The ins and outs of the BCCAo model for chronic hypoperfusion: a multimodal and longitudinal MRI approach.

Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats.

A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease.

In vivo diffusion tensor imaging (DTI) was performed on the quinolinic acid (QUIN) rat model of Huntington's disease, together with behavioral assessment of motor deficits and histopathological characterization. DTI and histology revealed the presence of a cortical lesion in 53% of the QUIN animals (QUIN(+ctx)). Histologically, QUIN(+ctx) were distinguished from QUIN(-ctx) animals by increased astroglial reaction within a subregion of the caudate putamen and loss of white matter in the external capsula.

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism.

Purpose: Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [18F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB1) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D2 receptor availability and amphetamine-induced turning behaviour.

Methods: Twenty-one Wistar rats (11 QA and 10 shams) were investigated.

Putrescine as a marker of the effects of 2-chloropropionic acid in the rat brain.

The neurotoxin 2-chloropropionic acid (2CPA, 750 mg/kg, per os) induces ataxia in rats causing neuropathological changes (necrosis and edema) localized mainly in the cerebellum (CB). It has been described that putrescine (PUT) is a good marker of severe brain damage. We measured the concentration of PUT (by HPLC) in ataxic rat brains 3 days after 2CPA dosing.

Lesion of substantia nigra pars compacta by the GluR5 agonist ATPA.

Unlabelled: Dopamine (DA) released by substantia nigra pars compacta (SNc) neurons is a key regulator of motor activity. A deficiency in the striatum DA content due to SNc degeneration is a characteristic of Parkinson's disease. The involvement of excitotoxic mechanisms in this pathology has been suggested.

Extracellular putrescine content after acute excitotoxic brain damage in the rat.

We examined the effects of the local infusion of kainic acid (KA), by reverse dialysis in the rat striatum, on the concentration of polyamines in the extracellular striatal compartment and in tissue. KA infusion markedly increased (3-fold) extracellular putrescine (PUT) concentration, which reached its maximum at the end of the dialysis experiments (6 h). Tissue PUT concentration was also increased (2-fold) in the striatum perfused with KA but not in the contralateral side.

Cerebral distribution of polyamines in kainic acid-induced models of status epilepticus and ataxia in rats. Overproduction of putrescine and histological damage.

We study the brain regional distribution of putrescine after excitotoxic damage. After status epilepticus induced by kainic acid (9 mg/kg, i.p.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Regional distribution of lindane in rat brain.

Lindane distribution in brain areas after oral (30 mg/kg) and i.v.(0.