997

Feline immunodeficiency virus causes increased glutamate levels and neuronal loss in brain.

Feline immunodeficiency virus, like human immunodeficiency virus type 1, is a retrolentivirus causing neurological disease and immune suppression. Primary neurological complications, including human immunodeficiency virus encephalopathy and peripheral neuropathy, and neuropathological changes, including gliosis, neuronal injury and multinucleated giant cells, have been described for human immunodeficiency virus type 1 infection. Excitatory amino acids have been implicated as a basis for human immunodeficiency virus encephalopathy and the accompanying neuronal injury. Here, we test our hypothesis that feline immunodeficiency virus infection results in glial activation accompanied by enhanced glutamatergic activity, causing neuronal loss. Neurological signs observed in naturally and experimentally infected animals included ataxia, aggressivity and reduced motor activity. Neuropathological changes included gliosis, perivascular cuffing and neuronal dropout in the brains of both experimentally and naturally infected animals, but not in uninfected animals. Feline immunodeficiency virus antigen and genome were detected in the brains of all experimentally and naturally infected animals. Proton nuclear magnetic resonance spectroscopy revealed significantly increased glutamate levels in the feline immunodeficiency virus-infected animals. In contrast, glutamate decarboxylase levels in GABAergic neurons were reduced in feline immunodeficiency virus-infected animals. These findings provide direct in vivo evidence for enhanced glutamate levels in conjunction with neuronal loss, supporting the hypothesis of glutamate-mediated neurotoxicity as a major mechanism in the neuropathogenesis of retrolentiviral infections.

Animals↗
PubMed1997

Altered organic anion and osmolyte content and excretion in rat polycystic kidney disease: an NMR study.

Polycystic kidney disease (PKD) is the fourth most common cause of end-stage renal disease and the most common potentially lethal inherited disease in humans. Early identification of carriers of dominant PKD in the absence of genetic markers is problematic in both humans and the Han:SPRD-cy/+ rat, a model of PKD that shares many features of human disease. We undertook a proton magnetic resonance imaging (MRI) study of young Han:SPRD-cy/+ and unaffected Han:SPRD(-)+/+ animals to determine whether carrier status could be identified based upon image appearance or signal characteristics. Affected animals demonstrated significant prolongation of longitudinal relaxation time (T1) and transverse relaxation time (T2) in both cystic renal cortex and noncystic renal medulla. Both of these measurements correlated significantly with whole kidney section tubular luminal space measurements, a correlate of water space, in the renal cortex, but only T1 in renal medulla showed a relationship to tubular luminal volume measured throughout the kidney. Urine and perchloric acid kidney extracts were studied using proton nuclear magnetic resonance (1H-NMR) spectroscopy to test the hypothesis that imaging differences implied specific urinary and tissue biochemical differences between affected and normal animals. 1H-NMR spectra of urine from cy/+ animals showed significantly increased excretion of alanine, citrate, succinate, and, 2-oxoglutarate but not methylamine compounds compared with +/+ animals. 1H-NMR spectra of aqueous perchloric acid kidney extracts confirmed reduced concentrations of the above ions and others involved in the citric acid cycle, as well the osmolytes betaine, taurine, and glycerophosphocholine PKD in the Han:SPRD-cy/+ rat is associated with distinct early MRI changes and alterations in urinary and tissue levels of organic anions and osmolytes.

Animals↗
PubMed1997

-(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia.

[(S)-Alpha-phenyl-2-pyridine-ethanamine dihydrochloride] (ARL 15896AR) is a low affinity uncompetitive N-methyl-D-aspartic acid receptor antagonist that was tested in animal models of anoxia and ischemia. Pretreatment of rodents with ARL 15896AR extended survival time during exposure to hypoxia. With the rat four-vessel occlusion model of global ischemia (20 min), oral dosing commencing at reflow, resulted in significant protection of the CA1 hippocampal neurons. ARL 15896AR was, however, ineffective in the rat two-vessel occlusion model and in the gerbil models of forebrain ischemia, the latter due to an inability to attain suitable plasma levels. In the spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) (2 hr plus 22 hr reflow), acute dosing with ARL 15896AR (i.p.) beginning from 30 min before or up to 1 hr post-MCAO significantly reduced cortical infarct volume. The ability of ARL 15896AR to influence infarct size, as well as functional correlates was examined in SHR after 90 min of MCAO. T2 weighted magnetic resonance images taken at 2 and 6 days post-MCAO revealed significantly smaller lesion sizes in the group receiving injections with ARL 15896AR beginning 30 min after occlusion. Spontaneously hypertensive rats were subsequently tested (30-42 days post-MCAO) and found to be deficient in skilled use of the forepaws (staircase test). The contralateral forepaw was most severely impaired, however, ARL 15896AR treatment prevented motor impairment in only the ipsilateral forepaw. Histopathological examination of cortical infarct size was unremarkable between treated and control rats. The findings indicate that ARL 15896AR exhibits neuroprotection in global and focal models of ischemia

Animals↗
PubMed1997

Biochemical changes in denervated muscle identified by magnetic resonance spectroscopy.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) has the potential to noninvasively delineate early biochemical changes in denervated muscle. In this study, we examine metabolic changes in denervated rat facial muscles using quantitative invitro 1H and 31P MRS. METHODS: Forty male Wistar rats were subjected to transection of the facial nerve trunk on the left and sham exposure on the right, and allowed to recover. The animals were then reoperated at 1, 2, 4, or 8 weeks after the initial procedure. EMG of the facial muscles and facial nerve conduction studies were performed at both time points, and facial muscles were harvested from normal and control sides at the second procedure. Perchloric acid extracts of facial muscles were then prepared for analysis using MRS. RESULTS: The results showed a progressive time-dependent decrease in Cr, PCr, Pi, ATP, and ADP all on the transected side. CONCLUSION: This study is an important step in the development of clinically relevant noninvasive methods of assessing and quantifying degeneration in nerve-muscle systems.

Adenosine Diphosphate↗
PubMed1996

Hippocampal neurons are damaged by caffeine-augmented electroshock seizures.

Caffeine-augmented electroconvulsive therapy has been introduced into medical practice without experimental confirmation that such seizure modification does not result in neuronal injury. In this report rats pretreated with caffeine prior to a series of nine electrically induced convulsions showed neuronal injury confined to hippocampal sectors and striatum. Electrically induced convulsions without caffeine pretreatment did not result in injury. The potential deleterious effects of caffeine augmentation of human electroconvulsive therapy require rigorous clinical assessment.

Animals↗
PubMed1996

Protective effect of dichloroacetate in a rat model of forebrain ischemia.

Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex (PDHC), and improves the recovery of cerebral pH, lactate, ATP, and PCr following reperfusion in animal models of forebrain ischemia. In order to determine whether this results in neuroprotection, rats were administered NaDCA (100 mg/kg or 10mg/kg i.v.) 10 min before 12 min of normothermic forebrain ischemia (bilateral carotid artery occlusion plus systemic hypotension, 45 mmHg). Neuronal injury assessed histopathologically 7 days post-ischemia was significantly reduced in the CA1 region of the hippocampus, the dorsal lateral striatum, and the neocortex, in rats treated with 100 mg/kg NaDCA, but not in rats treated with 10 mg/kg NaDCA.

Adenosine Triphosphate↗
PubMed1996

Neurochemical effects of static magnetic field exposure.

BACKGROUND: There has been considerable interest in both the lay and scientific media concerning the putative effects of exposure to electromagnetic fields. An assessment of the effects of static magnet exposure on neurochemistry was undertaken to determine potential risks to patients and staff involved with magnetic resonance imaging and spectroscopy. METHODS: One set of rats were exposed to weak static field (800 gauss [G]) in an otherwise normal laboratory surrounding. Another set of rats were exposed to 7-Tesla fields, both with suitable controls. RESULTS: Exposure of rats (n=8) to weak static fields for periods between 12 hours and 8 days produced no significant change in nighttime pineal or serum melatonin levels, as compared to controls, nor did it significantly influence levels of pontine medullary 5-hydroxytryptamine [5-HT] and hypothalamic 5-hydroxyindoleacetic acid [5-HIAA]. Placing rats in a 7-Tesla MRI magnet for 45 minutes produced similar results. CONCLUSIONS: These experiments suggest that daily light/dark cycle has much greater influence on levels of melatonin, catecholamines, serotonin, or their metabolites than does exposure to a static magnetic field.

Animals↗
PubMed1996

Experimental intracerebral hemorrhage in rats. Magnetic resonance imaging and histopathological correlates.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is associated with a considerable proportion of strokes and head injuries. The mechanism of brain cell injury associated with hemorrhage may be different from that due to pure ischemia. Therefore, it is essential that models of intracerebral hemorrhage be developed and well characterized. The purpose of this study was to obtain high-field MR images of rat brain at progressive times after induction of intracerebral hemorrhage and to correlate the images with behavior and histological evolution. METHODS: Intracerebral hemorrhage was induced in rats by injection of bacterial collagenase and heparin into the caudate nucleus. Histopathological changes and corresponding MR images were studied from 30 minutes to 3 weeks after injection. Behavioral changes were also followed for 3 weeks. RESULTS: Histological correlation showed that MR is capable of resolving the accumulation and degeneration of the hematoma, a centripetal wave of neutrophils infiltrating from the surrounding tissue beginning at 12 hours, and centripetal invasion of macrophages beginning at 48 hours. Widespread white matter edema was clearly evident on MR images for 1 week after the hemorrhage. Medium-sized striatal neurons were lost in the tissue surrounding the hematoma. Behavioral improvement was rapid during resolution of the edema but incomplete at 3 weeks. CONCLUSIONS: MR images correlate very well with histological changes in this experimental model of intracerebral hemorrhage and can therefore be used to follow changes due to drug treatments in vivo. The intense neutrophilic response to this lesion may contribute to neuronal injury at the periphery of the hematoma.

Animals↗