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C Feuerstein

Publications and source records attributed to C Feuerstein.

At least 37 records · Page 2Linked to original sources
PubMed1995

Long-term induction of tyrosine hydroxylase expression: compensatory response to partial degeneration of the dopaminergic nigrostriatal system in the rat brain.

The present study was undertaken to examine the adaptive changes occurring 1 and 6 months after moderate or severe unilateral 6-hydroxydopamine-induced lesions confined to the lateral part of the rat substantia nigra pars compacta (SNC). The expression of tyrosine hydroxylase (TH) enzyme was analyzed in the remaining dopaminergic nigral cell bodies and in the corresponding striatal nerve endings. In the cell bodies of the lesioned SNC, TH mRNA content was increased (+20 to +30%) 6 months after the lesion without changes in cellular TH protein amounts. The depletion of TH protein in the nerve terminal area was less severe than the percentage of cell loss observed in the SNC at 1- and 6-month postlesion intervals. Moreover, the decrease in TH protein in the ipsilateral striatum was less pronounced 6 months after lesion than 1 month after. That no corresponding change in TH protein content was observed in the cell bodies at a time when TH increased in nerve terminals suggests that the newly synthesized protein is probably rapidly transported to the striatal fibers. These results suggest the existence of a sequence of changes in TH expression between cell bodies and fibers, occurring spontaneously after partial denervation of the nigrostriatal pathway.

Adaptation, Physiological↗
PubMed1995

Brain noradrenergic systems modulate the ceco-colonic myoelectric activity in rats.

The role of the brain noradrenergic systems in the control of the ceco-colonic myoelectric activity was investigated in rats following lesions with intracerebroventricular (icv) or intracisternal (ic) injection of 6-hydroxydopamine (6-OHDA). Controls received the vehicle alone. The ceco-colonic myoelectric activity was recorded 3 weeks later in conscious rats chronically fitted with electrodes. After icv injection of 6-OHDA, lesions of rostral and caudal (spinal) noradrenergic systems were observed whereas only spinal noradrenergic systems were lesioned after ic injection. This differential pattern of lesions was followed by a differential pattern of ceco-colonic myoelectric activity. In fasted animals, a significant increase of the long spike burst (LSB) frequency (nb min-1) was observed after icv injection of 6-OHDA whereas no modification was observed after ic injection of the neurotoxic. After a 6-g pelleted rat diet, a significant increase of the LSB frequency was also observed in the icv lesioned group when compared to controls. No modification of the ceco-colonic noradrenergic innervation was observed, thus confirming the central selectivity of these lesions. Lesions of central noradrenergic systems modify the LSB frequency in rats; the rostral noradrenergic systems seem to play the major role.

Animals↗
PubMed1995

Deficits of cognitive executive functions in patients with sleep apnea syndrome.

Impairment of cognitive executive functions previously has been suspected to occur in association with sleep apnea syndrome (SAS), as suggested by some neuropsychological studies. However, such functions have not been assessed directly. In the present study, 17 patients with SAS were evaluated with various focused frontal lobe-related tests in comparison with 17 normal controls. Such tasks explored attention, short-term memory spans, learning abilities, planning and programming capacities, categorizing activities and verbal fluency. Patients were found to have a significantly decreased ability to initiate new mental processes and to inhibit automatic ones, in conjunction with a tendency for preservative errors. They were also affected with deficits of verbal and visual learning abilities and had reduced memory spans. Such defects were further evaluated via logistic regression against two criteria of the severity of the disease: the number of apneas and hypopneas per hour of sleep and the level of nocturnal hypoxemia. Memory deficits were rather related to the former, whereas typical frontal lobe-related abnormalities seemed rather consistent with the latter. These findings are discussed in light of data from the literature concerning cognitive impairments described for patients with isolated daytime sleepiness versus hypoxemia, as illustrated in other pathological or physiological circumstances.

Adult↗
PubMed1994

Normal distribution of alpha 2-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study.

The distribution of alpha 2 (alpha 2)-adrenoceptors along cervical, thoracic, lumbar, and sacral segments of the spinal cord of normal rats has been studied by quantitative autoradiography using the specific alpha 2-antagonist [3H]rauwolscine as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 2-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 2-adrenoceptor densities revealed the presence of these receptors throughout the whole gray matter with a preferential location in the superficial dorsal horn. This pattern was the same at all rostro-caudal levels of the cord and appeared very well correlated with the distribution of NA terminals revealed by immunohistochemistry, particularly in the superficial layers of the dorsal horn. After total transection of the spinal cord (caudally to the section) and 6-OHDA-induced lesion, an increase of alpha 2-adrenoceptor density was mainly observed within the distal dorsal horn thus evidencing supersensitivity in this area, while modifications were not detectable in other regions of the spinal gray matter, except at the lumbar level where other dorsal, central, and intermediate zones were significantly enriched.

Animals↗
PubMed1994

Evidence for dopamine D2 receptor mRNA expression by striatal astrocytes in culture: in situ hybridization and polymerase chain reaction studies.

The expression of dopamine D2 receptor mRNA in cultured rat striatal and cerebellar astrocytes was examined by in situ hybridization (ISH) and polymerase chain reaction (PCR). Cells double-labelled for glial fibrillary acidic protein (GFAP) immuno-histochemistry and dopamine D2 receptor mRNA (ISH) provide evidence that striatal but not cerebellar astrocytes express the dopamine D2 gene in vitro. These results were confirmed by polymerase chain reaction studies. As judged by GFAP immunostaining and morphology of the cells, this gene is almost exclusively expressed by astrocytes type 1. The expression of dopamine D2 receptor mRNA by striatal astrocytes in vitro, as found in this study, brings thus evidences for the existence of dopamine D2 receptors in such glial cells. This had been previously suggested from ligand binding studies but the typical dopaminergic nature of the binding to striatal astrocytes was left questionable. Our results with molecular biological techniques thus suggest that striatal dopamine might modulate the functions of striatal astrocytes.

Animals↗
PubMed1994

Effects of transection of the spinal cord in the rat: cystometric and autoradiographic studies.

Cystometric studies and autoradiographic experiments were performed in the rat to determine the urodynamic parameters and the cholinergic muscarinic binding properties of detrusor in control animals and those with complete spinal cord transection. After an unexplored spinal shock phase, the reactivity of the bladder was studied at 2, 5 and 9 weeks following transection. The chief modifications caused by spinal cord injury on the cystomanometric parameters were an increase of the maximal amplitude of contraction and a decrease of the pressure threshold. This correlated well with the results obtained in the autoradiographic studies, in which the density of muscarinic receptors in transected rats increased by 80% and 60% in the vesical sections after 2 and 5 weeks. The density of these muscarinic receptors sites returned to control levels 9 weeks after section.

Animals↗
PubMed1994

On time delay estimation of epileptic EEG.

The present study deals with comparative evaluation of various methods for time delay estimations applied to multichannel seizure EEG. The different methods included block algorithms, both in time and frequency domains (such as General Crosscorrelation, FFT, AR), and a new method for time delay estimation based on adaptive least-squares filtering. The various time delay estimators were tested on simulated signals and on real multichannel EEG recorded from rats having generalized seizures with focal onset. The adaptive least-squares filtering (the lattice-ladder type) has been found as the most efficient for time delay estimation.

Algorithms↗
PubMed1993

Intrastriatal transplants of embryonic dopaminergic neurons counteract the increase of striatal enkephalin immunostaining but not serotoninergic sprouting elicited by a neonatal lesion of the nigrostriatal dopaminergic pathway.

The aim of the our experiment was to compare the ability of intrastriatal implants of embryonic dopaminergic neurons to reverse two kinds of postlesion modification in the host brain: the change in the activity level of neurons in the denervated area and morphological modifications, e.g. collateral sprouting. The ascending dopaminergic system of 3-day-old rat pups was unilaterally lesioned by an intrahypothalamic injection of the neurotoxin 6-hydroxydopamine. This lesion has been described previously to induce an increase in the level of activity of striatal enkephalinergic neurons. The same lesion leads also to sprouting of the serotoninergic afferents in the striatum, leading to hyperinnervation of this structure. The existence of these modifications thus offers the possibility of testing the influence of grafts in one structure of the same animal on two lesion-induced reactions of different nature. A cell suspension obtained from mesencephali of embryonic day 14 rats and containing dopaminergic neurons was implanted into the denervated striatum of lesioned animals 5 days after the lesion. Nine months later the animals were killed and immunohistochemistry was performed on striatal sections using antibodies directed against tyrosine hydroxylase, methionine enkephalin and serotonin. Intensity of immunostaining (methionine enkephalin and serotonin) as well as innervation density (serotonin) was quantified through the use of a computer-assisted image analyser. The lesion led to the disappearance of striatal dopaminergic innervation. Implanted dopaminergic neurons were found scattered in the striatum and restored a dopaminergic innervation in a large portion of this structure. There was a marked increase in striatal methionine enkephalin immunostaining in lesioned animals, which was most pronounced in the dorsolateral part of the striatum (+ 150% compared to control values), while in the ventral part it was slight or non-existent. The density of striatal serotoninergic innervation was also increased by approximately 250% relative to control values. In grafted animals striatal enkephalin immunostaining was similar to that observed in control animals. On the other hand, the serotoninergic hyperinnervation was still present in the graft-bearing striata. These results suggest that while intrastriatal implants of embryonic dopaminergic neurons are able to counteract modifications in the functioning of local striatal neuronal systems such as the increase in enkephalinergic activity or receptor hypersensitivity occurring as a result of the lesion, they might be unable to reverse postlesion morphological modifications.

Animals↗
PubMed1993

Normal distribution of alpha-1-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study.

The distribution of alpha 1 (alpha 1)-adrenoceptors along the different segments of the spinal cord (cervical, thoracic, lumbar, and sacral) of normal rats has been studied by quantitative autoradiography using the specific alpha 1-antagonist [3H]Prazosin as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 1-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 1-adrenoceptor densities revealed a widespread distribution of these receptors along all segments of the spinal cord with a similar pattern in the various subregions of gray matter studied. This distribution of alpha 1-adrenoceptors was quite well correlated with the distribution of NA terminals, when referring to previous descriptions by immunohistochemistry. After 6-OHDA lesion, as well as caudally to the transection, a significant increase of alpha 1-adrenoceptor densities was observed in all spinal subregions thus evidencing supersensitivity. These results suggest that NA may act in the spinal cord, at least partly, via alpha 1-adrenoceptors and that the expression of these receptors could be influenced by NA dysfunction, as demonstrated here through the effects observed in lesioned animals.

Animals↗
PubMed1993

Time-course of changes in striatal levels of DA uptake sites, DA D2 receptor and preproenkephalin mRNAs after nigrostriatal dopaminergic denervation in the rat.

Changes in striatal dopamine uptake sites, D2 receptor and preproenkephalin (PPE) mRNA levels provoked by unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic (DA) pathway were studied by quantitative autoradiography and in situ hybridization (ISH) in rats sacrificed at different post-lesion delays. The disappearance of DA terminals as visualized with the labelling of dopamine uptake sites with [3H]GBR 12935 became significant 36 h after the lesion and was almost complete at a delay of 7 days. PPE mRNA amounts significantly increase (+24%) already at the shortest delay studied (9 h after the lesion) while the labelling of the uptake sites on DA terminals was not affected. The time course increase of PPE mRNA levels was progressive until 21 days post-lesion where it reached its maximum (+132%) and remained stable up to the latest delay studied (60 days). Conversely D2 mRNA contents remained unchanged up to 5 days post-surgery and then increased relatively quickly since at 7 days post-lesion their levels were near (+21%) the maximum observed which was reached at 21 days post-lesion (+32%). This study suggests a time-dependent differential sensitivity to the degree of DA denervation of both major components implicated in the striatopallidal output.

Animals↗
PubMed1993

Transplantation of fetal nigral cells reverses the increase of preproenkephalin mRNA levels in the rat striatum caused by 6-OHDA lesion of the dopaminergic nigrostriatal pathway: a quantitative in situ hybridization study.

Unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine (DA) pathway causes a significant increase of preproenkephalin (PPE) messenger RNA (mRNA) levels in the DA-depleted striatum in rat brain. Using an in situ hybridization (ISH) technique and computer-assisted microdensitometry, we quantified the changes in PPE mRNA levels in the striatum. Seven months after lesion, levels of PPE mRNA were 75% higher in the DA-depleted striatum than in the contralateral control striatum of the same animal or in the striatum of sham control animals. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a complete reversal of this increase and, in grafted animals, levels of PPE mRNA were at control values. Moreover, this reversal extended beyond the areas reinnervated by the grafted dopaminergic neurons.

Animals↗
PubMed1993

Cellular quantification of tyrosine hydroxylase in the rat brain by immunoautoradiography.

We developed a rapid and sensitive radioimmunohistochemical method for the quantification of tyrosine hydroxylase (TH) at both the anatomical and cellular level. Coronal tissue sections from fresh-frozen rat brains were incubated in the presence of a TH monoclonal antibody. The reaction was revealed with a 35S-labeled secondary antibody. TH content was quantified in catecholaminergic brain areas by measuring optical density on autoradiographic films or silver grain density on autoradiographic emulsion-coated sections. Regional TH concentrations determined in the locus ceruleus (LC), substantia nigra pars compacta (SNC), and ventral tegmental area (VTA) were significantly increased by 45% after reserpine treatment in the LC but unchanged in the SNC and VTA. Microscopic examination of TH radioimmunolabeling showed a heavy accumulation of silver grains over catecholaminergic cell bodies. In the LC, grain density per cell was heterogeneous and higher in the ventral than in the dorsal part of the structure. After reserpine treatment, TH levels were significantly increased (57%) in the neurons of the LC but not in those of the SNC or VTA. The data support the validity of this radioimmunohistochemical method as a tool for quantifying TH protein at the cellular level and they confirm that TH protein content is differentially regulated in noradrenergic and dopaminergic neurons in response to reserpine.

Animals↗
PubMed1992

Involvement of hypothalamic noradrenergic systems in the modulation of intestinal motility in rats.

Selective lesions of the noradrenergic systems of the paraventricular nucleus (PVN) of the hypothalamus with 6-hydroxydopamine (6-OHDA) lengthen the periodicity of the migrating myoelectric complex (MMC), an index of intestinal motility, in rats. These lengthening effects resemble those obtained after lesions of the locus coeruleus (LC), thus suggesting that noradrenergic terminals from LC to the PVN are involved in this modulation.

Analysis of Variance↗
PubMed1992

Autoradiographic localization of dopamine uptake sites in the rat brain with 3H-GBR 12935.

The regional distribution of dopamine (DA) uptake sites in the rat brain has been studied by quantitative autoradiography using [3H]GBR 12935 as a ligand. The binding of [3H]GBR 12935 to striatal sections was saturable and of high affinity (Kd = 1.6 nM); it occurred at a single population of sites and possessed the pharmacological features of the DA uptake sites. The highest densities of [3H]GBR 12935 binding sites were found in the caudate-putamen, nucleus accumbens, olfactory tubercle, ventral tegmental area and substantia nigra (especially in the pars compacta). Moderate levels of [3H]GBR 12935 binding were observed in globus pallidus, thalamus, hypothalamus, hippocampus, amygdala (basolateral nucleus) and prefrontal and singular cortices. This regional distribution of [3H]GBR 12935 binding closely correlated with the reported distribution of dopaminergic nerve terminals. The topographical distribution of [3H]GBR 12935 has also been studied in detail in striatal subregions and this distribution was compared, using quantitative TH immunoreactivity, to the density of striatal dopaminergic nerve terminals. There is good overlapping between these two regional distributions, the highest density of both markers was found in the lateral part of the striatum and a similar rostro-caudal gradient has been observed. A dopaminergic denervation caused a complete loss of [3H]GBR 12935 in basal ganglia ipsilateral to the lesion.

Animals↗
PubMed1992

Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: an autoradiographic study.

The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced hypersensitivity of striatal dopaminergic receptors. The ascending dopaminergic pathway of adult rats was unilaterally lesioned using 6-hydroxydopamine. Three weeks later a cell suspension obtained from the mesencephali of ED 14 rat embryos was implanted into the denervated striatum. Rotational responses to dopaminergic agonists were tested five months after implantation. One month later animals were killed and striatal dopaminergic receptor densities were quantified using autoradiography, the dopaminergic reinnervation of the host striatum being visualized with [3H]GBR 12935, a ligand labelling dopamine uptake sites. The lesion induced a behavioural hypersensitivity to dopaminergic agonists and lesioned animals displayed a strong rotation contralateral to the lesion in response to a test dose of the D1 agonist compound SKF 38393 (2.5 mg/kg) or of the D2 agonist LY 171555 (0.15 mg/kg). These responses were completely abolished by the graft. The normal distribution of D1 and D2 dopaminergic receptors in the rat striatum was similar to that described previously. Seven months after the lesion of the nigrostriatal dopaminergic pathway, the density of D1 receptors was not significantly affected while the density of D2 receptors was increased by about 25-50%. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a slight decrease of D1 receptor densities and to a reversal of the lesion-induced increase of striatal dopaminergic D2 receptors six months later. Moreover, this reversal concerned not only the reinnervated striatal region but also extended into non-reinnervated areas of the striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the density of dopaminergic D2 receptors.

Animals↗
PubMed1992

On the tracking of rapid dynamic changes in seizure EEG.

Estimation of autospectra and coherence and phase spectra of seizure EEG, using the FFT technique, will cause "smearing" of the rapid dynamic changes which occur during the seizure. This is inherent to FFT spectral estimation, due to the averaging process which is necessary in order to get consistent spectral estimates. A different approach suggested in the present study is to carry out multivariate autoregressive modeling of the multichannel seizure EEG, combined with adaptive segmentation. In order to obtain good estimates in cases of short record length, the vectorial AR modeling was based on residual energy ratios. The method has been tested on multichannel seizure EEG recordings from rats with focal epilepsy, caused by intracerebral administration of Kainic acid, and in depth EEG recordings in patients with temporal lobe epilepsy.

Animals↗