Papers by marc-etienne Corthesy
European Journal of Neuroscience, Aug 1, 1999
One hundred days after unilateral Crow nerve transection in the adult mouse whiskerpad, the cauda... more One hundred days after unilateral Crow nerve transection in the adult mouse whiskerpad, the caudal follicles of row C are reinnervated with » 80 % of the original number of axons [Corthe  sy, M.-E., Bronchti, G. & Welker, E. (1999) Eur. J. Neurosci., 11, 2835±2846]. To what extent is this reinnervation functional, and how does it interact with the enlargement of the functional representation of neighbouring rows subsequent to the denervation? Using the autoradiographic deoxyglucose method, we studied the whisker representation at the level of the barrel cortex 100 days post lesionem. We stimulated whiskers belonging to the denervated row C, the neighbouring rows B and D, or to all ®ve rows A±E. The deoxyglucose uptake was measured in tangential sections through layer IV. The results indicate that, 100 days post lesionem, whiskers of row C reactivate their cortical barrels. However, (i) the magnitude of this cortical response was reduced; (ii) row C barrels were equivalently activated by the stimulation of the neighbouring rows; and (iii) when all whiskers were stimulated, we observed a signi®cantly reduced deoxyglucose uptake over the representation of nonlesioned whiskers of rows D and E. Therefore, 100 days after the peripheral nerve lesion the reinnervation of the whiskerpad had not restored a normal pattern of activation at the level of the barrel cortex. We propose that this is due to a modi®ed interaction between the representations of the various rows of follicles at the cortical level that does not return to normal.
Journal of Neurosurgery, May 1, 1999
ARKINSON'S disease is produced by deregulated, dysfunctional neural activity in the medial globus... more ARKINSON'S disease is produced by deregulated, dysfunctional neural activity in the medial globus pallidus (GPm). 8,13,14,38 Clinical studies have empirically identified the GPm as an effective target for ablation to relieve the syndrome. 6,20,26 Despite advances in surgical technique and the use of electrophysiological monitoring to identify pallidal neurons, 19,25,35 techniques now in use for ablation using radiofrequency or radiation 12,17,33 are inherently not selective and jeopardize the internal capsule and the optic tract, which lie adjacent to the GPm. 18,20 Therefore, the extent and location of pallidal lesions that can be made safely with those techniques are limited. Selectively active neurotoxins such as excitotoxins 1 provide a chemical means of destroying pallidal neurons while preserving adjacent glial cells and axonal fibers of passage that may be damaged when using nonselective techniques. 9,15 However, these agents cannot be administered by traditional techniques for regional drug delivery in the human central nervous system, because those delivery techniques rely on diffusion of molecules from the point of administration. In contrast, it has recently been shown that high-flow microinfusion can be used to produce interstitial convection of fluid in the brain at relatively homogeneous concentrations 11,24,29 and to deliver drugs efficiently to large nuclei 24 or other brain regions. 23 Initially, to test the feasibility of using high-flow micro-infusion of an excitotoxin to lesion a large nucleus in the primate brain, we perfused the GPm in two naive rhesus macaques with either kainic acid or ibotenic acid. Subsequently, to test the therapeutic potential of this paradigm in six monkeys that previously had been rendered unilaterally parkinsonian by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 we compared the behavior and brain tissue characteristics in three animals infused with kainic acid with those in another three animals that received control infusions. Materials and Methods The housing, care, handling, procedures, and anesthesia used for the rhesus macaques in this study were in accordance with the Guidelines on the Use of Animals in Experimental Research from the National Institutes of Health and were approved by the National Institute of Neurologic Disorders and Stroke Animal Care and Use Committee. Direct Interstitial Infusion of the GPm Operative procedures were identical for the determination of feasibility and for examining the therapeutic potential of neurotoxin infusion. After anesthesia had been induced by intramuscular administration of ketamine (10 mg/kg) and xylazine (3 mg/kg) and intravenous administration of thiopental-sodium (2-6 mg/kg), each macaque underwent placement of a No. 4 French endotracheal tube.
European Journal of Neuroscience, Aug 1, 1999
One hundred days after unilateral Crow nerve transection in the adult mouse whiskerpad, the cauda... more One hundred days after unilateral Crow nerve transection in the adult mouse whiskerpad, the caudal follicles of row C are reinnervated with » 80 % of the original number of axons [Corthe  sy, M.-E., Bronchti, G. & Welker, E. (1999) Eur. J. Neurosci., 11, 2835±2846]. To what extent is this reinnervation functional, and how does it interact with the enlargement of the functional representation of neighbouring rows subsequent to the denervation? Using the autoradiographic deoxyglucose method, we studied the whisker representation at the level of the barrel cortex 100 days post lesionem. We stimulated whiskers belonging to the denervated row C, the neighbouring rows B and D, or to all ®ve rows A±E. The deoxyglucose uptake was measured in tangential sections through layer IV. The results indicate that, 100 days post lesionem, whiskers of row C reactivate their cortical barrels. However, (i) the magnitude of this cortical response was reduced; (ii) row C barrels were equivalently activated by the stimulation of the neighbouring rows; and (iii) when all whiskers were stimulated, we observed a signi®cantly reduced deoxyglucose uptake over the representation of nonlesioned whiskers of rows D and E. Therefore, 100 days after the peripheral nerve lesion the reinnervation of the whiskerpad had not restored a normal pattern of activation at the level of the barrel cortex. We propose that this is due to a modi®ed interaction between the representations of the various rows of follicles at the cortical level that does not return to normal.
Journal of Neurosurgery, 1999
Object. Selective treatment of central nervous system (CNS) structures holds therapeutic promise ... more Object. Selective treatment of central nervous system (CNS) structures holds therapeutic promise for many neurological disorders, including Parkinson's disease (PD). The ability to inhibit or augment specific neuronal populations within the CNS reliably by using present therapeutic techniques is limited. To overcome this problem, the authors modeled and developed a method in which convection was used to deliver compounds to deep brain nuclei in a reproducible, homogeneous, and targeted manner. To determine the feasibility and clinical efficacy of convective drug delivery for treatment of a neurological disorder, the investigators selectively ablated globus pallidus internus (GPi) neurons with quinolinic acid (QA), an excitotoxin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)—induced model of primate parkinsonism.Methods. After the parameters of convective distribution to the GPi were confirmed by infusion of biotinylated albumin into the GPi of a primate (Macaca mul...
European Journal of Cardio-Thoracic Surgery, 1998
Objectives: Pulmonary sequestration is a continuum of lung anomalies for which no single embryoni... more Objectives: Pulmonary sequestration is a continuum of lung anomalies for which no single embryonic hypothesis is yet available. The aim of this study was to assess the diagnostic tools and treatment for the rare condition, pulmonary sequestration, in an unspecialised centre. Methods: We performed an analysis of 26 cases of pulmonary sequestration (paediatric and adult) operated at the Centre Hospitalier Universitaire Vaudois between May 1959 and May 1997. A review of the extralobar and intralobar types of sequestrations is discussed. Angiography is compared to other diagnostic tools in this condition, and treatment is discussed. Results: Twenty-six cases of pulmonary sequestrations, a rare congenital pulmonary malformation, were operated on in the defined time period. Seventy-three percent (19) of the cases were intralobar and 27% (seven) extralobar. Extralobar localisation was basal in 71% and situated between the upper and the lower lobe in 29%. In six cases, the diagnosis was made by exploratory thoracotomy. In the other 20 cases, diagnosis was evoked on chest X-ray and confirmed by angiography. Lobectomy (46%) was the most common treatment procedure. Segmental resection was performed in 30% of the cases and bilobectomy in 4%. Post-operative morbidity was low. The most significant complications were pleural empyema, haemothorax and haemopneumoperitoneum in case of extralobar sequestration. There was no evidence of metaplasia or pre-neoplastic changes. Conclusions: Despite its rarity, some radiological features are sufficiently suggestive of diagnosis of pulmonary sequestration. Investigations are necessary in order to avoid unexpected pathology at the time of operation. Resection of the involved lung leads to excellent results and the long-term outcome is highly favourable.
European Journal of Neuroscience, 1999
One hundred days after unilateral Crow nerve transection in the adult mouse whiskerpad, the cauda... more One hundred days after unilateral Crow nerve transection in the adult mouse whiskerpad, the caudal follicles of row C are reinnervated with » 80 % of the original number of axons [Corthe  sy, M.-E., Bronchti, G. & Welker, E. (1999) Eur. J. Neurosci., 11, 2835±2846]. To what extent is this reinnervation functional, and how does it interact with the enlargement of the functional representation of neighbouring rows subsequent to the denervation? Using the autoradiographic deoxyglucose method, we studied the whisker representation at the level of the barrel cortex 100 days post lesionem. We stimulated whiskers belonging to the denervated row C, the neighbouring rows B and D, or to all ®ve rows A±E. The deoxyglucose uptake was measured in tangential sections through layer IV. The results indicate that, 100 days post lesionem, whiskers of row C reactivate their cortical barrels. However, (i) the magnitude of this cortical response was reduced; (ii) row C barrels were equivalently activated by the stimulation of the neighbouring rows; and (iii) when all whiskers were stimulated, we observed a signi®cantly reduced deoxyglucose uptake over the representation of nonlesioned whiskers of rows D and E. Therefore, 100 days after the peripheral nerve lesion the reinnervation of the whiskerpad had not restored a normal pattern of activation at the level of the barrel cortex. We propose that this is due to a modi®ed interaction between the representations of the various rows of follicles at the cortical level that does not return to normal.
Journal of …, 1999
ARKINSON'S disease is produced by deregulated, dysfunctional neural activity in the medial globus... more ARKINSON'S disease is produced by deregulated, dysfunctional neural activity in the medial globus pallidus (GPm). 8,13,14,38 Clinical studies have empirically identified the GPm as an effective target for ablation to relieve the syndrome. 6,20,26 Despite advances in surgical technique and the use of electrophysiological monitoring to identify pallidal neurons, 19,25,35 techniques now in use for ablation using radiofrequency or radiation 12,17,33 are inherently not selective and jeopardize the internal capsule and the optic tract, which lie adjacent to the GPm. 18,20 Therefore, the extent and location of pallidal lesions that can be made safely with those techniques are limited. Selectively active neurotoxins such as excitotoxins 1 provide a chemical means of destroying pallidal neurons while preserving adjacent glial cells and axonal fibers of passage that may be damaged when using nonselective techniques. 9,15 However, these agents cannot be administered by traditional techniques for regional drug delivery in the human central nervous system, because those delivery techniques rely on diffusion of molecules from the point of administration. In contrast, it has recently been shown that high-flow microinfusion can be used to produce interstitial convection of fluid in the brain at relatively homogeneous concentrations 11,24,29 and to deliver drugs efficiently to large nuclei 24 or other brain regions. 23 Initially, to test the feasibility of using high-flow micro-infusion of an excitotoxin to lesion a large nucleus in the primate brain, we perfused the GPm in two naive rhesus macaques with either kainic acid or ibotenic acid. Subsequently, to test the therapeutic potential of this paradigm in six monkeys that previously had been rendered unilaterally parkinsonian by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 we compared the behavior and brain tissue characteristics in three animals infused with kainic acid with those in another three animals that received control infusions. Materials and Methods The housing, care, handling, procedures, and anesthesia used for the rhesus macaques in this study were in accordance with the Guidelines on the Use of Animals in Experimental Research from the National Institutes of Health and were approved by the National Institute of Neurologic Disorders and Stroke Animal Care and Use Committee. Direct Interstitial Infusion of the GPm Operative procedures were identical for the determination of feasibility and for examining the therapeutic potential of neurotoxin infusion. After anesthesia had been induced by intramuscular administration of ketamine (10 mg/kg) and xylazine (3 mg/kg) and intravenous administration of thiopental-sodium (2-6 mg/kg), each macaque underwent placement of a No. 4 French endotracheal tube.
Journal of …, 1999
ARKINSON'S disease is produced by deregulated, dysfunctional neural activity in the medial globus... more ARKINSON'S disease is produced by deregulated, dysfunctional neural activity in the medial globus pallidus (GPm). 8,13,14,38 Clinical studies have empirically identified the GPm as an effective target for ablation to relieve the syndrome. 6,20,26 Despite advances in surgical technique and the use of electrophysiological monitoring to identify pallidal neurons, 19,25,35 techniques now in use for ablation using radiofrequency or radiation 12,17,33 are inherently not selective and jeopardize the internal capsule and the optic tract, which lie adjacent to the GPm. 18,20 Therefore, the extent and location of pallidal lesions that can be made safely with those techniques are limited. Selectively active neurotoxins such as excitotoxins 1 provide a chemical means of destroying pallidal neurons while preserving adjacent glial cells and axonal fibers of passage that may be damaged when using nonselective techniques. 9,15 However, these agents cannot be administered by traditional techniques for regional drug delivery in the human central nervous system, because those delivery techniques rely on diffusion of molecules from the point of administration. In contrast, it has recently been shown that high-flow microinfusion can be used to produce interstitial convection of fluid in the brain at relatively homogeneous concentrations 11,24,29 and to deliver drugs efficiently to large nuclei 24 or other brain regions. 23 Initially, to test the feasibility of using high-flow micro-infusion of an excitotoxin to lesion a large nucleus in the primate brain, we perfused the GPm in two naive rhesus macaques with either kainic acid or ibotenic acid. Subsequently, to test the therapeutic potential of this paradigm in six monkeys that previously had been rendered unilaterally parkinsonian by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 we compared the behavior and brain tissue characteristics in three animals infused with kainic acid with those in another three animals that received control infusions. Materials and Methods The housing, care, handling, procedures, and anesthesia used for the rhesus macaques in this study were in accordance with the Guidelines on the Use of Animals in Experimental Research from the National Institutes of Health and were approved by the National Institute of Neurologic Disorders and Stroke Animal Care and Use Committee. Direct Interstitial Infusion of the GPm Operative procedures were identical for the determination of feasibility and for examining the therapeutic potential of neurotoxin infusion. After anesthesia had been induced by intramuscular administration of ketamine (10 mg/kg) and xylazine (3 mg/kg) and intravenous administration of thiopental-sodium (2-6 mg/kg), each macaque underwent placement of a No. 4 French endotracheal tube.
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Papers by marc-etienne Corthesy