Effects of acute and long-term treatment of neonatal rats with
N-methyl-
d-aspartate (NMDA) receptor antagonists on changes in NMDA receptor properties were examined. Animals received either on ...postnatal day 6 a single dose of the antagonists MK-801 (1 mg/kg), or D-CPPene (2 mg/kg) or during the period from postnatal day 5 to 14, two daily injections of MK-801 (0.25 mg/kg) or D-CPPene (0.75 mg/kg). Control littermates received saline injections. In both cases animals were sacrificed one day after the last injection. NMDA receptor properties were examined in membrane preparations derived from the cerebral cortex by studying the modulation of
3HMK-801 binding by glutamate, Mg
2+ and D-CPPene. The density of agonist- and antagonist-binding sites in the CAI region of the hippocampus were determined by autoradiography, using
3HCGP39653 or
3Hglutamate as ligands. A significant developmental increase in NMDA receptor binding sites was detected both in preparations of cerebral cortical membranes and in the CAI area of the hippocampus. In addition, the Mg
2+ sensitivity of
3HMK-801 binding was significantly higher in membrane preparations from the cerebral cortex of postnatal day 15 compared to postnatal day 7 animals. Neither the single nor the subchronic treatment with NMDA receptor antagonists exerted a significant influence on the density of antagonist binding sites or on the modulation of
3HMK-801 binding by glutamate, Mg
2+ or D-CPPene. We conclude therefore that neonatal treatment with NMDA receptor antagonists
in vivo does not involve significant alterations in the properties and the densities of NMDA receptors in the brain regions studied, i.e., during the period when expression of these receptors is subject to pronounced developmental regulation.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An increased activity of the sympathetic nervous system is an important factor in the genesis of ventricular arrhythmias. Changes in average R-R interval, R-R interval variability (indirect measure ...of sympathovagal balance), occurrence of arrhythmias, and plasma norepinephrine concentrations were measured during a social stress episode (defeat) in two strains of rats, Wistar and wild type, which were supposed to differ in their autonomic stress responsiveness. Electrocardiograms were telemetrically recorded, and blood samples were withdrawn through jugular vein catheters from healthy, freely moving animals. R-R interval variability was estimated by the following time-domain parameters: the standard deviation of the mean R-R interval, the coefficient of variance, and the root mean square of successive differences in R-R interval. Average R-R interval and R-R interval variability measures, as well as plasma norepinephrine concentrations, indicated a higher sympathetic tone, a larger sympathetic responsiveness, and a lower parasympathetic antagonism after sympathetic activation in wild-type animals, which also showed a much higher incidence of arrhythmias (ventricular premature beats), compared with Wistar rats. These two strains might represent a valuable experimental model for studying the mechanisms (cellular/electrophysiological) responsible for the susceptibility to arrhythmias in healthy individuals exposed to stressful situations.
The vulnerability of the rat brain to intracerebrally injected
N-methyl-
d-aspartate (NMDA) drastically changes with age. We evaluated the developmental changes in the early and late responses to ...NMDA using
1H magnetic resonance imaging (MRI), cortical impedance and histology. NMDA, injected in the striatum of rats at postnatal days (P) 4, 7, 10, 14 and 21, induced a significant age-dependent reduction in the apparent diffusion coefficient (ADC) of tissue water in the striatum and the cerebral cortex monitored 1 h later using diffusion-weighted MRI. The reduction in ADC amounted 65% at P4 with lower values thereafter and was about 30% at P21. NMDA similarly induced a reduction in the cortical extracellular space (by 50% at P7 and 10% at P16) as measured with impedance recordings. The progressive decrease in the effect of NMDA with brain development was also indicated by a decrease in the volume of tissue in which the changes in ADC occurred (50 mm
3 at P4 and 8 mm
3 at P21). The diffusion of extracellular tracer molecules Mn
2+ or
3H-(
R)-α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) injected in the striatum and monitored with T
1-weighted MRI and autoradiography respectively showed a similar age dependence with the diffusion volume being twofold larger in P7 than in P21 brain. Thus restriction in diffusion during brain development may contribute to the decrease in NMDA-induced injury with age. The volume of tissue necrosis and gliosis, measured with T
2-weighted MRI and histology 5 days after NMDA injection, was similar to that outlined by the ADC reduction detected soon after the insult at P4, P7 and P21. However, at P10 and P14 only 50% of the tissue showing a hyperintense signal in DW images displayed necrosis and gliosis 5 days later. This study shows that during development the early response to NMDA in terms of cytotoxic cell swelling (indicated both with impedance recordings and diffusion-weighted MRI) decreases with age. In addition, with maturation only part of the brain tissue acutely affected by NMDA does proceed into necrosis and gliosis, indicating an increased capacity of cells in the developing rat brain to survive NMDA-induced cell swelling.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
274.
Eosinophils and cytokines Hansel, T T; Braun, R K; De Vries, I J ...
Agents and actions. Supplements,
1993, Volume:
43
Journal Article
Cytokines act on eosinophils to regulate eosinophil function, with IL-5 recognised to be especially important in control of eosinopoiesis, eosinophil survival and eosinophil priming. In addition, ...eosinophils have the capacity to produce cytokines involved in acute and chronic inflammatory and repair processes, as well as to produce cytokines that stimulate eosinophils within an autocrine loop. This paper describes (A) an immunomagnetic selection technique for the purification of human blood eosinophils, and (B) a method that employs immunofluorescence with flow cytometry for measurement of blood and sputum eosinophil surface markers. Having demonstrated that sputum eosinophils express HLA-DR, highly purified blood eosinophils were used to analyse (C) the induction and function of eosinophil HLA-DR. Cytokines have the capacity to induce eosinophil HLA-DR, and are produced by eosinophils as an accessory function during antigen presentation. Finally, preliminary data on (D) eosinophil production of IL-8 is presented. Hence, eosinophils have the capacity to act as immunomodulatory cells within cells networks in allergic and asthmatic inflammation.
