Quinolinic acid and GABA-B receptor ligand: effect on pyramidal neurons of the CA1 sector of rat's dorsal hippocampus following peripheral administration.

In this study we evaluated the effect of baclofen on excitotoxic action of quinolinic acid in hippocampus following its prolonged systemic administration in rats. Male Wistar rats, weighing 200-220 g, were used in the study. Quinolinic acid and baclofen were administered alone or together. Quinolinic acid was administered intraperitoneally (i.p.) in a dose of 60 mmol, baclofen in a dose of 2 mg/kg, by gastric tube, once daily for 8 days. The control group received 1 ml of saline i.p. once daily for 8 days. Quinolinic acid alone produced neurotoxic effect in the CA1 area of the hippocampal formation. The presence of the dark-degenerated pyramidal cells was a common sign of a delayed excitotoxic effect. Baclofen added to quinolinic acid markedly attenuated the neurotoxic effect of quinolinic acid. In such cases, only some dark degenerated cells were seen. Baclofen alone resulted in alterations in some pyramidal cells in the hippocampal formation.

Quinolinic acid and sigma receptor ligand: effect on pyramidal neurons of the CA1 sector of dorsal hippocampus following peripheral administration in rats.

Male Wistar rats, weighing 200-220 g, were used in the study. Quinolinic acid and racemic pentazocine were administered alone or together. Quinolinic acid was administered intraperitoneally (i.p.) in a dose of 60 mmol, racemic pentazocine intramuscularly in a dose of 2 mg/kg, once every 24 h for 8 days. The control group received 1 ml of saline i.p. once daily for 8 days. Pentazocine alone produced no signs of alteration in the hippocampal formation. Quinolinic acid produced neurotoxic effect in the CA1 area of the hippocampal formation. The presence of the dark-degenerated pyramidal cells was a common sign of a delayed excitotoxic effect. Pentazocine added to quinolinic acid markedly attenuated the neurotoxic effect of quinolinic acid. In such cases, only single dark degenerated cells were seen.

Histochemical and morphological evaluation of cerebral cortex of newborn rat in the course of joint ethanol and pyrazole administration.

The object of the study was the cerebral cortex of newborn rat. Tissue material was collected from the 2-nd to the 8-th hour after birth both from control animals and newborns whose mothers had been given both ethanol and pyrazole throughout gestation period, and also either ethanol alone or pyrazole. The drug were administered by gastric tube, in doses: ethanol 8.0 g/kg body weight, pyrazole 36 mg/kg body weight. Histochemical studies revealed variation in the intensity of reaction of the respiratory enzymes during examination of the cortex of newborns whose mothers had been fed with ethanol alone, or pyrazole alone. A strong inhibition of enzymatic reaction was observed in the examined cerebral cortex of newborns after a joint ethanol and pyrazole administration. Morphological studies showed an inhibition of maturing process of the cerebral cortex cells of animals treated with ethanol alone, whereas the cerebral cortex of animals whose mothers had been given both ethanol and pyrazole, presented symptoms allowing to diagnose encephalitis congenita symptomatica.

Thyroid C-cells in normal and goitrous gland: a histochemical study.

16 cases of goiter were examined for C-cells and 4 cases with normal thyroid gland. C-cells identification was based on masked metachromasia. There was stated both in toxic, atoxic goitrous tissue two forms of C-cells. The first characterized by positive metachromatic reaction and weak argyrophinty, the second type of C-cells were orthochromatic and argyrophilic. Metachromatic C-cells characterized as a rule by high alpha glycero phosphate menadione reductase as well succinic dehydrogenase and cytochrome oxidase.

Histochemical features of C-cell thyroid carcinoma.

Six cases of C-cell carcinoma of thyroid gland were studied applying histologic and histochemical methods as well as electron microscopy technique. A histologic feature of the carcinoma pattern was the diversity of pictures. Amyloid was commonly found in the carcinoma stroma. In some cells glycogen was present. Histochemically the carcinoma cells were marked by a strong activity of oxidative enzymes (GDH, SDH, LDH and MAO) as well as hydrolitic one (G-6-P and non specific enterases). Serotonin was found in two cases. An ultrastructural feature of carcinoma cells was the presence of cytoplasmic electron-dense, specific "endocrine type" secretory granules.

Effect of quinolinic acid administered during pregnancy on the brain of offspring.

The brains of rat offspring were histologically and histochemically examined after quinolinic acid administration to mothers during the gestation period. Quinolinic acid was administered intraperitoneally in a dose of 30 or 60 mmol, once daily, throughout the entire gestation period. Brain specimens were taken on days 1, 5, and 21 after birth from experimental and control animals. The neuronal cell body injury was detected in the selected brain formations. More profound alterations were seen in the substantia nigra and cerebral cortex, especially within the entorhinal area, whereas much less damage was noted in the striatum and hippocampus. Strongly pronounced symptoms of cerebral edema were seen. Histochemically, an increased activity of NADPH-reductase within neuronal cell bodies of the pyramidal layer in the hippocampus, striatum and cerebral cortex was demonstrated. The decrease of activity of succinic and alpha-glycerophosphate dehydrogenases within areas of tissue spongiosis was noted. The weak overall activity of MAO made it impossible to register changes in its intensity. No changes in the Ca-ATP-ase activity in brain formations after quinolinic acid treatment were observed. It has been reported that excitotoxic brain injury caused by quinolinic acid displays a selective pattern of neuronal degeneration that affects neuronal cell bodies but spares axons at the site of intracerebral injections (Schwarcz et al. 1983; Lehmann et al. 1985; Vezzani et al. 1986), as well as following systemic administration (Beskid and Markiewicz 1988; Beskid and Finiewicz-Murawiejska 1992). The excitotoxic activity of this compound can be detected by making use of the properties of the N-methyl-D-aspartate (NMDA) receptor agonist (Stone et al. 1987).(ABSTRACT TRUNCATED AT 250 WORDS)

Toxic effect of quinolinic acid administered during pregnancy on the cerebral cortex of rat's offspring: an ultrastructural study.

The cerebral cortex of rat's offspring was ultrastructurally examined after quinolinic acid administration to mothers during the gestation period. Quinolinic acid was administered intraperitoneally in a dose of 60 mmol, once daily, throughout the entire gestation period. Brain specimens were taken on day 5 after birth, from experimental and control animals. Ultrastructural analysis of the cortex tissue revealed maturing neuronal cell bodies and immaturelike cells. The distinguishing feature of altered maturing neuronal cell bodies was the presence of vacuoles and/or swollen cytoplasm. The vacuoles were present in the perikaryon as well as in the processes. As a rule, the organelles within swollen cytoplasm were scarce, and the cytoplasm itself had a distinctly lower electron density. In some cases a loss of chromatin grains was noted. The nuclear envelope was distended, forming perinuclearly situated channels and vacuoles. The most frequently observed change in the immature-like cells was a marked swelling of the cytoplasm, hence only few organelles could be seen. Only few synaptic complexes were present and their contact was weakly marked. The axon endings contained sometimes few vesicles. The postsynaptic dendritic processes were frequently significantly swollen. Astrocytes were swollen.

Quinolinic acid: effects on brain catecholamine and c-AMP content during L-dopa and reserpine administration.

The catecholamine content in rat brain tissue was determined following the administration of quinolinic acid alone or combined either with L-dopa and decarboxylase inhibitor or reserpine. Quinolinic acid alone decreased the levels of dopamine and noradrenaline, as well as those of c-AMP, and increased those of adrenaline. Treatment with L-dopa/decarboxylase inhibitor reversed the suppressing effect of quinolinic acid on dopamine, but not on noradrenaline. Reserpine alone depleted the contents of dopamine, noradrenaline and adrenaline. It could be concluded from the effects of quinolinic acid and reserpine given together that quinolinic acid suppresses the depletion of amines induced by reserpine. It has been demonstrated that quinolinic acid leads to injuries of nerve-cell bodies in pars compacta of the substantia nigra and in the striatum. Quinolinic acid is a natural metabolite of tryptophan, normally occurring in the liver, kidney and brain (Wolfensberger et al. 1983; Moroni et al. 1984). This compound exhibits convulsant and neuron excitant properties (Stone et al. 1987). It induces a selective pattern of neuronal degeneration both at the site of intracerebral injection (Schwarcz et al. 1983; Stone et al. 1987) and after general (intracardiac) administration (Beskid and Markiewicz 1988). The ability of quinolinic acid to produce neurotoxicity was greater in the striatum than in other parts of the brain. This prompted us to study catecholamine and c-AMP levels in rat brain tissue following quinolinic acid and L-dopa administration, as well as the influence of reserpine on quinolinic acid action.

The effect of quinolinic acid administered during pregnancy on the nigro-striatal complex of rat's offspring: ultrastructural investigation.

The nigro-striatal complex of rat's offspring was ultrastructurally examined after quinolinic acid administration to mothers during the gestation period, in order to mimick the congenital metabolic disturbances, resulting from an excess of quinolinic acid within foetal tissues. Hence, quinolinic acid was administered to mothers intraperitoneally in a dose of 60 mmol, once daily, throughout the entire gestation period. Brain specimens were taken on day 5 after birth, from experimental and control animals. Within the nigro-striatal complex there can be distinguished the more characteristic neuronal cell body alterations, and the more toxic effect as the edema signs and the retardment of the neuronal cell body maturity. In the substantia nigra, both swollen and dark-degenerated neuronal cell bodies have been identified, while in the striatum the latter forms predominated. The maturation of neuronal cell bodies was retarded, mainly within the striatum.

Quinolinic acid: effect on the nucleus arcuatus of the hypothalamus in the rat (ultrastructural evidence).

Quinolinic acid was administered intraperitoneally to male Wistar rats in a dose of 60 mmol, once daily for 8 days. By electron microscopy, in quinolinic acid-treated rats, the neuronal cell bodies in the arcuate nucleus had features of increased cellular activity, but some damage of neuronal cell bodies was also evident.

Histological and ultrastructural changes in the rat brain following systemic administration of picolinic acid.

Picolinic acid was administered intraperitoneally in a dose of 30, 60, or 100 mmol, once every 24 h for 8 days. Histologically, under normal conditions as well as when picolinic acid was administered in a dose of 30 mmol the brain formations exhibited characteristic features. When picolinic acid was administered in a dose of 60 mmol or 100 mmol, the alterations were profound and developed selectively in hippocampus, being much less intense in the substantia nigra and striatum. In such cases, injuries of neuronal cell bodies were accompanied by symptoms of spongiosis. Within the hippocampus, the neuronal cell body injury was selectively restricted to the hilar and CA3 regions of stratum pyramidale. Tissue spongiosis was more intense at the granular layer, particularly within the hilus and in the mossy fiber area at CA3. Histochemically, a variable intensity of the reaction of succinic and alpha-glycerophosphate dehydrogenases was demonstrated. A decrease in their activities was observed in areas where the neuronal cell body injuries and spongiosis took place. No changes in the Ca-ATP-ase activity in brain formation after picolinic acid treatment were observed. Ultrastructurally, the changes within substantia nigra were manifested by neuronal cell bodies of the dark type and dendritic degenerations. Also less damaged neuronal cell bodies were seen. They were swollen, depleted of polyribosomes with dilated elements of RER and altered mitochondria. Some of the dendritic profiles were swollen with lucent cytoplasm. Most of the boutons in synaptic contact zones were unchanged. Most presynaptic terminals which were in junction with dark dendrites were swollen with or without crystal-like aggregates of synaptic vesicles.

Effect of quinolinic acid administration on rat liver: ultrastructural investigation.

Quinolinic acid was administered intraperitoneally in a dose of 30 or 60 mmol, once every 24 h for 8 days. Its result in the dose of 30 mmol was the proliferation of smooth elements of the endoplasmic reticulum. The use of quinolinic acid in a dose of 60 mmol was characterized by the presence of more profound damage of organelles, among them the distinct decrease of the rough elements of the endoplasmic reticulum and polyribosomal structures was seen, and moreover, wide areas devoid of organelles were observed.