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Biomedical subjects

M Levivier

Publications and source records attributed to M Levivier.

88 records · Page 5Linked to original sources

Striatal implants protect the host striatum against quinolinic acid toxicity.

Quinolinic acid (QA) and related excitotoxins produce a pattern of neuronal loss and neurochemical changes in the rat striatum similar to that of patients suffering from Huntington's disease, suggesting neurotoxicity is important in the etiology of that disease. Thus, strategies for limiting excitotoxin-induced striatal damage, like that caused by QA, may be of great benefit to these individuals. Accordingly, we tested the ability of both neural and non-neural tissue implants to protect the rat striatum against a subsequent QA challenge. Our results demonstrated that recipients of fetal striatal grafts were significantly less affected by striatal injections of QA than non-grafted animals. In contrast to the latter, fetal striatal tissue recipients did not exhibit apomorphine-induced rotation behavior and showed a sparing of cholinergic and enkephalinergic systems normally lost following QA injections. Animals grafted with adult rat sciatic nerve, adrenal medulla or adipose tissue all showed a less dramatic behavioral protection and sparing of cholinergic and enkephalinergic systems. These results suggest that fetal striatal tissue exerts an optimal, and perhaps specific protective influence on the host brain.

Adrenal Medulla↗

Sarcoidosis presenting as an isolated intramedullary tumor.

We report a case of isolated intramedullary sarcoidosis. The patient developed progressive signs that indicated a spinal tumor, which were investigated with contrast-enhanced magnetic resonance imaging scans. Magnetic resonance imaging clearly revealed an intramedullary lesion, but the diagnosis of sarcoidosis was made on the pathological analysis of the surgical specimen. Magnetic resonance imaging with contrast enhancement is reported in a histologically proven case of intramedullary sarcoidosis. Only 12 other cases of isolated intramedullary sarcoidosis have been reported. We review and discuss these cases according to their clinical presentation, the segmental location of the granulomas in the spinal cord, preoperative and operative diagnoses, and signs for systemic sarcoidosis. In none of the cases was the diagnosis of intramedullary sarcoidosis made before surgery. We think that surgical therapy for intramedullary lesions is the best way to diagnose rare instances of benign lesions like sarcoidosis and to treat them in an appropriate manner.

Contrast Media↗

Unilateral MPTP-induced parkinsonism in monkeys. A quantitative autoradiographic study of dopamine D1 and D2 receptors and re-uptake sites.

The cynomolgus monkeys received a unilateral intracarotid injection of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in order to induce a chronic model of hemi-parkinsonism. The procedure was well tolerated by the animals. Unilateral injection of MPTP caused rigidity and bradykinesia of the contralateral limbs, but the animals were able to eat and drink without levodopa therapy. During spontaneous motor activity, animals rotated toward the lesioned side whereas systemic apomorphine injection stimulated circling toward the normal non-lesioned side. Twelve weeks after MPTP injection, we found a marked reduction in striatal and nigral [3H]-mazindol binding on the MPTP-injected side which is indicative of a loss in both dopaminergic nerve terminals and cell bodies. The unilateral dopaminergic denervation was associated with an ipsilateral increase in striatal and a reduction in nigral [3H]-spiperone-labelled D2 dopamine receptors; these changes are consistent with the known localization of the D2 receptors on striatal dopaminergic nerve terminals and on nigral dopaminergic cell bodies. In contrast, no changes in [3H]-SCH 23390-labelled D1 dopamine receptors were observed at the level of either the striatum or the substantia nigra. This study describes a well tolerated procedure which induces a clinical and morphological hemi-parkinsonian syndrome. This animal model may be useful in the studies of new antiparkinsonian drugs, for testing the functional efficacy of brain tissue implants and in the understanding of the physiopathogenesis of levodopa-induced dyskinesias.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Lesions of the pineal and tentorial region. Occipito-parietal approach in three-quarter prone position with infrasagittal craniotomy].

Surgical treatment of pineal-tentorial region lesions remains a challenge. The difficulty in approaching the pineal region can be verified with the number of operative plans that have been proposed to reach this area: transcallosal, occipital transtentorial, infratentorial supracerebellar approaches and sitting, prone or Concorde positions. This emphasizes the surgeon's dissatisfaction with the surgical techniques described. Recently, a three-quarter prone position with the bone flap placed under the midline has been described (1, 3, 8). We have decided to test this approach that we have slightly modified and we report our results on 13 cases: 2 arachnoid cysts, 3 vascular malformations and 8 tumors (3 brainstem gliomas, 2 dysgerminomas, 1 quadrigeminal plate metastasis and 1 meningioma plus 1 metastasis of the falx). Keeping the table in a horizontal plane, risks of air embolus are eliminated. Using the natural effect of gravity, traction on the occipital lobe is no more necessary and hemianopsia no more occurs. We recommand the parieto-occipital route which is the shortest way to reach epiphysis and falco-tentorial notch. We confirm the results of american colleagues (1, 3, 8, 15) and we advise to use this approach which seems to us the best way to treat pineal-tentorial lesions.

Adult↗

[Brain grafts: ethical and scientific aspects].

Neural grafting will dramatically modify the treatment of major cerebral and medullary illnesses. This new approach has already been used in Parkinson's disease, perhaps too early according to our knowledge in that field. Ethical problems are numerous with brain grafting but one may hope in next future a better understanding of the mechanisms involved in these procedures and a solution to most of ethical objections to perform that treatment.

Adrenal Medulla↗

[Protective effect of intrastriatal grafts in an experimental model of Huntington's disease. Behavioral and morphological correlation].

The intrastriatal injection of the excitotoxin quinolinic acid (Q.A.) in rats produces neuroanatomical and neurochemical changes mimicking those appearing in the striatum in Huntington's disease (H.D.). Although its cause is unknown, it has been hypothesized that the neurodegenerative changes seen in H.D. may result from the action of an endogenous toxin. Therefore, the development of new strategies for limiting or preventing Q.A.-or other neurotoxic-induced degeneration may be of therapeutic interest for neurodegenerative disorders. Accordingly, we tested the ability of various tissue transplants to protect the rat striatum against a subsequent Q.A. insult. Using a "unilateral model", i.e. unilateral intrastriatal grafts followed by an ipsilateral intrastriatal injection of Q.A., we were able to quantify a behavioral protective effect of the grafts in recording the apomorphine-induced rotational behavior that normally appears after the striatal Q.A.-induced lesion. Our results show that one of the tested tissue, fetal striatum, protects the recipients against the lesioned-induced rotational behavior that appeared in non-grafted lesioned animals. The other grafted tissues (adrenal medulla, peripheral nerve, adipose tissue) seemed to provide a less dramatic protection than fetal striatum; however, this difference did not reach significance. Quantification of the striatal neuronal loss showed that the behavioral protection is significantly correlated with a better neuronal survival in the grafted animals. These results suggest that intracerebral grafts can protect the host brain against a toxin-induced damage, like the one resulting from Q.A. intrastriatal injection. Though fetal striatal grafts seem to exert an optimal protection, this protective effect may at least partially result from a host-mediated response to the transplantation procedure. The mechanism underlying this protective effect is unclear, but the present data suggest that it might be related to a transplantation-induced astroglial reaction resulting in an increased neuronotrophic activity that could protect against the toxic effect of Q.A. The results of this study also support the concept that the effect of transplantations could occur through processes other than a direct restoration of deficient transmitters or a reconstruction of damaged pathways. Further characterization of the factors implicated in the present paradigm might conceivably open avenues for possible therapeutic preventive interventions in neurodegenerative disorders.

Animals↗

A survey of 65 tumors within the spinal cord: surgical results and the importance of preoperative magnetic resonance imaging.

Between January 1984 and December 1990, 65 intramedullary spinal cord tumors were diagnosed and operated on. In this series, all patients underwent magnetic resonance imaging investigations and were operated on with the Cavitron ultrasonic surgical aspirator whenever necessary. Major surgical difficulties have been found in patients previously treated by radiotherapy with or without biopsy. We found magnetic resonance imaging to be a highly sensitive imaging procedure and the method of choice for visualizing tumors within the spinal cord. Nevertheless, accurate diagnosis may only be suggested by magnetic resonance imaging, rather than made definitively. Surgery is necessary in every case in order to obtain a definite diagnosis. Radical surgery can be performed when a plane exists between the tumor and the normal spinal cord: biopsy or debulking with the Cavitron ultrasonic surgical aspirator should be performed when the tumor is infiltrative. We have performed 33 so-called total resections, 22 partial resections, and 10 biopsies, among which 5 were performed on lipomas. Surgical results were assessed at 3 months after surgery, showing 35 improvements (53%), 24 stabilizations (37%), and 6 deteriorations (10%).

Adolescent↗

Neuropeptide Y, somatostatin, and cholecystokinin neurone preservation in anaplastic astrocytomas.

Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptide Y, somatostatin, and cholecystokinin immunoreactivity have been identified in all seven supratentorial anaplastic astrocytomas studied. These neurones have been shown not only on the edge but also in the depth of the neoplastic tissue. These neuropeptides were not present in 18 other intracranial tumours (3 astrocytomas, 1 subependymoma, 8 glioblastoma multiformes, 1 meningioma, and 5 metastases). In all 25 intracranial tumours studied, no immunoreactivity was found for vasoactive intestinal polypeptide, substance P, methionine-enkephalin, leucine-enkephalin, synenkephalin, neurophysin I-II, and corticotropin releasing factor.

Astrocytoma↗

Unusual pattern of somatosensory and brain-stem auditory evoked potentials after cardio-respiratory arrest.

Two patients in coma after cardio-pulmonary arrest showed bilateral absence of all brain-stem auditory evoked potentials contrasting with normal brain-stem reflexes and normal somatosensory cortical evoked potentials. In both patients pre-existing dysfunction of peripheral auditory structures could be ruled out. Subsequent neuropathological analysis showed that the anoxic-ischaemic lesions were restricted to Sommer's sector and the Purkinje cells. These unusual data suggest the hypothesis that a severe hypoxic-ischaemic insult may impair cochlear function and interfere with the activation of the intact auditory pathways.

Aged↗

Neurotensin high affinity binding sites and endopeptidase 24.11 are present respectively in the meningothelial and in the fibroblastic components of human meningiomas.

The presence of neurotensin receptors and endopeptidase 24.11 (E-24.11) in 16 human meningioma specimens, obtained at surgery, was assessed by measuring the binding of 125I-[tyrosyl3]neurotensin(1-13) (125I-NT) and the inhibitor 3H-N(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)glycine (3H-HACBO-Gly), for the receptor and enzyme, respectively. E-24.11 activity was also measured. Autoradiography, on the 16 meningiomas, showed that specific 125I-NT labeling (nonspecific labeling was assessed in the presence of excess NT) was exclusively located in the meningothelial regions. In contrast, specific 3H-HACBO-Gly labeling (nonspecific labeling was assessed in the presence of an excess of the E-24.11 inhibitor thiorphan) was exclusively found in fibroblastic regions. No specific labeling of either ligand was found on collagen or blood vessels. In vitro binding assays were performed on membranes of 10 of the 16 meningiomas. In the 4 meningiomas rich in meningothelial cells, 125I-NT specifically bound to one population of sites with Bmax ranging from 57 to 405 fmol/mg protein and Kd around 0.3 nM. These sites share common properties with the brain NT receptor, since the carboxy terminal acetyl NT(8-13) fragment bound to the same sites but with a higher affinity. The carboxy terminal analogue of NT, neuromedin N, also bound to the same sites with a 10-fold lower affinity and the sites were bradykinin and levocabastine insensitive. In the 4 meningiomas rich in fibroblastic cells, 3H-HACBO-Gly specifically bound to one population of sites with Bmax ranging from 251 to 739 fmol/mg protein and Kd around 2.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterization of nuclear size, ploidy, DNA histogram type and proliferation index in 79 nerve sheath tumors.

The distribution values of ploidy, of the DNA histogram type, of the proliferation index and of the nuclear area are described in a series of 79 nerve sheath tumors including 7 traumatic neuromas, 55 primary and 9 recurrent benign schwannomas, 5 benign neurofibromas and 3 malignant tumors. The nuclear parameters were computed on Feulgen-stained nuclei (from archival formalin-fixed paraffin-embedded materials) by means of digital cell image analysis. The results show that 20-30% of benign nerve sheath tumors exhibit an abnormal nuclear DNA content (DNA index > 1.30). Such a feature was observed in the four groups of benign tumors, i.e. primary and recurrent schwannomas, neurofibromas and even traumatic neuromas. Aneuploid tumors exhibited triploid, hypertriploid or polymorphic DNA histogram types. The three malignant tumors under study were aneuploid. Lastly, the nuclear area and proliferation index measurements did not allow any clear distinction to be made between the four groups of benign tumors on the one hand, and between the benign and malignant tumors on the other.

Adult↗

Epidermal growth factor receptors in human tumors of the central nervous system.

Epidermal growth factor receptors (EGF-R) have been measured in human tumors of the Central Nervous System (CNS) by 125I EGF ligand binding. High affinity receptors (Ka congruent to 1 x 10(9) M-1) were detected in nearly all individual specimens of meningiomas and tumors of glial origin (astrocytomas, glioblastomas). The phosphotyrosine kinase activity associated with the EGF-R was evaluated by measuring the incorporation of gamma 32P-ATP, after immunoprecipitation of the receptor with the monoclonal antibody EGFRI. A good relationship was observed between the EGF-binding capacity and the autophosphorylation of the receptor, indicating that in most cases functional molecules of EGF-R were expressed on the tumor membranes. In the group of meningiomas, no relationship could be established between the EGF-R level and the histopathology of the tumors. Astrocytomas exemplify a progression of malignancy, from benign (low grade astrocytomas) towards an increased malignant phenotype (glioblastomas). In this group, our observations indicate a positive relationship between the EGF-R level and phosphokinase activity and the degree of malignancy.

Brain Neoplasms↗