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F Filloux

Publications and source records attributed to F Filloux.

At least 19 recordsLinked to original sources
PubMed1999

Unilateral hypoxic-ischemic injury in the neonatal rat brain evaluated by in vivo MRI. Correlation with histopathology and neuroprotection by MK-801.

RATIONALE AND OBJECTIVES: MRI was used for the in vivo evaluation of unilateral hypoxic-ischemic brain injury and the evaluation of MK-801 in the neonatal rat. METHODS: T2-weighted scans were obtained during the acute phase of HI injury and 3 months later. Histology was performed to correlate MRI signal changes with pathology. Finally, the effectiveness of MK-801 to limit brain injury was regionally assessed in vivo using T2-weighted MRI. RESULTS: Injury visualized by MRI at 72 hours after hypoxia correlated strongly with histopathologic analysis. Transient injury was identified. MK-801 significantly reduced the lesion extent at the level of the hippocampus. Patterns of unilateral versus bilateral neonatal brain injury were found to differ. CONCLUSIONS: The study demonstrates unique patterns of brain injury not seen in adult animal hypoxia-ischemia studies, and the sensitivity of the corpus callosum to hypoxia-ischemia. MK-801, although neuroprotective, did not offer any selective neuroprotective benefit.

Animals↗
PubMed1998

Magnetic resonance imaging of hypoxic-ischemic brain injury in the neonatal rat.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging was used for the in vivo evaluation of bihemispheric hypoxic-ischemic (HI) injury in the neonatal rat. METHODS: Seven-day-old rats underwent sham surgery (n = 7) or bilateral carotid artery ligation and hypoxia (30-45 min) (n = 8). T2-weighted imaging was used to study the temporal evolution of injury. Histopathology was used to correlate injury with MR signal changes. RESULTS: T2-weighted images exhibited considerable anatomic detail (0.2 mm resolution in-plane). The cortex, dorsolateral striatum and thalamus were affected, while the hippocampus was spared. Magnetic resonance signal change was seen as early as 1.5 hrs post-HI (lesion extent, 27%-39%), and reached a maximum at 48 hrs (37%-49%). Magnetic resonance imaging estimation of injury at 72 hours after HI was compared with histopathology and correlated well (r = 0.98). CONCLUSIONS: The study demonstrates the feasibility of magnetic resonance imaging for in vivo evaluation of neonatal brain injury and that vulnerability in the neonatal hippocampus is strikingly different than in adult HI models.

Age Factors↗
PubMed1998

Inhibitory deficits in Tourette syndrome: a function of comorbidity and symptom severity.

This study examined central inhibitory function in children with Tourette syndrome (TS; N = 46) and normally developing controls (N = 22) matched on age, gender, and IQ. A negative priming task measured the ability to inhibit processing of irrelevant distractor stimuli presented on a visual display. Initial analyses indicated that participants with Tourette syndrome did not differ significantly in inhibitory function from controls. However, when the large Tourette syndrome sample was separated into subgroups, one without evidence of comorbidity (N = 23) and the other meeting research criteria for either AD/HD, OCD, or both (N = 23), it became evident that individuals with Tourette syndrome with comorbid conditions tended to perform less well than the control group, whereas those without comorbidity performed much like controls. Similarly, when the large Tourette syndrome sample was divided into two subgroups on the basis of severity of symptomatology (N = 23 in each), those with more numerous and severe symptoms of Tourette syndrome, AD/HD, and OCD performed significantly less well than both controls and Tourette syndrome subjects with fewer and less severe symptoms. This suggests that neuropsychological impairment occurs as a function of comorbidity and symptom severity in Tourette syndrome. It also suggests that categorical diagnoses alone may be less useful than dimensional methods for predicting cognitive impairment in individuals with Tourette syndrome.

Adolescent↗
PubMed1996

Bilineal transmission and phenotypic variation of Tourette's disorder in a large pedigree.

OBJECTIVE: Variability in the clinical phenotype of Tourette's disorder (TD) was assessed in a single large family, with a focus on the influence of bilineal transmission. METHOD: Tics, obsessive-compulsive symptoms, and attention-deficit symptoms were evaluated through interview and standardized checklists for 175 descendants and 16 spouses who married into a single four-generation pedigree. RESULTS: Some form of tic disorder was diagnosed in 67% of descendants and 44% of married-in spouses. TD was found in 36% of descendants and in 31% of married-in spouses. Impairment was minimal in most cases, but age at onset and location and number of tics were typical of TD described in clinic samples. Obsessive-compulsive symptoms were found in 38% of descendants and 62% of those with current TD, but obsessive-compulsive disorder was found in only four individuals. Attention-deficit hyperactivity disorder occurred in 25% of children. Multivariate analysis indicated that offspring of two parents with tic disorders manifested significantly more lifetime tics, more severe categories of tic disorders, and an earlier age at onset for TD compared with offspring of one or no affected parents. CONCLUSIONS: TD in this family is most often a mild disorder but otherwise similar to published clinical cases. Increased morbidity is significantly associated with bilineality. The frequency and impact of bilineality raise questions about possible assortative mating, the prevalence of TD, and assumed mechanisms of transmission and etiology.

Adolescent↗
PubMed1995

Intermediate inheritance of Tourette syndrome, assuming assortative mating.

Segregation analysis incorporating assortative mating was used to test for major locus inheritance of Tourette syndrome in a single large pedigree containing 182 members. The analysis provided evidence of a major locus with an intermediate inheritance pattern for which the penetrance was estimated from the data as 28% in heterozygotes and 98%-99% in homozygotes. A significant assortative mating correlation was estimated from the data as 70%-79%. In contrast, when assortative mating was not included in the model, intermediate inheritance was not inferred. If, in addition, constancy of the allele frequencies across generations was not assumed, Mendelian transmission was rejected. Each subject, affected or unaffected, was assigned a score reflecting the presence and severity of symptoms. Higher means scores in affected homozygotes than in affected heterozygotes suggested greater severity in homozygotes: genotype information was obtained from genotype probabilities computed assuming intermediate inheritance.

Adolescent↗
PubMed1994

Effect of neonatal hypoxia-ischemia on nigro-striatal dopamine receptors and on striatal neuropeptide Y, dynorphin A and substance P concentrations in rats.

Perinatal hypoxic-ischemic brain injury was induced in 7- to 8-day-old rats by ligating the left carotid artery with subsequent exposure to 9% oxygen atmosphere for 2.5 h. The animals were killed 7 days later and grouped according to the degree of brain injury sustained after hypoxia-ischemia. Total protein content measured in striatum ipsilateral to the ligation, and dissected from brains showing extensive damage, was reduced to 64% of contralateral tissue. The protein content was not altered in other groups including control animals exposed to air and in sham-operated animals exposed to hypoxic conditions. The concentration of (pg/mg protein) and total (pg/striatum) striatal dynorphin A-like immunoreactivity (DLI) from brains with extensive damage were increased to 481% and 285% of the contralateral side, respectively. Hypoxia-ischemia increased striatal neuropeptide Y-like immunoreactivity (NPYLI) concentration from brains with extensive damage to 157% of contralateral side, but when the results were expressed as total NPYLI content per striatum, NPYLI content in striatum with extensive damage remained unaltered. Substance P-like immunoreactivity (SPLI) concentration and total content per striatum from brains with extensive damage were reduced to 66% and 43% of the contralateral side, respectively. D1 and D2 receptor density in animals killed 10 days after injury was reduced by 24% and 22% of control, respectively, in striatum from brains with extensive damage. These results indicate complex changes in brain neuropeptides following neonatal hypoxia-ischemia. Damage in the substance P system could have functional effects on dopaminergic transmission while the increase in NPYLI and in DLI concentrations may respectively reflect the relative preservation from neuronal damage and possibly an increase in neuropeptide synthesis or decrease in release. The decrease in SPLI concentration and the increase DLI concentration induced by hypoxia-ischemia suggests that these peptides may be present in separate neurons.

Aging↗
PubMed1994

The distribution of omega-conotoxin MVIICnle-binding sites in rat brain measured by autoradiography.

An analogue of omega-conotoxin MVIIC, [125I]omega-MVIICnle, has been employed in an autoradiographic assay to define the distribution of binding sites in rat brain of this neuronal calcium channel antagonist. In comparison with N-type channels (labeled by [125I]omega conotoxin GVIA), omega-MVIICnle sites are much denser in cerebellum (molecular layer) than in forebrain. Binding in thalamus is also comparatively high for omega-MVIICnle. Under these conditions, [125I]omega-MVIICnle binding to rat brain sections is not displaceable by the N-channel antagonist, omega-conotoxin GVIA. The calcium channel blocker [125I]omega-conotoxin MVIICnle labels a unique set of binding sites in mammalian brain.

Animals↗
PubMed1994

Complex patterns of [125I]omega-conotoxin GVIA binding site expression during postnatal rat brain development.

In the mature CNS, N-type calcium channels regulate neurotransmitter release. The role of these channels in developing brain is less clear. Study of [125I]omega-conotoxin GVIA binding sites in developing rat brain using autoradiography reveals that putative N-type channels appear and disappear in complex temporal-spatial profiles including: (1) gradual increase to adult levels (cerebral cortex); (2) substructure differentiation (cerebellum); (3) transient expression (pons); and, (4) selective depletion (medulla). Transient expression of N-type calcium channels may influence specific neurodevelopmental processes.

Aging↗
PubMed1994

Executive function abilities in autism and Tourette syndrome: an information processing approach.

This study used information processing paradigms to provide a detailed examination of executive function abilities in autism. The performance of non-retarded autistic children was compared with that of two matched control groups, one with Tourette Syndrome and the other developmentally normal. Autistic subjects performed as well as controls on tasks requiring global-local processing and inhibition of neutral responses. In contrast to both control groups, however, the autistic sample was significantly impaired on a measure of cognitive flexibility. The performance of children with Tourette Syndrome did not differ from that of normal controls on any task. These results refine our knowledge about executive dysfunction in autism and suggest a new conceptual framework and general method for investigating the cognitive underpinnings of neurodevelopmental disorders.

Adolescent↗
PubMed1993

Pre- and postsynaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection.

Considerable evidence indicates that dopamine (DA) may play a neurotoxic role in brain in certain pathologic circumstances. To investigate this issue, dopamine (1000 nmol/1 microliter) was directly injected into the striatum of anesthetized Sprague-Dawley rats. Control animals received equal-volume injections of gamma-aminobutyric acid (GABA) or NaCl at identical concentrations (diluted in distilled H2O, pH 7.0-7.7). Brains were removed 7 to 9 days later and frozen or fixed and sectioned for histologic and autoradiographic analysis. Dopamine injection resulted in a small-volume (3.3-mm3) lesion in comparison to control GABA and NaCl injections which produced only a needle track < 0.6 mm3 in volume (P < 0.01). Dose dependency of DA toxicity was demonstrated, with substantial parenchymal damage requiring an injection of 500 nmol/1 microliter. Within the lesion, marked neuronal loss, macrophage invasion, and capillary and glial proliferation were present. Acetylcholinesterase staining and D1 receptor binding were markedly reduced as well. [3H]RO5-4864 binding to peripheral benzodiazepine receptors (on astrocytes) was increased in the periphery of the lesion. The binding of 1-[3H]benzo[b]cyclohexylthiophenylpiperidine to dopamine uptake sites was also reduced, but over a wider striatal area in comparison to local parenchymal damage. Prior interruption of the dopaminergic nigrostriatal pathway (by injection of 6-hydroxydopamine) appeared to potentiate the toxicity of intrastriatal dopamine injection. The findings indicate that local injection of dopamine produces both post- and presynaptic damage to nigrostriatal structures, and support the contention that dopamine may act as a low-potency neurotoxin.

Animals↗
PubMed1992

Autoradiographic localization of the binding of calcium channel antagonist, [125I]omega-agatoxin IIIA, in rat brain.

The calcium channel antagonists omega-agatoxin IIIA (omega-Aga-IIIA) and omega-conotoxin GVIA (omega-CgTx) were radioiodinated and used to locate binding sites in the rat brain by receptor autoradiography. While patterns of regional binding to sagittal sections of rat brain were generally similar for the 2 toxins, notable differences in the cerebellum and hippocampus were observed. Specific [125I]omega-Aga-IIIA binding was greatest in the granule cell layers of the cerebellum and of the dentate gyrus. In contrast, binding of [125I]omega-CgTx was most intense in the molecular layers of these structures. Less than one-third of [125I]omega-Aga-IIIA binding in rat brain slices was inhibited by pre-exposure to 250 nM omega-CgTx, while 40 nM omega-Aga-IIIA virtually eliminated the binding of [125I]omega-CgTx under the same conditions. The P-type calcium channel antagonist omega-Aga-IVA blocked only a small fraction of [125I]omega-Aga-IIIA and [125I]omega-CgTx binding. These autoradiographic data are consistent with membrane binding experiments and indicate that the combined use of agatoxins and conotoxins may be useful in the characterization of separate types of neuronal calcium channels.

Agatoxins↗
PubMed1992

Effects of hypoxic-ischemic brain damage on dopaminergic markers in the neonatal rat: a regional autoradiographic analysis.

Dopamine has been implicated as an endogenous substance that may mediate neuronal death after hypoxic-ischemic insult. Using semiquantitative autoradiography, we studied the effect of perinatal hypoxic-ischemic injury on dopamine binding sites in rat brain. Experimental injury resulted in a substantial decrease in dopamine type-1 (D1) and forskolin (adenylate cyclase) binding sites. In contrast, markers for dopamine type-2 (D2) sites and for dopamine uptake were unaffected in lesioned animals. Changes within dopaminergic pathways were variable, with reduction in binding being encountered mainly in components of the extrapyramidal motor system: caudate-putamen, -61%; globus pallidus, -64%; entopeduncular nucleus, -60%; and substantia nigra, -69%. Furthermore, the topography of D1 receptor loss within the caudate-putamen was not uniform, with the greatest decrement in dorsolateral regions. Reduced D1 versus D2 receptor activation may underlie extrapyramidal movement disorders that appear as a consequence of perinatal hypoxic-ischemic insult.

Animals↗
PubMed1991

Dopaminergic modulation of excitotoxicity in rat striatum: evidence from nigrostriatal lesions.

Considerable evidence indicates that dopamine may, under certain circumstances, play a role in the mediation of central nervous system tissue damage. Furthermore, recent studies suggest a synergistic role between the neurotoxic effects of excitatory amino acids and dopamine. To address this issue, rats received a unilateral injection of 6-hydroxydopamine or vehicle into the medial forebrain bundle. After recovery (18 days), both groups of animals received an ibotenic acid injection of the ipsilateral striatum. Seven days later the brains were removed and the size of the striatal lesion was assessed histologically and by means of receptor autoradiography. Regional analysis of profound D1 receptor loss was determined using [3H]SCH 23390, and extent of astrocytic proliferation was examined using autoradiography with the peripheral benzodiazepine receptor ligand [3H]R05-4864. Prior interruption of the nigrostriatal pathway (resulting in dopaminergic denervation of the ipsilateral striatum) partially protected this latter structure from subsequent injection of ibotenic acid (the extent of the lesion was reduced by 28%, P less than .05). The findings indicate that endogenous dopamine release may modulate (and intensify) the excitotoxic effects of ibotenic acid.

Animals↗
PubMed1991

Quinolinic acid lesion of nucleus accumbens reduces D1 but not D2 dopamine receptors: an autoradiographic study.

Information concerning the cellular localization of dopamine receptor subtypes in the nucleus accumbens (NAcc) was obtained using receptor autoradiographic analysis. Unilateral, stereotaxic injection of the axon-sparing neurotoxin, quinolinic acid, into the NAcc resulted in a prominent loss of dopamine D1 receptors (as labeled by [3H]SCH 23390). Contrarily, no appreciable decrement in D2 receptors (labeled by [3H]raclopride) could be identified within the same region of the NAcc. The findings support the view that accumbens D1 receptors are located postsynaptically on neurons or their processes, while D2 receptors within this nucleus are primarily located on afferent terminals.

Animals↗
PubMed1990

Nigral dopamine type-1 receptors are reduced in Huntington's disease: a postmortem autoradiographic study using [3H]SCH 23390 and correlation with [3H]forskolin binding.

Intrastriatal injection of excitatory amino acids, particularly quinolinic acid, has been proposed as an animal model of Huntington's disease. Such neurotoxic lesions of caudate-putamen result in marked dopamine type-1 (D1) receptor losses in the injected nuclei as well as in the ipsilateral substantia nigra pars reticulata. Postmortem human substantia nigra from Huntington's disease brains and from control brains were examined using in vitro autoradiography. A marked reduction in [3H]SCH 23390 binding (labeling D1 receptors) in the substantia nigra of postmortem brains of Huntington's patients was identified, thus paralleling the alterations seen in the animal models. A positive, statistically significant correlation was also encountered between D1 receptor binding (labeled by [3H]SCH 23390) and [3H]forskolin binding (which identifies adenylate cyclase, a second messenger system linked to D1 receptor activation). The results suggest that in the human--as in lower vertebrates--D1 receptors are located on striatonigral terminals and that D1 receptor loss tends to be paralleled by a reduction in adenylate cyclase. Radioactive agents selective for the D1 receptor may prove useful in future studies of Huntington's disease using positron emission tomography scanning.

Adolescent↗
PubMed1989

Localization of the dopamine uptake complex using [3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP) in rat brain.

[3H]N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP) is a novel phencyclidine derivative with considerable selectivity for dopamine uptake sites. [3H]BTCP was used to label dopamine uptake sites in vitro, in rat brain, and the regions containing these sites were visualized with an autoradiographic technique. The binding was found to be highest in the striatum, where greater than 90% of binding was specific. Furthermore, 6-hydroxydopamine lesions of the nigrostriatal pathway obliterated striatal [3H]BTCP binding ipsilaterally, whereas ibotenic acid injection into the caudate-putamen failed to significantly reduce [3H]BTCP binding in that structure. These results indicate that [3H]BTCP labels dopamine uptake sites in mammalian brain and that it can be employed for autoradiographic studies of this transport complex.

Animals↗
PubMed1989

[Treatment of morbid obesity by gastric bypass. Apropos of 1158 cases treated surgically].

After defining pathological obesity and describing the technical methods used for gastric bypass, a series of 1158 surgical cases is analysed. Discussion, supported by a review of the literature, involved post-operative mortality and morbidity, mid-term results and patient selection criteria. In the light of the results obtained, it would no longer appear justified to offer this type of surgical procedure.

Adolescent↗