PubMed Health⌕ Search

Biomedical subjects

L Camón

Publications and source records attributed to L Camón.

16 recordsLinked to original sources
PubMed2001

Polyamine metabolism and glutamate receptor agonists-mediated excitotoxicity in the rat brain.

Putrescine (PUT) increases have been seen in a range of models of neuropathological disturbances. The present study was designed to compare the ability of various types of glutamate receptor agonist to promote excitotoxic brain damage and to examine whether a PUT increase is a general marker of excitotoxic brain damage. To that end, we evaluated features of brain damage associated with the excitotoxicity induced by both ionotropic glutamate receptor (iGluR) and metabotropic glutamate receptor (mGluR) agonists in the conscious rat and the changes produced in the regulation of polyamine metabolism. Intracerebroventricular infusion of N-methyl-D-aspartate (NMDA; 80 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 15 nmol), kainic acid (KA; 2.3 nmol), (R,S)-3,5-dihydroxyphenylglycine (3,5-DHPG; 1.5 micromol), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 2 micromol) produced similar seizure incidences (76-84%) in the rat. The convulsant episodes appeared sooner after iGluR (13-22 min) than after mGluR agonists (50-179 min). Histological analysis of the hippocampus 24 hr after seizures indicated several degrees of excitotoxic injury after equiconvulsive doses of the iGluR and mGluR agonists assayed. The agonists can be placed in the following order, according to the degree of damage they produce: AMPA > 3,5-DHPG approximately KA > NMDA > 1S,3R-ACPD. In the frontal cortex, moderate to low levels of damage were observed after all GluR agonists. Both iGluR- and mGluR-induced seizures produced an overshoot in the hippocampal and cortical PUT concentration, whereas spermidine and spermine levels were similar to control. Moreover, a concurrence of increased PUT levels and brain damage was observed, indicating that PUT is a general marker of excitotoxic brain damage.

Animals↗
PubMed2001

Polyamines in the basal ganglia of human brain. Influence of aging and degenerative movement disorders.

The distribution of polyamines in the human basal ganglia was examined, using dansyl-derivatives and high pressure liquid chromatography with fluorimetric detection. A heterogeneous distribution of putrescine, spermidine (SD) and spermine (SM) was observed in control brains. A consistent negative correlation between SD and SM content and age was found in different brain areas. These results suggest an involvement of polyamines in age-related changes occurring in white-matter. When the influence of degenerative movement disorders -Parkinson's disease, Huntington's disease (HD) and progressive supranuclear palsy- was analyzed, significant changes were observed only in HD, where a decrease in the concentration of SM was found in the putamen. These results suggest that in advanced stages of neurodegenerative processes, polyamines maintain their regulation. Only in the presence of severe atrophy, SM concentration is reduced.

Aged↗
PubMed1998

Long-term effects of status epilepticus induced by kainic acid on hippocampal polyamines.

Putrescine has been suggested to have an inhibitory effect on the excitability of the central nervous system. In the present study we found that 2 and 3 weeks after status epilepticus induced by kainic acid, rats had increased concentrations of putrescine (3- and 1.7-fold, respectively) and spermidine (1.6- and 1.4-fold, respectively) in the hippocampus. These animals exhibited a higher susceptibility to pentylentetrazol than the saline group. In addition, several hours after the pentylentetrazol injection, the concentration of putrescine and spermidine increased again in the brain and also in the plasma. In conclusion, increased hippocampal putrescine and spermidine concentrations seem to be linked with a lower threshold of excitability.

Animals↗
PubMed1998

Seizures and neuronal damage induced in the rat by activation of group I metabotropic glutamate receptors with their selective agonist 3,5-dihydroxyphenylglycine.

While it is well documented that the overactivation of ionotropic glutamate receptors leads to seizures and excitotoxic injury, little is known about the role of metabotropic glutamate receptors (mGluRs) in epileptogenesis and neuronal injury. Intracerebroventricular (i.c.v.) infusion of the group I mGluR specific agonist (R,S)-3,5-dihydroxyphenylglycine (3,5-DHPG) (1.5 micromol) to conscious rats produced severe and delayed seizures (onset at 4 hr) in 70% of the animals. The i.c.v. infusion of the group I mGluR non-selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (2 micromol) produced a similar rate of severe seizures, but with an early onset (0.6 hr). The analysis of motor activity showed that 3,5-DHPG elicited higher central stimulatory action than did 1S,3R-ACPD. Histopathological analysis of the hippocampus showed that 3,5-DHPG produced severe neuronal damage mainly in the CA1 pyramidal neurons and, to a lesser extent, in the CA3. Although 1S,3R-ACPD infusion also induced a slight injury of the CA1 and CA3 pyramidal neurons, damage was greater in the CA4 and dentate gyrus cells. In conclusion, the in vivo activation of group I mGluRs with the selective agonist 3,5-DHPG produces hyperexcitatory effects that lead to seizures and neuronal damage, these effects being more severe than those observed after infusion of the non-selective agonist 1S,3R-ACPD.

Analysis of Variance↗
PubMed1997

Changes in brain putrescine concentration associated with nonconvulsant behavioral patterns induced by systemic N-methyl-D-aspartate injection.

The relationship between the behavioral effects and motor activity induced by N-methyl-D-aspartate (NMDA) (150 mg/kg, ip) and brain polyamine concentration was studied in male Wistar rats. Motor activity was evaluated by an automated subtraction analysis system to measure the duration and vigor of any kind of movement. The behavioral modifications exhibited by the nonconvulsant NMDA-treated rats were evaluated according to the composition and sequence of behavioral components as: hypoactivity (pattern A), partially stereotyped activity (pattern B), and generalized stereotyped activity (pattern C). The concentration of polyamines in the frontal cortex and hippocampus was measured 8 and 24 h after drug injection. A relationship was found between the concentration of putrescine in both regions and the motor activity. In addition, the concentrations of putrescine also correlated with the vigor of the movements performed. Moreover, the putrescine concentration in the frontal cortex and hippocampus paralleled the behavioral patterns. The histological examination of the frontocortical and hippocampal areas did not reveal any evidence of damage. In conclusion, partially or generalized stereotyped activity elicited by systemic NMDA administration induces an increase in putrescine in the brain not linked to histological damage.

Animals↗
PubMed1996

Concentration of putrescine in plasma, frontal cortex and hippocampus of rats after systemic administration of the convulsants N-methyl-D-aspartate, pentylentetrazol, picrotoxinine, lindane and 4-aminopyridine.

The motor responses (such as stereotypic behavior or convulsions induced in rats by N-methyl-D-aspartate (NMDA) administered systemically were followed by a rapid, moderate increase in the putrescine concentration in plasma which preceded an increase in this amine in the brain. This effect was not observed following the convulsions evoked by pentylentetrazol, picrotoxinine, lindane or 4-aminopyridine. However, all the convulsants assayed induced a mild increase in the concentration of putrescine in the frontal cortex and hippocampus. A differential activation of the ornithine decarboxylase (ODC)/polyamine system in both cerebral and peripheral tissues could account for these results.

Aminopyrine↗
PubMed1995

Blood polyamines in the rat.

The physiological concentrations of polyamines in plasma, serum and red blood cells were determined in male Wistar rats, using HPLC with fluorometric detection. The analysis of the metabolic ratio between polyamines and the frontal cortex/plasma relationship for putrescine, spermidine and spermine, suggest the existence of common mechanisms in the regulation of spermidine in blood and brain.

Animals↗
PubMed1994

On the neurotoxicity of systemically administered putrescine: influence of kinetic factors.

Putrescine (PUT) given ip to male rats produced a dose-dependent behavioural response. The observed signs were mainly shaking behaviour and motor disorders. The severity of the motor signs closely correlated with cortical PUT levels. After [14C]-PUT, the levels of related radioactivity ([14C]-PUTrr) in frontal cortex paralleled the levels of tracer in blood. Furthermore, the levels of tracer in blood and in frontal cortex were higher in the animals with toxicity signs than in non-affected ones. The frontal cortex levels of polyamines determined by HPLC revealed that only PUT paralleled the severity of the clinical status of the rats. No modifications of spermidine (SD) or spermine (SM) content were detected. Two hours after [14C]-PUT administration, only about 30% of the cortical [14C]-PUTrr was analyzed as PUT itself and no radioactivity was detected as SD and SM. Our results suggest that the radioactivity not associated to PUT could be related to more polar metabolites than SD or SM as acetylated derivatives.

Animals↗
PubMed1993

Lindane administration to the rat induces modifications in the regional cerebral binding of [3H]Muscimol, [3H]-flunitrazepam, and t-[35S]butylbicyclophosphorothionate: an autoradiographic study.

The effect of lindane administration on the specific binding of ligands to different sites on the GABAA receptor-ionophore complex was studied in the rat brain by receptor mapping autoradiography. [3H]Muscimol (Mus), [3H]flunitrazepam (Flu), and t-[35S]butylbicyclophosphorothionate (TBPS) were used as specific ligands of GABA, benzodiazepine, and picrotoxinin binding sites, respectively. Rats received a single oral dose of 30 mg/kg lindane and they were classified into two groups according to the absence or presence of convulsions. Vehicle-treated groups acted as controls. The effect of the xenobiotic on ligand binding was measured in different brain areas and nuclei 12 min or 5 h after its administration. Lindane induced a generalized decrease in [35S]TBPS binding, which was present shortly after dosing. In addition, [3H]Flu binding was increased in lindane-treated animals, this modification also appearing shortly after administration but diminishing during the studied time. Finally, lindane induced a decrease in [3H]Mus binding, which became more evident over time. These modifications were observed both in the presence and in the absence of convulsions. However, an increase in [3H]-Mus binding was detected shortly after lindane-induced convulsions. The observed decrease in [35S]TBPS binding is in agreement with the postulated action of lindane at the picrotoxinin binding site of the GABAA receptor chloride channel. The effects observed on the binding of [3H]Flu and [3H]Mus may be secondary to the action of lindane as an allosteric antagonist of the GABAA receptor.

Animals↗
PubMed1989

Regional changes in brain 2-14C-deoxyglucose uptake induced by convulsant and non-convulsant doses of lindane.

Lindane-induced dose- and time-related changes in regional 2-14C-deoxyglucose (2-DG) uptake were examined in 59 discrete rat brain structures using the 2-DG autoradiographic technique. At different times (0.5-144 hr) after administration of a seizure-inducing single dose of lindane (60 mg/kg), 2-DG uptake was significantly increased in 18 cortical and subcortical regions mainly related to the limbic system (e.g., Ammon's horn, dentate gyrus, septal nuclei, nucleus accumbens, olfactory cortex) and extrapyramidal and sensory-motor areas (e.g., cerebellar cortex, red nucleus, medial vestibular nucleus). There was also a significant increase in superior colliculus layer II. In addition, significant decreases occurred in a group of 6 regions (e.g., auditory and motor cortices). Non-convulsing animals treated with the same dose of lindane showed a regional pattern of 2-DG uptake less modified than the convulsant group. A non-convulsant single dose of lindane (30 mg/kg) also modified significantly the 2-DG uptake (0.5-24 hr) in some brain areas. Although the various single doses of lindane tested produced different altered patterns of brain 2-DG uptake, some structures showed a similar trend in their modification (e.g., superior colliculi and accumbens, raphe and red nuclei). Repeated non-convulsant doses of lindane produced defined and long-lasting significant elevations of 2-DG uptake in some subcortical structures (e.g., dorsal cochlear nucleus, dentate gyrus). Considering the treated groups all together, 2-DG uptake increased significantly in 26 of the 59 regions examined but only decreased significantly in 9 of them during the course of lindane effects. This fact can be related to the stimulant action described for this neurotoxic agent. The observed pattern provides a descriptive approach to the functional alterations occurring in vivo during the course of lindane intoxication. These results may be linked to the proposed mechanism of lindane neurotoxicity postulating an initial action on the GABAA receptor-chloride channel sites.

Animals↗
PubMed1988

Cerebral glucose uptake in lindane-treated rats.

The pesticide and ectoparasiticide lindane, gamma-isomer of hexachlorocyclohexane, is a powerful CNS-stimulant inducing convulsions and other signs of hyperexcitability in mammals. The present work was carried out to investigate the effect of lindane on brain regional glucose uptake at convulsant and non-convulsant doses. Local glucose uptake was measured in male Wistar rats using a modification of the 2-deoxyglucose (2-DG) method. Animals received i.p. [3H]2-DG and the amount of label in different brain structures of control and lindane-treated animals was assayed by a liquid scintillation counting of 18 dissected regions. Lindane at single convulsant dose (150 mg/kg, p.o.) increased 2-DG uptake in olfactory tubercules, hypothalamus, hippocampus, parafloculi and hypophysis. The uptake was decreased in parietal cortex, thalamus and pons-medulla. The pattern of 2-DG uptake after a single non-convulsant dose of 30 mg/kg p.o. was not so modified. After 1 week of treatment with 10 mg/kg per day p.o., increased 2-DG uptake was observed in superior colliculi while it was decreased in parietal cortex. The increase of 2-DG uptake in limbic regions observed at the convulsive dose agrees with the experimental association between poisoning signs induced by lindane and damage in the limbic system.

Animals↗
PubMed1988

The effect of non-convulsant doses of lindane on temperature and body weight.

The effect of lindane (gamma-HCH) on temperature, food intake and body weight was studied in male and female rats after single or repeated non-convulsant oral doses. A single dose of 30 mg/kg induced a significant decrease of core temperature (0.4 degrees C in males and 0.66 degrees C in females) 5 h after administration when compared to the control value. Lindane-induced hypothermia was strongly potentiated (1.45 degrees C) by cold stress when rats were kept at 4 degrees C. The same dose of lindane produced a significant decrease in body weight gain (-85% in males and -219% in females compared to the control gain), accompanied by a diminution of food intake, 24 h after administration. No decrease in both parameters was observed when alpha- or delta-HCH isomers 30 mg/kg were tested. After daily administration with 10 mg/kg lindane for 7 days, no hypothermic effects were observed. However, a slight but significant decrease in body weight gain was recorded over the treatment period. This effect was also accompanied by a reduced food intake. The observed stereoselective effects of HCH isomers on core temperature and body weight could be a useful model to study the mechanisms of lindane neurotoxicity at low subconvulsant doses.

Animals↗
PubMed1988

Synthesis and utilization of neurotransmitters: actions of subconvulsant doses of hexachlorocyclohexane isomers on brain monoamines.

We have developed a model for the treatment of data of concentration of brain neurotransmitters (particularly serotonin and the catecholamines), in which the changes induced by any given treatment on the neurotransmitter (NT) and its main metabolite (ME) are converted into 2 new parameters named S and U, that are related to the modifications in the synthesis (S) and utilization (U) of the neurotransmitter elicited by the treatment. Using this model we have studied the effect of subconvulsant doses of lindane and other hexachlorocyclohexane isomers (alpha, beta and delta) on brain monoaminergic systems. The results obtained indicate that serotonergic activity is increased in cell bodies (dorsal raphe) as well as in regions rich in nerve terminals after treatment with lindane. Also, the activity of dopaminergic neurons is increased in the substantia nigra. These results are in agreement with the proposed role of lindane as a "picrotoxinin-like" substance acting as an antagonist at the GABA-A receptor complex and thus impairing the inhibitory tone exerted by GABA on a variety of neurons (serotonin in raphe nuclei and dopamine in substantia nigra).

Administration, Oral↗
PubMed1988

Brain metabolites of lindane and related isomers: identification by negative ion mass spectrometry.

The application of a new method of gas chromatography-mass spectrometry (GC-MS) to the study of some aspects of the metabolism of hexachlorocyclohexanes is presented. Instead of the classical mode of ionization (Electron Impact, EI), this method uses chemical ionization, recording only the negative ions produced. This enables a tremendous enhancement of the signal when chlorinated compounds elute from the chromatographic column. The mass spectra obtained consist generally in the ions corresponding to the molecular weight of the compound analyzed. The sensitivity of the method is higher than any other GC method described: the limit of detection of several organochlorine compounds can be as low as 60 femtograms. Using this method we have been able to identify several Lindane metabolites (tetra-, penta- and hexachlorocyclohexenes, tetra- and pentachlorobenzene) in rat brain homogenates without any purification step. Using this method, a quantitative study of the main metabolites found in brain after treatment with 4 different HCH isomers has been performed. This study reveals that the HCH isomers are cleared from the brain via different metabolic pathways, with a rate of production of metabolites which is inversely correlated to their half lives in brain.

Administration, Oral↗
PubMed1988

Regional distribution of lindane in rat brain.

Lindane distribution in brain areas after oral (30 mg/kg) and i.v.(0.3 mg/kg) administration was studied using autoradiography-imaging analysis and dissection-liquid scintillation counting techniques. Both experimental approaches gave similar results. An heterogeneous distribution of lindane-label in brain regions was observed. Radiolabel concentration in white matter was higher than in grey matter and the concentration ratio was time increasing. Higher concentrations of lindane-label were found in thalamus, mid-brain and pons-medulla at different times after administration when compared to the whole brain mean value. Pretreatment with 300 mg/kg of the alpha-HCH isomer did not induce significant modification in the pattern of lindane radioactivity distribution in brain. Lindane affinity for white matter and myelinated structures could be related to its lipophilic behaviour and is not in disagreement with the current proposed mechanism of action for this xenobiotic.

Administration, Oral↗