53 results on '"Lindvall O"'
Search Results
2. Septal cholinergic neurons suppress seizure development in hippocampal kindling in rats: comparison with noradrenergic neurons
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Ferencz, I., Leanza, G., Nanobashvili, A., Kokaia, Z., Kokaia, M., and Lindvall, O.
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- 2001
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3. Stereological assessment of vulnerability of immunocytochemically identified striatal and hippocampal neurons after global cerebral ischemia in rats
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Larsson, E., Lindvall, O., and Kokaia, Z.
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- 2001
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4. Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain
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Arvidsson, A., Kokaia, Z., Airaksinen, M. S., Saarma, M., and Lindvall, O.
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- 2001
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5. Increased synaptic inhibition in dentate gyrus of mice with reduced levels of endogenous brain-derived neurotrophic factor
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Olofsdotter, K., Lindvall, O., and Asztely, F.
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- 2000
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6. Increased neurogenesis in a model of electroconvulsive therapy
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Madsen, T. M., Treschow, A., Bengzon, J., Bolwig, T. G., Lindvall, O., and Tingstrom, A.
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- 2000
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7. Differential regulation of mRNAs for neuropeptide Y and its receptor subtypes in widespread areas of the rat limbic system during kindling epileptogenesis
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Kopp, J., Nanobashvili, A., Kokaia, Z., Lindvall, O., and Hokfelt, T.
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- 1999
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8. Regulation of norepinephrine transporter and tyrosine hydroxylase mRNAs after kainic acid-induced seizures
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Bengzon, J., Hansson, S.R., Hoffman, B.J., and Lindvall, O.
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- 1999
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9. Hyperglycemia and Hypercapnia Suppress BDNF Gene Expression in Vulnerable Regions after Transient Forebrain Ischemia in the Rat
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Uchino, H., Lindvall, O., Siesjö, B. K., and Kokaia, Z.
- Abstract
Preischemic hyperglycemia or superimposed hypercapnia exaggerates brain damage caused by transient forebrain ischemia. Because high regional levels of brain-derived neurotrophic factor (BDNF) protein correlate with resistance to ischemic damage, we studied the expression of BDNF mRNA using in situhybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, hyperglycemic, or hypercapnic conditions. Compared with normoglycemic animals, the increase of BDNF mRNA in dentate granule cells was attenuated and that in CA3 pyramidal neurons completely prevented in hyperglycemic rats. No ischemia-induced increases of BDNF mRNA levels in the hippocampal formation were detected in hypercapnic animals. Hyperglycemic and hypercapnic rats showed transiently decreased expression of BDNF mRNA levels in the cingulate cortex, which was not observed in normoglycemic animals. The results suggest that suppression of the BDNF gene might contribute to the increased vulnerability of the CA3 region and cingulate cortex in hyperglycemic and hypercapnic animals.
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- 1997
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10. Neuronal damage in the striatum following forebrain ischemia: lack of effect of selective lesions of mesostriatal dopamine neurons
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Wieloch, T., Miyauchi, Y., and Lindvall, O.
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Transient periods of global cerebral ischemia lead to selective neuronal damage in the striatum. We investigated the effects of unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine (DA) system on the density and distribution of neuronal necrosis in the rat striatum following ischemia induced by bilateral occlusion of the common carotid arteries combined with hypotension. After both 12 and 15 min of ischemia, which caused slight and extensive striatal damage, respectively, there was no difference in the density of neuronal necrosis in the striatum between DA-lesioned and shamoperated animals. We conclude that the DA system alone does not modulate injury following complete cerebral ischemia, but may contribute significantly to damage following conditions such as during hypoglycemia and incomplete cerebral ischemia.
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- 1990
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11. Electrical stimulation of the lateral habenula increases hippocampal noradrenaline release as monitored by in vivo microdialysis
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Kalén, P., Lindvall, O., and Björklund, A.
- Abstract
Hippocampal extracellular levels of noradrenaline (NA) were monitored with the microdialysis technique during electrical stimulation of the lateral habenula (LHb) in halothane anaesthetized rats. The steady state NA level was 20.8±4.6 fmole/15 min of perfusion (mean ± SEM). Electrical stimulation of the LHb for 15 min (15 Hz, 0.5 mA) induced an immediate 228±48% increase in hippocampal NA release, compared to the pre-stimulation baseline (p<0.05). A second stimulation 90 min later induced a similar increase. The effect of LHb stimulation was completely abolished by a knife cut transecting the dorsal NA bundle either immediately rostral to the locus coeruleus or at the level of the parafascicular nucleus. This suggests that the effect was dependent on nerve impulses flow in the coeruleo-hippocampal NA neurons, and was not mediated, e.g., by a local spread of electricity into the hippocampus. Since the LHb has previously been shown to be a powerful activator of the mesencephalic raphe nuclei we tested whether the effect was mediated via the serotonergic system. However, the effect of LHb stimulation on hippocampal NA release persisted after 5,7-di-hydroxytryptamine treatment and after complete radiofrequency lesions of the dorsal and central superior raphe nuclei. The present data suggest that electrical stimulation of the LHb can increase hippocampal NA release through an activation of the locus coeruleus, and that this effect is not dependent on the mesencephalic raphe nuclei. The results support the role of the LHb as a link for limbic and striatal forebrain activation of brain stem monoaminergic systems.
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- 1989
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12. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release
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Brundin, P., Strecker, R., Widner, H., Clarke, D., Nilsson, O., Åstedt, B., Lindvall, O., and Björklund, A.
- Abstract
Summary: We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5–8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosup-pressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.
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- 1988
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13. Functional reactivation of the deafferented hippocampus by embryonic septal grafts as assessed by measurements of local glucose utilization
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Kelly, P., Gage, F., Ingvar, M., Lindvall, O., Stenevi, U., and Björklund, A.
- Abstract
Summary: Transection of the septo-hippocampal connections through fimbria-fornix damage in the rat results in profound hippocampal cholinergic deafferentation, and, when applied bilaterally, leads to severe and long-lasting impairments in learning and memory. Previous studies have shown that intrahippocampal septal grafts can reestablish a new cholinergic innervation in the inititally denervated hippocampal formation and at least partly compensate for the lesion-induced learning impairments in fimbria-fornix lesioned rats. The purpose of the present study was to determine the magnitude of lesion-induced alterations in cerebral function as reflected in local glucose use measured by (
14 C)-2-deoxyglucose (2-DG) autoradiography, and the degree to which this index of functional activity could be normalized following reinnervation from transplants of fetal cerebral tissue from the primordial septal region. Six months after unilateral fimbriafornix transection the rate of glucose utilization was reduced markedly throughout the ipsilateral hippocampus when compared to the intact contralateral side, while in the neocortex only the cingulate cortex showed long-lasting reductions in glucose use. Rats that received a transplant of fetal septal-diagonal band tissue at the time of fimbria-fornix transection, and were sacrificed 6 months later, displayed significantly greater glucose utilization in the ipsilateral hippocampus and cingulate cortex than was measured in these areas in rats with lesion alone. The recovery in glucose use was paralleled by a significant increase in acetylcholinesterase (AChE) staining in several areas of the ipsilateral hippocampal formation and cingulate cortex. This index of graft-induced cholinergic reinnervation was, moreover, significantly correlated with the rate of glucose use. Thus, in the fimbria-fornix transected animals the magnitude of glucose depression correlated with the extent of reduction in AChE staining, and in the grafted animals the degree of normalization of glucose use was correlated with the graft-induced increase in AChE-staining density. These results thus indicate that the 2-DG autoradiographic technique can provide a unique opportunity to map both altered functional activity in localized areas of the brain following specific lesions and the extent to which transplant-derived reinnervation of the host may induce a return to normal functional levels in the target site.- Published
- 1985
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14. Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease
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Brundin, P., Nilsson, O. G., Strecker, R. E., Lindvall, O., Åstedt, B., and Björklund, A.
- Abstract
The ventral mesencephalon, containing the developing dopaminergic neurons of the substantia nigra-ventral tegmental region, was obtained from aborted human fetuses of 9–19 weeks of gestation. The tissue was grafted into the striatum of rats previously subjected to a 6-hydroxydopamine lesion of the mesostriatal dopamine pathway. The graft recipients were immunosuppressed by daily injections of Cyclosporin A. Amphetamine-induced motor asymmetry was reduced, and finally totally reversed, only in rats receiving grafts from the 9-week old fetal donor. The fluorescence microscopic analysis revealed large numbers of surviving dopamine neurons, and extensive fiber outgrowth into the host striatum, in these rats. By contrast, rats receiving grafts from 11–19 week old donors had at most only few surviving dopamine neurons. These results indicate that human fetal mesencephalic tissue may be an efficient source of dopamine neurons for functional intracerebral grafting in patients with Parkinson's disease.
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- 1986
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15. Short term status epilepticus in rats causes specific behavioral impairments related to substantia nigra necrosis
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Lindvall, O., Ingvar, M., and Gage, F. H.
- Abstract
Status epilepticus (SE) was induced for 40 min by flurothyl in well oxygenated rats. This insult resulted in selective destruction of up to 65% of the substantia nigra pars reticulata. We investigated the short and long term behavioral effects of this damage. No deficits were observed in sensorimotor reactivity, locomotor coordination, spontaneous or apomorphine-stimulated locomotor activity in the rats with induced epilepsy. However, these rats exhibited a long-lasting enhancement of amphetamine-stimulated locomotor activity. We propose that this selective impairment is caused by the necrosis of the pars reticulata. This damage might lead to deficient regulation either of mesostriatal dopamine neurons innervating nc. accumbens, or of neurons in the mesencephalic reticular formation mediating the locomotor response initiated in the nc. accumbens.
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- 1986
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16. Effects of Hibernation or Cryopreservation on the Survival and Integration of Striatal Grafts Placed in the Ibotenate-Lesioned Rat Caudate-Putamen
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Frodl, E. M., Sauer, H., Lindvall, O., and Brundin, P.
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- 1995
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17. Protective effect of platelet-derived growth factor against 6-hydroxydopamine-induced lesion of rat dopaminergic neurons in culture
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Pietz, K., Odin, P., Funa, K., and Lindvall, O.
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- 1996
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18. New aspects on factors determining the sensitivity of the formaldehyde and glyoxylic acid fluorescence histochemical methods for monoamines
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Lindvall, O., Björklund, A., Falck, B., and Lorén, I.
- Abstract
The fluorophore and fluorescence yield from tryptamine and 3-methoxytyramine in histochemical protein models have been compared in the standard formaldehyde reaction, the acid-catalyzed formaldehyde reaction, the formaldehyde-ozone reaction, and the aluminum-formaldehyde reaction. In the standard formaldehyde reaction both the fluorophore and fluorescence yields are low. However, the other reactions give a dramatic increase in fluorescence intensity (18–20 times) from tryptamine and 3-methoxytyramine whereas only minor changes (up to 100% increase) in fluorophore yield are observed. It is concluded that the relative fluorescence intensity of each fluorophore molecule formed in the three modifications of the formaldehyde reaction is much higher than that of the molecules formed in the standard formaldehyde reaction. It has previously been demonstrated that the fluorophores formed from dopamine in the gaseous formaldehyde and glyoxylic acid reactions have a much higher (10 times) relative fluorescence intensity than the synthetic fluorophores. The present experiments show that if the histochemical models are dissolved in buffer after the reaction and new models are made from this solution, the fluorescence intensity of the fluorophores formed in the reaction is drastically reduced and becomes comparable to that of the synthetic ones. The results of this and our previous studies indicate that hitherto unknown fluorescence enhancing mechanisms play a major role for the fluorescence yield, i.e. the sensitivity, in the various formaldehyde and glyoxylic acid methods. One possible explanation to the high relative fluorescence intensity of the fluorophores formed in the histochemical reactions could be an energy transfer between, e.g. the non-fluorescent intermediary reaction products (the tetrahydro derivatives) and the fluorophores (the dihydroisoquinolines and dihydro-ß-carbolines). Such an energy transfer is probably attenuated in the dissolved models, where the distances between and orientations of the various molecules have been changed.
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- 1980
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19. Application of the aluminum-formaldehyde (ALFA) histofluorescence method for demonstration of peripheral stores of catecholamines and indolamines in freeze-dried paraffin-embedded tissue, cryostat sections and whole-mounts
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Ajelis, V., Björklund, A., Falck, B., Lindvall, O., Lorén, I., and Walles, B.
- Abstract
This paper describes new procedures for highly sensitive visualization of monoamine stores in peripheral tissues, taking advantage of the recently introduced aluminum-catalysed formaldehyde (ALFA) reaction. The tissues are exposed to an aluminum sulphate solution (with or without formaldehyde fixation) in a perfusion and/or immersion step, followed by formaldehyde vapour treatment. Procedures are described for freeze-dried, paraffin embedded tissue, cryostat sections and whole mount preparations. For all these tissue preparations the ALFA method gives a highly sensitive and precise demonstration of catecholamine-containing neurons and 5-HT-containing cells in a variety of peripheral tissues. For freeze-dried tissue and cryostat sections the ALFA method represents an improvement in comparison with other available methods. This is particularly noticeable for the very delicate adrenergic nerves in such organs as the thyroid, ovary, pancreas and the gastrointestinal tract.
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- 1979
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20. New fluorophore-forming reactions for histochemical visualization of N-acetylated and tertiary indolamines using glyoxylic acid, aluminum-formaldehyde and trifluoroacetic acid anhydride as reagents
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Lindvall, O., Björklund, A., Falck, B., Lorén, I., and Svensson, L.-Å.
- Abstract
N-acetylated and tertiary indolamines, some of which are possible neurotransmitter candidates in the CNS, cannot be visualized with the standard Falck-Hillarp histofluorescence method and very little is known about their cellular localization. The present investigation demonstrates that glyoxylic acid (GA), formaldehyde (FA) in combination with aluminum ions (the ALFA method) and trifluoroacetic acid anhydride (TFAA) are capable of forming fluorescent compounds from N-acetylated (e.g. melatonin and N-acetyl-5-hydroxytryptamine) and tertiary (e.g. bufotenin) indolamines in histochemical protein models. With GA and FA-aluminum more vigorous reaction conditions were required for demonstration of these compounds compared to those needed for optimal visualization of primary catecholand indolamines (prolonged reaction time and higher concentration of GA and FA and aluminum ions). The fluorophore formation from N-acetylated and tertiary indolamines, which represents a new reaction principle in amine fluorescence histochemistry, is proposed to proceed as follows. In the first step, the indole reacts in 2-position with the reagent. The intermediate formed is dehydrated in the second step, yielding a strongly fluorescent 2-methylene derivative, which either per se or as the corresponding autoxidized dimer constitutes the main fluorophore. TFAA and related anhydrides represent new and potent reagents for histochemical visualization of N-acetylated indolamines such as melatonin. In contrast to the GA and ALFA reactions the optimal formation of fluorphores with TFAA required only mild reaction conditions (2–10 min at 0–20° C). The main fluorophore formed from melatonin has been identified and the reaction with TFAA is proposed to proceed as follows. An unstable intermediate, the isoimidinium carboxylate, is formed in the first step and this compound is then cyclized to form the fluorophore, 6-methoxy-1-methyl-3,4-dihydro-ß-carboline. The GA and ALFA methods are already widely used for visualization of catecholamine systems. The fluorescence microscopical and microspectrofluorometric analysis did not, however, veveal any specific structures containing N-acetylated or tertiary indolamines in the rat CNS. The TFAA reaction was highly specific for N-acetylated indolamines when applied to protein models. However, in tissue a disturbing background fluorescence appeared, which under all reaction conditions tested, developed concomitantly with the specific fluorescence from melatonin. The problem with this background reaction has to be solved before the TFAA reaction can be applied for demonstration of N-acetylated indolamines in tissue.
- Published
- 1981
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21. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain
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Harms, L., Bock, A., JÄnisch, W., Valdueza, J., Weber, J., Link, I., De Keyser, J., Goossens, A., Wilczak, N., Vedeler, C., Bjorge, L., Uvestad, E., Conti, G., Williams, K., Ginsberg, L., Rafique, S., Rapoport, S. I., Gershfeld, N. L., De La Meilleure, G., Crevits, L., Faiss, J. H., Heye, N., Blanke, J., Sackmann, A., Kastrup, O., Doornbos, R., van der Worp, H. B., Kappelle, L. J., Bar, P. R., Davie, C. A., Barker, G. J., Brenton, D., Miller, D. H., Thompson, A. J., Block, F., Schwarz, M., Delodovici, L., Baruzzi, F., Bonaldi, G., Dario, A., Marra, A., Mercuri, A., Dworzak, F., Cavallari, P., Confalonieri, P., Zuffi, M., Antozzi, C., Cornelio, F., Baldissera, F., Chassande, B., Ameri, A., Eymard, B., Poisson, M., Vérier, A., Brunet, P., Congia, S., Murgia, P. L., Cannas, A., Borghero, G., Uselli, S., Mellino, G., Ferrai, R., Lampis, R., Massa, R., Muzzetto, B., Giannini, F., Rossi, S., Cioni, R., d'Aniello, C., Guarneri, A., Battistini, N., Ceriani, F., Del Santo, A., Poloni, M., Campo, J. F., Iglesias, F., Guitera, M. V., Farinas, C., Pascual, J., Leno, C., Berciano, J., Thorpe, I. W., Kendall, B. E., McDonald, W. I., Moulignier, A., Dromer, F., Baudrimont, M., Dupont, B., Gozlan, J., El Amrani, M., Petit, J. C., Roullet, E., Sterzi, R., Causaran, R., Protti, A., Riva, M., Erminio, F., Arena, O., Villa, F., Maccagnano, E., Miletta, M., Spinelli, F., Ben-Hur, T., Weidenfeldl, J., Rao, N. S., Chari, C. C., Laforet, P., Matheron, S., Adams, D., Chemouilli, Ph., Desi, M., Said, G., Davous, P., Lionnet, F., Pulik, M., Genet, P., Rozenberg, F., Cartier, L. M., Castillo, J. L., Cea, J. G., Villagra, R., de Saint Martin, L., Mahieux, F., Manifacier, M. J., Mattos, K., Queiros, C., Publio, L., Vinhas, V., PeÇanha-Martins, A. C., Melo, A., Liska, U., Zifko, U., Budka, H., Drlicek, M., Grisold, W., Kaufmann, R., Kaiser, R., Czygan, M., Gomes, I., Jones, N., Cunha, S., EmbiruÇu, E. Katiane, Vieira, V., Araujo, I., Alexandra, M., Ferreira, A., Goes, J., Chemouilli, P., Israel-Biet, Masson, H., Lacroix, C., Gasnault, J., Hildebrandt-Müller, B., Oschmann, P., Krack, P., Willems, W. R., Dorndorf, W., Freitas, V., Bittencourt, A., Fernandes, D., Nascimento, M. H., Severo, M., Moraes, D., Muller, M., Hasert, K., Merkelbach, S., Schimrigk, K., van Oosten, B. W., Lai, M., Polman, C. H., Bertelsmann, F. W., Hodgkinson, S., Cabre, P. H., Volpe, L., Smadja, D., Vernant, J. P., Villaroya, H., Violleau, K., Younes-Chennoufi, A. Ben, Baumann, N., Villanueva-Hemandez, P., Ballabriga, J., Basart, E., Arbizu, T. X., Perez-Serra, J., Vinuels, F., Giron, J. M., Castilla, J. M., Redondo, L., Izquierdo, G., Lauer, K., Henneberg, A., Bittmann, N., Link, D., Wollinsky, K. H., Mobner, R., Fassbender, K., Kuhnen, J., Schwartz, A., Hennerici, M., Miller, A., Lider, O., Abramsky, O., Weiner, H. L., Offner, H., Vanderbark, A. A., Paoino, E., Fainardi, E., Addonizio, M. C., Ruppi, P., Tola, M. R., Granieri, E., Carreras, M., Sazdovitch, V., Joutel, A., Verdier-taillefer, M. H., Heinzlef, O., Radder, C., Tournier-Lasserve, E., Brenner, R. E., Munro, P. M. G., Williams, S. C. R., Bell, J. D., Hawkins, C. P., Filippi, M., Campi, A., Dousset, V., Canal, N., Comi, G., Zhu, J., Weber, F., Retska, R., List, J., Zhang, L., Brock, M., Taphoorn, M. J. B., Heimans, J. J., van der Veen, E. A., Karim, A. B. M. F., Sarazin, M., Argentino, N., Delattre, J. Y., Derkinderen, P., Buchwald, B., Schroter, G., Serve, G., Franke, C. H., Conrad, B., Kitchen, N. D., Thomas, D. G. T., Forman, A. D., Ang, Kie- Kian, Price, R., Stephens, C., Salmaggi, A., Nermni, R., Silvani, A., Forno, M. G., Luksch, R., Boiardi, A., Grzelec, H., Fryze, C., Nowacki, P., Zdziarska, B., Sanson, M., Merel, P., Richard, S., Rouleau, G., Thomas, G., Olsen, N. K., Pfeiffer, P., Egund, N., Bentzen, S. M., Johannesen, L., Mondrup, K., Rose, C., Zyluk, B., Wondrusch, E., Berger, O., Fast, N., Jellinger, K., Lindner, K., Urman, A., Thibault, J. L., Duyckaerts, Ch., Strik, H., Muller, B., Richter, E., Krauseneck, P., Steinbrecher, A., Schabet, M., Hess, C., Bamberg, M., Dichgans, J., Counsell, C. E., McLeod, M., Grant, R., Creel, G. B., Claus, D., Sieber, E., Engelhardt, A., Rechlin, T., Thierauf, P., Neubauer, U., Peresson, M., Di Giovacchino, G., Romani, G. L., Di Silverio, F., Danek, A., Kuffner, M., Hoermann, R., Schopohl, J., Laska, M., Heye, B., Zangaladze, A. T., Valls-SoIè, J., Cammarota, A., Alvarez, R., Tolosa, E., Hallett, M., Ulbricht, D., Ganslandt, O., Kober, H., Vieth, J., Grummich, P., Pongratz, H., Brigel, C., Fahlbusch, R., Serra, F. P., Palma, V., Nolfe, G., Buscaino, G. A., Rothstein, T. L., Gibson, J. M., Morrison, P. M., Collins, A. D., Eiselt, M., Wagnur, H., Zwiener, U., Schindler, T., Efendi, H., Ertekin, C., Erfas, M., Larsson, L. E., Sirin, H., AraÇ, N., Toygar, A., Demir, Y., Seddigh, S., Vogt, T. H., Hundemer, H., Visbeck, A., Pastena, L., Faralli, F., Mainardi, G., Gagliardi, R., Linden, D., Berlit, P., Lopez, O. L., Becker, J. T., Jungreis, C., Brenner, R., Rezek, D., Dekesky, S. T., Estol, C., Boller, F., Fernandez, J. M., Mederer, S., Batlle, J., Turon, A., Codina, A., Hitzenberger, P., Vila, N., Valls-SolÇ, J., Chamorro, A., Pouget, J., Schmied, A., Morin, D., Azulay, J. Ph., Vedel, J. P., Montalt, J., Escudero, J., Barona, R., Campos, A., Varli, K., Ertem, E., Uludag, B., Yagiz, A., Privorkin, Z., Steinvil, Y., Kott, E., Combarros, O., Sanchez-Pernaute, R., Orizaola, P., Mokrusch, Th., Kutluaye, E., Selcuki, D., Ertikin, C., Zettl, U., Gold, R., Harvey, G. K., Hartung, H. P., Toyka, K. V., Wokke, J. H. J., Oey, P. L., Ippel, P. F., Jansen, G. H., Franssen, H., Toyooka, K., Fujimura, H., Ueno, S., Yoshikawa, H., Yorifuji, S., Yanagihara, T., Talamon, C., Tzourio, C., Kiefer, R., Jung, S., Toyka, K., Ruolt, I., Tranchant, C., Mohr, M., Warter, J. M., Younger, D. S., Rosoklija, G., Hays, A. P., Kurita, R., Hasegawa, O., Matsumto, M., Komiyama, A., Nara, Y., Oueslati, S., Belal, S., Turki, I., Ben Hamida, C., Hentati, F., Ben Hamida, M., Kwiecinski, H., Krolicki, L., Domzal-Stryga, A., Dellemijn, P. L. I., van Deventer, P., van Moll, B., Drogendijk, T., Vecht, Ch. J., Nemni, S., Amadio, Fazio, R., Galardin, G., Delodovici, M. L., Peghi, E., Monticelli, M. L., Sessa, A., Viguera, M. L., Palomar, M., Gamez, J., Cervera, C., Navarro, C., Serena, J., Duran, I., Fernandez, A. L., Comabella, M., Nos, C., Rio, J., Montalban, J., Navarro, X., Verdu, E., Darbra, S., Buti, M., Mrabet, A., Fredj, M., Gouider, R., Tounsi, H., Khalfallah, N., Haddad, A., Dbaiss, T., Ghnassia, R., Rouillet, E., Chedru, F., Porsche, H., Strenge, H., Li, S. W., Young, Y. P., Garcia, A. A., Baron, P., Scarpini, E., Bianchi, R., Conti, A., Livraghi, S., Rees, J. H., Gregson, N. A., Hughes, R. A. C., Sedano, M. J., Calleja, J., Canga, E., Bahou, Y., Biary, N., Al Deeb, S. M., Guern, E. L. E., Gugenheim, M., Tardieu, S., Aisonobe, T. M., Agid, Y., Bouche, P., Brice, A., Rautenstrauss, B., Nelis, E., Grehl, H., Van Broeckhoven, C., Pfeiffer, R. A., Liehr, T., Ganzmann, E., Gehring, C., Neundörfer, B., Geremia, L., Doronzo, R., Sacilotto, G., Sergi, P., Pastorino, G. C., Scarlato, G., Planté-Bordeneuve, V., Mantel, A., Baas, F., Moser, H., Antonini, A., Psylla, M., Günther, I., Vontobell, P., Beer, H. F., Leenders, K. L., Chaudhuri, K. Ray, Parker, J., Pye, I. F., Millac, P. A. H., Abbott, R. J., Sutter, M., Albani, C., de Rijk, M. C., Breteler, M. M. B., Graveland, G. A., van der Mechè, F. G. A., Hofman, A., Keipes, M., Hilger, Ch., Diederich, N., Metz, H., Hentges, F., Pollak, P., Benabid, A. L., Limousin, P., Hoffmann, D., Benazzouz, A., Perret, J., Laihinen, A., Rinne, J. O., Ruottinen, H., Nagren, K., Lehikoinen, P., Oikonen, V., Ruotsalainen, U., Rinne, U. K., Cocozza, S., Pizzuti, A., Cavalcanti, F., Monticelli, A., Pianese, L., Redolfi, E., Paiau, F., Di Donato, S., Pandolfo, M., Palau, F., Monros, E., De Michele, G., Smeyers, P., Lopez-ArLandis, J., Uilchez, J., Filla, A., Genis, D., Matilla, T., Volpini, V., Blanchs, M. I., Davalos, A., Molins, A., Rosell, J., Estivill, X., De Jonghe, P., Smeyers, G., Krols, L., Mercelis, R., Hazan, J., Weissenbach, J., Martin, J. J., Warner, T. A. T., Williams, L., Orb, A. S., Harding, A. E., Giunti, P., Sweeney, M. G., Spadaro, M., Jodice, C., Novelletto, A., Malaspina, P., Frontali, M., Salmon, E., Gregoire, Fiore, Del, Comar, Franck, G., Scheltens, P. H., Siegfried, K., Dartigues, E., De Deyn, P., Horn, R., Nelson, I., Hanna, M. G., Morgan-Hughes, J. A., Collinge, J., Palmer, M. S., Campbell, T., Mahal, S., Sidle, K., Humphreys, C., Tavitian, B., Pappata, S., Jobert, A., Crouzel, A. M., DiGiamberardino, L., Steimetz, G., Barbanti, P., Fabbrini, G., Salvatore, M., Buzzi, M. G., Di Piero, V., Petraroli, R., Sbriccoli, A., Pocchiari, M., Macchi, G., Lenzi, G. L., Spiegel, R., Maguire, P., Schmid, W., Ott, A., Bots, M. L., Grobbe, D. E., Hofman, A., Howard, R. S., Russell, S., Losseff, N., Hirsch, N. P., Couderc, R., Bailleul, S., Nargeot, M. C., Touchon, J., Picot, M. C., Rizzo, M., Watson, G., McGehee, D., Dingus, T., Kappos, L., Radü, E. W., Haas, J., Hartard, C. H., Spuler, S., Yousry, T., Voltz, R., Scheller, A., Holler, E., Hohlfeld, R., Scolding, N. J., Sussman, J., Kolar, O. J., Farlow, M. R., Rice, P. H., Zipp, F., Sotgiu, S., Weiss, E. H., Wekerle, H., Chalmers, R., Robertson, N., Compston, D. A. S., Martino, G., Clementi, E., Brambilla, E., Moiola, L., Martinelli, V., Colombo, B., Poggi, A., Rovaris, M., Grimaldi, L. M. E., Roth, M. P., Descoins, P., Ballivet, S., Ruidavets, J. B., Waubant, E., Nogueira, L., Cambon-Thomsen, A., Clanet, M., Leppert, D., Hauser, S., Lugaresi, A., Tartaro, A., D'aurelio, P., Befalo, L. L. O., Thomas, A., Malatesta, G., Gambi, D., Benedikz, J. E. G., Magnusson, H., Poser, C. M., Guomundsson, G., Bates, T. E., Davies, S. E. C., Clark, J. B., Landon, D. N., ùther, J. R., Rautenberg, W., Overgaard, K., Sereghy, T., Pedersen, H., Boysen, G., Diez-Tejedor, E., Carceller, F., Gutierrez, M., Lopez-Pajares, R., Roda, J. M., Chandra, B., Ricart, W., Gonzalez-Huix, F., Molina, A., Rundek, T., Demarin, V., De Reuck, J., Boon, P., Decoq, D., Strijckmans, K., Goethals, P., Lemahieu, I., Nibbio, A., Chabriat, H., Vahedi, K., Nagy, T., Verin, M., Mas, J. L., Julien, J., Ducrocq, X., Iba-Zizen, M. T., Cabanis, E. A., Bousser, M. G., Rolland, Y., Landgraf, F., Bompais, B., Lemaitre, M. H., Edan, G., Vorstrup, S., Knudsen, L., Olsen, K. Skovgaard, Videbaek, C., Schroeder, T., van Gijn, J., Jansen, H. M. L., Pruim, J., Paans, A. M. J., Willemsen, A. T. M., Hew, J. M., vd Vliet, A. M., Haaxma, R., Vaalburg, W., Minderhoud, J. M., Korf, J., Soudain, S. E., Ho, T. W., Mishu, B., Li, C. Y., Nachainkin, I., Gao, C. Y., Cornblath, D. R., Griffin, J. W., Asbury, A. K., Blaser, M. J., McKhann, G. M., Ho, T., Macko, C., Xue, P., Stadlan, E. M., Ramos-Alvarez, M., Valenciano, L., Visser, L. H., van der Meché, F. G. A., van Darn, P. A., Meulstee, J., Schmitz, P. I. M., Jacobs, B., Oomes, P. G., Kleyweg, R. P., Jacobs, B. C., Endtz, H. P., van Doorn, P. A., van der Mech, F. G. A., Van den Berg, L. H., Mollee, I., Logtenberg, T., Thomas, P. K., Plant, G., Baxter, P. J., Luis, R. Santiago, Matsumoto, M., Notermans, N. C., Wokke, J. H. J., Lokhorst, H. M., van der Graaf, Y., Jennekens, F. G. I., Azulay, J. P., Bille-Turg, F., Valentin, P., Farnarier, G. G., Pellissier, J. F., Serratrice, G., Quasthoff, S., Schneider, U., Grafe, P., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., van den Bent, M. J., Birklein, F., Spitzer, A., Lang, E., Neundorfer, B., Diehl, R. R., Lücke, D., Smith, G. D. P., Mathias, C. J., Serra, J., Campera, M., Ochoa, J. L., Ray Chaudhuri, K., Pavitt, D., Alam, M., Handwerker, H. O., Bleasdale-Barr, K., Smith, G., Murray, N. M. F., Hawkins, P., Pepys, M., Gellera, C., DiDonato, S., Taroni, F., Uncini, A., Di Muzio, A., Servidei, S., Silvestri, G., Lodi, R., Iotti, S., Barbiroli, B., Morrissey, S. P., Borruat, F. X., Francis, D., Mosely, I., Hansen, H. C., Helmke, K., Kunze, K., Sadzot, B., Maquet, P., Lemaire, Plenevaux, Damhaut, Sommer, C., Myers, R. R., Berta, E., Mantegazza, R., Argov, Z., Shapira, Y., Wirguin, I., Beuuer, J., Franke, C., Roberts, M., Willison, H., Vincent, A., Newsom-Davis, J., Morrison, K. E., Damels, R., Francis, M., Campbell, L., Davies, K. E., Kohler, W., Bucka, C., Hertel, G., Kanovsky, P., Auer, D., Ackermann, H., Klose, U., Naegele, Th., Bien, S., Voigt, K., Fink, G. R., Stephan, K. M., Wise, R. J. S., Mullatti, N., Hewer, L., Frackowiak, R. S. J., Weiller, C. S., Rijnites, M., Jueptner, M., Bauermann, T., Krams, M., Diener, H. C., van Walderveen, M. A. A., Barkhof, F., Hommes, O. R., Valk, J., Willmer, J. P., Guzman, D. A., Passingham, R. E., Silbersweig, D., Ceballos-Baumann, A., Frith, C. D., Frackowiak, R., Lucas, C. H., Goullard, L., Marchau, M. J., Godefroy, O., Rondepierre, P. H., Chamas, E., Mounier-Vehier, F., Leys, D., Renato, J., Verdugo, M. S. C., Campero, M., Jose, L., Ochoa, D. S. C., Vivancos, F., Tejedor, E. Diez, Martinez, N., Roda, J., Frank, A., Barreiro, P., Satoh, Y., Nagata, K., Maeda, T., Hirata, Y., YalÇinerner, B., Ozkara, C., Ozer, F., Ozer, S., Hanoglu, L., Zunker, P., Pozo, J. L., Oberwittler, C., Schick, A., Buschmann, H. -Ch., Ringelstein, E. Bernd, Lara, M., Anzola, G. P., Magoni, M., Volta, G. Dalla, Tarasov, A., Feigin, V., Beaudry, M. G., Carrier, S., Chicoutimi, Henriques, I. L., Bogoussslavsky, J., van Melle, G., Mathieu, J., Perusse, L., Allard, P., Prevost, C., Cantin, L., Bouchard, J. M., De Braekeleer, M., Agbo, C., Neau, J. P., Tantot, A. M., Dary-Auriol, M., Ingrand, P., Gil, R., Baltadjiev, D., Zekin, D., Sabey, K., Gennaula, C. P., Pope, B. A., Caparros-Lefebvre, D., Girard-Buttaz, I., Pruvo, J. P., Petit, H., Hipola, D., Martin, M., Giménez-Roldan, S., Ivanez, V., Japaridze, G., Carrasco, J. L., Picomell, I., Herranz, J. L., Macias, J. A., Nieto, M., Noya, M., Oller, L., Kiteva-Trencevska, G., Delgado, M. R., Liu, H., Luengo, A., Parra, J., Colas, J., Fernandez, M. J., Manzanares, R., Kornhuber, M. E., Malashkhia, V., Orkodashili, G., Martinez, M., Bonaventura, I., Porta, G., Martinez, I., Fernandez, A., Aguilar, M., Masnou, P., Drouet, A., Dreyfus, M., Cartron, J., Morel-Kopp, M. C., Tchernia, G., Kaplan, C., Lammers, M. W., Hekster, Y. A., Keyser, A., Meinardi, H., Renier, W. O., Boon, P. A. J. M., Have, M. D., Kint, B., Cruz, P., Cadilha, A., Almeida, R., Goncalves, M., Pimenta, M., Ramos, L. M. P., Polder, T. W., Broere, C. A., Polman, L., Rother, I., Rother, M., Schlaug, G., Arnold, S., Holthausen, H., Wunderlich, G., Ebner, A., Luders, H., Witte, O. W., Seitz, R. J., Serra, L. L., Gallicchio, B., Rotondi, F., Wieshmann, U., Meierkord, H., Sabev, K., Di Carlo, V., Gueguen, B., Derouesné, Ch., Ancri, D., Bourdel, M. C., Guillou, S., Aliaga, R., Chornet, M. A., Rodrigo, A., Pascual, A. Pascual -Leone, Catala, M. D., Pascual-Leone, A., Benbadis, S. R., Dinner, D. S., Chelune, G. J., Lüders, H. O., Piedmonte, M. R., Blanco, T., Lopez, M. P., Romero, B., Deltoro, A., Pascual, A., Pascual, Leone, Bolgert, F., Josse, M. O., Tassan, P., Touze, E., Laplane, D., Godenberg, F., Brizioli, E., Del Gobbo, M., Pelliccioni, G., Scarpino, O., Durak, H., Damlacik, G., Tunca, Z., Fidaner, H., Yurekli, Y., Yemez, B., Kaygisiz, A., Anllo, E. A., Esperet, E., Giovagnoli, A. R., Casazza, M., Spreafico, R., Avanzini, G., Mascheroni, S., Vecchio, I., Tornali, C., Antonuzzo, A., Grasso, A. A., Bella, R., Pennisi, G., Raffaele, R., Broeckx, J., Schildermans, F., Hospers, W., Deberdt, W., Carney, J. M., Aksenova, M., Chen, M. S., Juncadella, M., Busquets, N., De la Fuente, I., Rodriguez, A., Rubio, F., Soler, R., Khati, C., Pillon, B., Deweer, B., Malapani, C., Malichard, N., Dubois, B., Rancurel, G., Lopez, D. L., Jungreia, G., DeKosky, S. T., Boiler, F., Weiller, C., Rijntjes, M., Mueller, S. P., Maguire, E. A., Burke, E. T., Staunton, H., Phillips, J., Rousseaux, M., Pena, J., Bertran, I., Santacruz, P., Lopez, R., Catafau, A., Lomena, F., Blesa, R., Rampello, L., Nicoletti, A., Cabaret, M., Lesoin, F., Steinling, M., Tournev, I., Maier-Hauff, K., Schroeder, M., Wolf, A., Cochin, J. P., Noel, I., Augustin, P., Auzou, P., Hannequin, D., Maria, V., Lopez-Bresnahan, Danielle, D. M., Antin-Ozerkis, B. A., Bartels, E., Rodiek, S. O., Flugel, K. A., Campos, D. M., Salas-Puig, J., Del Rio, J. Sanhez, Vidal, J. A., Lahoz, C. H., Eraksoy, M., Barlas, O., Barlas, M., Bayindir, C., Ozcan, H., Birbamer, G., Gerstenbrand, F., Felber, S., Luz, G., Aichner, F., Seidel, G., Kaps, M., Hutzelmann, A., Gerriets, T., Kruggel, F., Martin, P. J., Gaunt, M. E., Abbot, R. J., Naylor, A. R., Meary, E., Dilouya, A., Meder, J. F., De Recondo, J., Lebtahi, R., Neff, K. W., Meairs, S., Viola, S., Matta, E., Aquilone, L., Rise, I. R., Authier, F. J., Kondo, H., Ghnassia, R. T., Degos, J. D., Gherardi, R. K., Bardoni, A., Ciafaloni, E., Comi, G. P., Bresolin, N., Robotti, M., Moggio, M., Rigoletto, C., Roses, A., Scarlato, G., Castelli, E., Turconi, A., Bresolin, N., Perani, D., Felisari, G., Chariot, P., de Pinieux, G., Astier, A., Jacotot, B., Gherardi, R., Fischer-Gagnepain, V., Louboutin, J. P., Crespo, F., Florea-Strat, A., Fromont, G., Sabourin, J. -C., Gonano, E. -F., Moroni, I., Prelle, A., Iannaccone, S., Quattrini, A., deRino, F., Sessa, M., Golzi, V., Smirne, S., Nemni, R., Turpin, J. C., Lucotte, G., Jacobs, S. C. J. M., Willems, P. W. A., Bootsma, A. L., Lasa, A., Calaf, M., Baiget, M., Gallano, B., Fichter-Gagnepain, V., Mazzucchelli, F., D'Angelo, M. G., Velicogna, M., Bet, L., Comi, G. P., Bordoni, A., Gonano, E. F., Bazzi, P., Rapuzzi, S., Moggio, M., Fagiolari, G., Ciscato, P., Messina, A., Battistel, A., Ryniewicz, B., Sangla, I., Desnuelle, C., Paquis, V., Cozzone, P. J., Bendahan, D., Sturenburg, H. J., Kohncke, G., Castellli, E., Linssen, W., Stegeman, D., Binkhorst, R., Notermans, S., Jaspert, A., Fahsold, R., de Munain, A. Lopez, Cobo, A., Martorell, L., Poza, J. J., Navarrete Palau, D., Emparanza, J. I., Sanchez-Roy, R., Vilchez, J. J., Hernandez, M., Tena, J. Garcia, Perla, C., Koutroumanidis, M., Papathanasopoulos, P., Papadimitriou, A., Papapetropoulos, T. H., Divari, R., Hadjigeorgiou, G. M., Anastasopoulos, I., Sansone, V., Rotondo, G., Meola, G., Rigoletto, C., Messina, S., Szwabowska-Orzeszko, E., Jozwiak, S., Michalowicz, R., Szaplyko, W., Petrella, M. A., Della Marca, G., Masullo, G., Mennuni, G. F., Kompf, D., Wascher, E., Verleger, R., Kaido, M., Soga, F., Toyooka, H., Bayon, C., Rubio, J., Carlomagno, S., Parlato, V., Santoro, A., Lavarone, A., Bonavita, V., Pentore, R., Venneri, A., Pasquier, F., Lebert, F., Grymonprez, L., Lefebvre, C., Van der Linden, M., Derouesné, C., Renault, B., Lacomblez, L., Homeyer, P., Ouss, L., Neuman, E., Malbezin, M., Barrandon, S., Guez, D., Stevens, M., van Swieten, J. C., Franke, C. L., Sanchez, A., Castellvirel, S., Mila, M., Jimenez, D., Pallesta, F., Ruiz, P. J. Garcia, Barrio, A., Barroso, T., Benitez, J., de Yebenes, J. Garcia, Manubens, J. M., Martinez-Lage, J. M., Larumbe, R., Muruzabal, J., Lacruz, F., Quesada, Pedro, Gallego, J., Ferini-Strambi, L., Marcone, A., Garancini, P., Tedesi, B., Jacob, B., Rozewicz, L., Langdon, D., Davie, C., Ron, M., Thompson, A., Koepp, M. J., Hansen, M. L., Guldin, B., Pressler, R. M., Ried, S., Scholz, C., Monaco, F., Gianelli, M., Schiavalla, M. P., Naldi, P., Cantello, R., Torta, R., Verze, L., Mutani, R., Knott, H., Ferbert, A., Schulze-Bonhage, A., Aust, W., Di Mascio, R., Marchioli, R., Vitullo, F., Di Pasquale, A., Sciulli, L., Kramer, V., Tognoni, G., Santacruz, P., Lopez, R., Marti, M. J., Charques, I., Catafau, A., Lomeila, F., Peila, J., Bertran, I., Blesa, R., Krendel, D. A., Costiga, D. A., Koeppen, S., Korn, W. M., Brugge, S., Schmitz, D., Scheulen, M. E., King, R. H. M., Robertson, A. M., Thomas, P. K., Kerkhofs, A., Vermersch, P., Dereeper, O., Daems Monpeun, C., Parent, M., Deplanque, D., Petit, H., Campero, M., Serra, J., Ochoa, J. L., Martinez-Matos, J. A., Montero, J., Olivé, M., Rene, R., Vidaller, A., Gugenheim, M., Gouider, R., Le Guern, E., Brice, A., Agid, Y., Bouche, P., Grisold, W., Ziflo, U., Drlicek, M., Budka, H., Jellinger, K., Zielinski, C. H., Ginsberg, L., King, R. H. M., Workman, J., Platts, A. D., Thomas, P. K., Gherardi, R. K., Florea-Strat, A., Poron, F., Sabourin, J. -C., Fazio, R., Nemni, R., Franceschi, M., Lorenzetti, I., Rinaldi, L., Canal, N., Weilbach, F. X., Sennlaub, A., Jung, S., Gold, R., Toyka, K. V., Hartung, H. P., Giegerich, G., Ellie, E., Vital, A., Steck, A. J., Vital, C., Julien, J., Doneda, P., Pizzul, S., Scarpini, E., Chiodi, P., Ramacci, M. T., Livraghi, S., Maimone, D., Annunziata, P., Salvadori, C., Guazzi, G. C., Arne-Bes, M. C., Delisle, M. B., Fabre, N., Hurtevent, J. F., Bes, A., Baudoin-Martin, D., Laborde, E., Viallet, F., Creisson, C., Crespi, V., Bogliun, G., Marzorati, L., Zincone, A., D'Angelo, L., Liberani, A., Merlini, M., Rivolta, R., Creange, A., Sabourin, J. -C., Theodorou, I., Gherardi, R. K., Conti, A. M., Malosio, M. L., Baron, P. L., Scarlato, G., Chorao, R., Rosas, M. J., Leite, I., Callea, L., Donati, E., Bargnani, C., Bud, M., Verdu, E., Navarro, X., Braun, S., Einius, S., Poindron, P., Warier, J. M., Bradley, J., Bekkelund, S. I., Torbergsen, T., Mellgren, S. I., Carlomagno, S., Parlato, V., Santoro, A., Lavarone, A., Boller, F., Bonavita, V., Engelhardt, A., Lörler, H., Robeck, S., Kluglein, C., Comi, G., Avoledo, V., Locatelli, T., Leocani, L., Galardi, G., Magnani, G., Medaglini, S., Chkhikvishvili, T. S., Zangaladze, A., Bratoeva, M., Kovachev, P., Chavdarov, D., Artemis, N., Karacostas, D., Milonas, I., Arpa, J., Lopez-Pajares, R., Cruz-Matinez, A., Sarria, J., Palomo, F., Alonso, M., Rodriguez-Al-barino, A., Lacasa, T., Nos, J., Barreiro, P., Martinez, A. Cruz, Villoslada, C., Alons, M., Taghavy, A., Hamer, H., Kratzer, A., Dethy, S., Pauwels, T., Monclus, M., Luxen, A., Goldman, S., Ziegler, M., Crambes, O., Ragueneau, I., Arnaud, F., Zappia, M., Montesanti, R., Colao, R., Palmieri, A., Branca, D., Nicoletti, G., Rizzo, M., Parlato, G., Quattrone, A., Vanacore, N., Zuchegna, P., Bonifati, V., Meco, G., Scholz, J., Friedrich, H. -J., Rohl, A., Ulm, G., Vieregge, P., Savettieri, G., Rocca, W. 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Martin, Fernandez, J., Mares, R., Torre, L., Mayayo, E., Lossos, A., Gomori, M., Libson, E., Goldfarb, A., Seigal, T., de Louw, A., Praamstra, P., Horstink, M., Cools, A., Tarrats, E. Basart, Calopa, M., Martinez, S., Ballabrina, J., Taussig, D., Marion, M. -H., Mallecourt, J., Ranoux, D., Gasser, T., Kabus, C., Ozelius, L., Wenzel, R., Breakefield, X. O., Boot, H., Poublon, R. M. L., Bogaard, J. M., GinaÏ, A. Z., Cabezas, C., Scholz, J., Nitschke, N., Vieregge, P., Wirk, B., Hochberg, F. H., Hefter, H., Kessler, K., Wirrwar, A., Stocklin, G., Tournier-Lasserves, E., Agundez, J. Garcia, Ruiz, E., Li, X. P., Hedlund, P. B., Fuxe, K., Kulisevsky, J., Avila, A., Berthier, M. L., Gerard, J. -M., Cambier, J., Caucheteur, C., Deuschl, G., Köster, B., Scheidt, C., Lücking, C. H., Mena, M. A., Chedru, F., Oubary, P., Rondot, P., Anagnostou, C. N., Panagopoulos, C. P., Ziogas, D. 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A., Del Ser, T., Ochoa, H. Severo, Munoz, D., Hachinski, V., Cucinotta, D., Senin, U., Girardello, R., Crepaldi, G., Croria, F., Schens, D. B., Vigo-Pelfrey, C., SempereE, A. P., Ortega, M. P., Bava, L., Magni, E., Aronovich, B. D., Treves, T. A., Bornstein, N. M., Van Blercom, N., Blecic, S., Violon, Ph., Hildebrand, J., Zamboni, M., Ambrosoli, L., Poli, A., Kuehnen, J., Tilgner, C., Raltzig, M., Moering, B., Faiss, J., Deeb, S. M. Al, Daif, A., Sharif, H., Tatay, J., Caroeller, F., Avendano, C., Vinogradova, T., Pinto, A. N., Canhao, P., Neau, J. -Ph., Pacquereau, J., Meurice, J. -C., Schwab, M., Bauer, R., Deeb, M. AL, Tjan, T. J., Aabed, M., Berges, S., Crepin-Leblond, T., Chavot, D., Cattin, F., Snidaro, M. H., Chopard, J. L., Ley, C. Oliveras, Alameda, F., Alfonso, S., Podobnik-Sarkanji, S., Pniewski, J., Torbicki, A., Mieszkowski, J., Plaza, I., Petrunjashev, V., Velcheva, I., Hadjiev, D., Yancheva, S., Petrov, L., Karakaneva, S., Petkov, A., Nikolov, E., Niehaus, L., Sacchetti, M. L., Toni, D., Fiorelli, M., Gori, C., Argentino, C., Lyrer, Ph., Radu, E. W., Gratzl, O., Rondepierre, Ph., Leclerc, X., Marchau, M., Scheltens, Ph., Hamon, M., Janssens, E., Henon, H., Lucas, C., KuÇukoglu, H., Baybas, S., Dervis, A., YalÇiner, B., Yilmaz, N., Ozturk, M., Arpaci, B., Navarro, J. A., Arenas, J., Perez-Sempere, A., Egido, J. A., Soriano-Soriano, C., Beau, P., Gergaud, J. -M., Coudero, C., Dierckx, R. A., Dobbeleir, A., Timmermans, E., Vandevivere, J., Lucas, C. H., Gomez, M., Aguirre, J., Berenguer, A., Duran, C., Parrilla, J., Gonzalez, F., Gironell, A., Rey, A., Marti-Vilalta, J. L., de Lecinana, M. Alonso, Federico, F., Conte, C., Simone, I. L., Giannini, P., Liguori, M., Lucivero, V., Picciola, E., Tortorella, C., Drislane, F., Wang, A. Ming, Di Mascio, R., Marchioli, R., Vitullo, F., Di Pasquale, A., Sciulli, L., Kramer, V., Tognoni, G., Levivier, M., del Olmo, A., Caballero, E., Degaey, I., de Bruijn, S. F. T. M., Tchaoussoglou, I., Bastianello, S., Pozzilli, C., Cervello, A., Catala, N., Koskas, F., Kieffer, E., Botia, E., Vivancos, J., Leon, T., Segura, T., Ramo, C., Lopez, F., Karepov, V. G., Gur, A. J., Berlanga, B., Gracia, V., Fiol, C., Kurtel, H., Ozkutlu, U., Yegen, B., Grau, A. J., Buggle, F., Heindle, S., Steichen-Wiehn, C., Banerjee, T., Maiwald, M., Becher, H., Villafana, W., Medina, F., Fernandez-Real, J. M., Soler, S., Planas, E., Iceman, E., Doganer, I., Badlan, G., Genc, B., Yulug, K., Ideman, E., Dural, H., Kutlul, K., Damalik, G., Baklan, Y., Metin, B., Tekinsoy, E., Iriarte, I., Subira, M. L., Crockar, A. D., Treacy, M., McNell, T. A., Grazzi, L., Ediboglu, N., Bilgin, H., Ertas, S., Goument, J. -P., Basset, C., Campos, Y., Garcia-Silva, T., Cabello, A., Bussaglia, E., Tizzano, E., Colomer, J., Gimbergues, P., Campagne, D., Bommelaer, C., Delaguillaume, B., Ramtami, H., Ait-Kaci-Ahmed, M., Pascual, L. F., Fernandez, T., Hortells, M., Sanz, C., Morales, F., Lauritzen, L., Picard, F., Sellal, F., Collard, M., Avramidis, T., Alexiou, E., Anastopoulos, T., Frongillo, D., Delfino, F. A., Cannata, M., Calo, L., Vichi, R., Antonini, G., Fragola, V., Cannata, D., Salas, M., Ruiz, C., Angelard, B., Lacau, J., Guily, St., Sendtner, M., Goadsby, Peter J., Quin, N. P., Gadian, D. G., Roland, P. E., Seitz, Rudiger J., Frackowiak, Richard S. J., Becker, G., Krone, A., Schmidt, K., Hofmann, E., Bogdahn, U., Rosenfeld, M. R., Meneses, P., Kaplitt, M. G., Dalmau, J., Posner, J., Cordon-Cardon, C., Hoang-Xuan, K., Vega, F., Nishisho, I., Moisan, J. P., Theillet, C., Delattre, O., Zhu, Jiahong, Walther, W., Posner, J. B., Roelcke, U., von Ammon, K., Pellikka, R., Lucking, C. H., Walon, C., Boucquey, D., -Van Rijckevorsel, K. Harmant, Lannoy, N., Verellen-Dunoulin, Ch., Liszka, U., Cavaletti, G., Casati, B., Kolig, C., Bogliun, G., Marzorati, L., Johannsen, L., Chio, A., Ruda, R., Vigliani, M. C., Sciolla, R., Seliak, D., Hoang-Xuang, K., Villanueva, J. A., Montalban, X., Arboix, A., Colosimo, C., Albanese, A., Hughes, A. J., de Bruin, V., Lees, A. J., Kowalski, J. W., Banfi, S., Santoro, L., Perretti, A., Castaldo, I., Barbieri, F., Campanella, G., Bhatia, K. P., Mardsen, C. D., de Bruin, V. S., Machedo, C., Ceballos-Baumann, D., Marsden, C. D., Brooks, D. B. J., Wennlng, G. K., Quinn, N., McDonald, W. l., Warner, T. T., Bain, P. C., Davis, M. B., Conway, D., Shaunak, S., O'Sullivan, E., Crawford, T., Lawden, M., Blunt, S., Rapoport, A., Sarova-Pinchas, I., de Beyl, D. Zegers, Mavroudakis, N., Blanc, S., Godinot, C., Lenoir, G., Barkhof, M. S. F., Tas, M. W., Baron, P. L., Constantin, C., Cassatella, M. A., Langdon, D. W., Webb, S., Gasparini, P., Zeviani, A., Kidd, D., Mammi, S., Cahalon, L., Hershkoviz, R., Lahat, N., Wallach, D., Annunziata, P., Martino, T., Maimone, D., Guazzi, G. C., Porrini, A. M., Dell'Arciprete, L., Rothwell, P. M., Stewart, R. R. C., Cull, R. E., Willmes, K., Poeck, K., Russell, D., Braekken, S. K., Brucher, R., Svennevig, J., Hermesl, M., Bruckmann, H., Biraben, A., Sliwka, U., Meyer, B., Schondube, F., Noth, J., Lavenu, I., Lammers, C., Waldecker, B., Haberbosch, W., Stam, J., Schneider, R., Gautier, J. C., Berlit, T. P., Fauser, B., Kuhne, D., Geraud, G., Danielli, A., Larrue, V., Bes, A., Timmerman, E., Bono, F., Bruni, A. C., Valalentino, P., Montesi, M. P., Talerico, G., Zappia, M., Sabatelli, M., Quattrone, A., Pareyson, D., Lorenzetti, D., Sghirlanzoni, A., Castellotti, B., Lupski, J. R., Archidiacono, N., Antonacci, R., Marzella, R., Rocchi, M., Samuel, D., Goulon-Goeau, C., Costa, P. P., Bismuth, H., Said, G., De Jongh, P., Lofgren, A., Timmerman, V., Vance, J. M., Van Broeckhoven, C., Martin, J. -J., Martinez, A. Cruz, Bort, S., Arpa, J., Misra, P., King, R. H. M., Badhia, K., Anderson, M., Caballo, A., Vichez, J., Gabriel, J. M., Erne, B., Miescher, G. C., Ulrich, J., Vital, A., Vital, C., Steck, A., Petry, K., Labatut, I., Hilmi, S., Ellie, E., Ferrini-Strambi, L., Zucconl, M., Marchettini, P., Palazzi, S., Oehlschlager, M., Pepinsky, R. B., Gemignani, F., Marbini, A., Pavesi, G., Di Vittorio, S., Manganelli, P., Mancia, D., Vermersh, P., Roche, J., Durocher, A. M., Dewailly, Ph., Dettmers, C., Fink, G., Lemon, R., Stephan, K., Passingham, D., Weder, B., Knorr, U., Huang, Y., Butterfield, D. A., Peris, M. L., Peiro, C., Pascual, A. Pascual-Leone, Bottini, G., Folnegovic-Smalc, V., Knezevic, S., Bokonjic, R., Ersmark, B., Torres, M. Gonzalez, Guiraud-Chaumeil, B., Haugaard, K., Jovicic, A., Chr, Lang, Levic, Z., Parra, C. Martinez, Ochoa, J. Patrignani, Titlbach, O., Wikkelso, C., Caparros-Lefevre, D., Debachy, B., Verier, A., Cantinho, G., Santos, A. I., Godinho, F., Bagunya, J., Roig, T., Ensenyat, A., Santiag, O., Trabucchi, H., De Leo, D., Koch, Ch., Zeumer, H., Matkovic, Z., Morris, P., Donaghy, M., Köhler, W., Kammer, T., Röther, J., Navon, R., Fontaine, B., Wu, Y., Capdevila, A., Guardiola, M. J., van Dijk, G. W., Notermans, N. C., Kruize, A. A., Kater, L., Bertelt, C., Hesse, S., Friedrich, H., Mauritz, K. -H., Giron, L. T., Watanabe, I. S., Ewing, D., Koepp, M., Lempert, T., Sander, B., Kauerz, U., Mehdorn, H. M., Hezel, J., Eickhoff, W., Kryst, T., Timsit, S., Gardeur, D., Reis, Mitermayer Galvao dos, Secor, E., Filho, A. Andrade, Silva, M. Cardoso, Santos, S. R. Silveira, Vasilaski, G., Reis, E. A. dos, Velupillai, P., Harn, D. A., Tigera, J. Garcia, Dreke, R. Martinez, Crespo, R. Piedra, Besses, C., Acin, P., Massons, J., Florensa, L., Oliveres, M., Sans-Sabrafen, J., Wicklein, E. M., Pleiffer, G., Kunre, K., Dieterich, M., Brandt, Th., Guarino, M., Stracciari, A., Pazzaglia, P., D'Alessandro, R., Santilli, I., and Donato, M.
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- 1994
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22. Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry
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Clarke, D. J., Brundin, P., Strecker, R. E., Nilsson, O. G., Björklund, A., and Lindvall, O.
- Abstract
Human fetal mesencephalic dopamine (DA) neurons, obtained from 6.5–9 week old aborted fetuses, were grafted to the striatum of immunosuppressed rats with 6-hydroxydopamine lesions of the ascending mesostriatal DA pathway. The effects on amphetamine-induced motor asymmetry were studied at various timepoints after grafting. At eight weeks, functional graft effects were not evident but after 11 weeks small effects on motor asymmetry could be monitored and rats tested 19–21 weeks after grafting exhibited full reversal of the lesion-induced rotational behaviour. Four rats were sacrificed at different timepoints between 8 and 20 weeks and the grafted DA neurons were studied in tyrosine hydroxylase (TH) immunocytochemically stained sections at the light and electronmicroscopic level. The grafts contained a total of 500–700 TH-positive neurons in each rat. In one rat sacrificed 8 weeks after grafting the grafted neurons were TH-positive but exhibited virtually no fiber outgrowth. In another rat, sacrificed after 11 weeks, a sparse TH-positive fiber plexus was seen to extend into the adjacent host neostriatum. Two rats sacrificed after 20 weeks both contained TH-positive neurons that gave rise to a rich fiber network throughout the entire host neostriatum, and this fiber network was also seen to extend into the globus pallidus and nucleus accumbens. Very coarse TH-positive processes, identified as dendrites in the electron microscope, projected up to 1.5–2.0 mm from the graft into the host striatum. Ultrastructural analysis revealed that the grafted neurons had formed no TH-positive synaptic contacts with host striatal neurons after 8 weeks, and at 11 weeks some few TH-positive synapses were identified. Twenty weeks after transplantation, abundant TH-positive synaptic contacts with host neurons were seen throughout the neostriatum, and such contacts were identified in the globus pallidus as well. Thus, the present study provides tentative evidence for a time-link between the development of synaptic contacts and the appearance of functional graft effects. Similar to the normal mesostriatal DA pathway, ingrowing TH-positive axons formed symmetric synapses and were mainly seen to contact dendritic shafts and spines. However, in comparison to the normal rat striatum there was a higher incidence of TH-immunoreactive boutons forming synapses onto neuronal perikarya. The TH-positive dendrites that extended into the host striatum were seen to receive non-TH-immunoreactive synaptic contacts, presumably arising from the host neurons. These results suggest that human fetal DA neurons are able to develop a reciprocal synaptic connectivity with the host rat when grafted to the adult brain. Grafting of human fetal DA neurons may therefore be expected to provide a means of restoring regulated synaptic DA release in patients with Parkinson's disease.
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- 1988
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23. Projections from the ventral tegmental area and mesencephalic raphe to the dorsal raphe nucleus in the rat
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Kalén, P., Skagerberg, G., and Lindvall, O.
- Abstract
The origins of the dopaminergic innervation of the rat dorsal raphe nucleus (NRD) have been investigated using a combination of fluorescent retrograde tracing and fluorescence histochemistry. Stereotaxic microinjections of True Blue were placed in the central, caudal and lateral portions of the NRD, and after 6–12 days survival the brains were processed for fluorescence histochemical detection of catecholamines. Retrogradely labeled neurons were searched for in the diencephalic A11 and A13 dopaminergic cell groups, substantia nigra, ventral tegmental area (VTA) and the linear, central superior and dorsal raphe nuclei. The various NRD injections consistently resulted in retrograde labeling of a small number of catecholamine-containing, presumed dopaminergic cell bodies, confined mainly to three regions: the VTA, the linear and central superior raphe nuclei and the NRD itself. The present findings indicate that not only dopaminergic neurons in the VTA but also the system of catecholamine-containing cells, extending dorsally and caudally from the VTA within the midline raphe area, project to the NRD. Although often similar in size, shape and distribution to the catecholaminergic neurons the majority of retrogradely labeled cells in these regions were, however, found to be non-catecholaminergic.
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- 1988
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24. Mechanisms of hypoglycemic brain damage
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Lindvall, O., Auer, R. N., and Siesjö, B. K.
- Abstract
Selective lesions of the noradrenergic locus coeruleus (LC) system have recently been shown to aggravate both ischemic and epileptic brain damage. This study explores the possibility that the LC system also influences hypoglycemic brain injury. Bilateral 6-hydroxydopamine lesions of the LC projection to the forebrain were found to cause no change in the degree of neuronal necrosis in the neocortex, hippocampal formation and caudateputamen following 30 min of reversible insulin-induced hypoglycemic coma. We propose that selective neuronal necrosis in ischemia and status epilepticus is due to the action of excitatory amino acids at synaptic sites, which can be partly counteracted by noradrenaline release from inhibitory LC terminals. In hypoglycemia, excitatory amino acids probably cause brain damage via a local and more diffuse toxic effect which is not significantly influenced by the activation of the LC system.
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- 1988
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25. Mechanisms of epileptic brain damage: evidence for a protective role of the noradrenergic locus coeruleus system in the rat
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Nevander, G., Ingvar, M., and Lindvall, O.
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This study explores the possibility that the noradrenergic locus coeruleus system influences epileptic brain damage. Bilateral 6-hydroxy-dopamine lesions of the locus coeruleus projection to the forebrain were found to aggravate neuronal necrosis in the neocortex following 60 min of flurothyl-induced status epilepticus. We propose that the activation of the inhibitory locus coeruleus system during status epilepticus counteracts a deleterious neuronal hyperexcitation, probably induced by excessive release of excitatory amino acids, thereby limiting neuronal necrosis.
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- 1986
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26. Selective lesions of mesostriatal dopamine neurons ameliorate hypoglycemic damage in the caudate-putamen
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Lindvall, O., Auer, R. N., and Siesjö, B. K.
- Abstract
Unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system was found to ameliorate neuronal necrosis in the caudate-putamen following 30 min of insulin-induced hypoglycemic coma. We propose that increased release of dopamine in the striatum during hypoglycemia or in the recovery period potentiates a deleterious neuronal hyperexcitation, probably induced by excessive release of glutamate or related compounds, thereby aggravating neuronal necrosis.
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- 1986
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27. Trophic and protective actions of brain-derived neurotrophic factor on striatal DARPP-32-containing neurons in vitro
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Nakao, N., Brundin, P., Funa, K., Lindvall, O., and Odin, P.
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- 1995
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28. Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma.
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Lindvall, O, Ernfors, P, Bengzon, J, Kokaia, Z, Smith, M L, Siesjö, B K, and Persson, H
- Abstract
In situ hybridization was used to study expression of mRNAs for members of the nerve growth factor (NGF) family in the rat brain after 2 and 10 min of forebrain ischemia and 1 and 30 min of insulin-induced hypoglycemic coma. Two hours after the ischemic insults, the level of brain-derived neurotrophic factor (BDNF) mRNA was markedly increased in the granule cells of the dentate gyrus, and at 24 h it was still significantly elevated. NGF mRNA showed a pronounced increase 4 h after 2 min of ischemia but had returned to a control level at 24 h. Both 2 and 10 min of ischemia caused a clear reduction of the level of mRNA for neurotrophin 3 (NT-3) in the dentate granule cells and in regions CA2 and medial CA1 of the hippocampus 2 and 4 h after the insults. The increase of BDNF mRNA could be partially blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX but was not influenced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Both NBQX and MK-801 attenuated the decrease of NT-3 mRNA after ischemia. One and 30 min of hypoglycemic coma also induced marked increases in BDNF and NGF mRNA in dentate granule cells with maximal levels at 2 h. If the changes of mRNA expression lead to alterations in the relative availability of neurotrophic factors, this could influence functional outcome and neuronal necrosis following ischemic and hypoglycemic insults.
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- 1992
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29. Epileptogenesis induced by rapidly recurring seizures in genetically fast- but not slow-kindling rats
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Elmer, E., Kokaia, M., Kokaia, Z., McIntyre, D. C., and Lindvall, O.
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- 1998
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30. Coexpression of neurotrophins and their receptors in neurons of the central nervous system.
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Kokaia, Z, Bengzon, J, Metsis, M, Kokaia, M, Persson, H, and Lindvall, O
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Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are neuronal survival molecules which utilize the Trk family of tyrosine kinase receptors. Using double-label in situ hybridization, we demonstrate that mRNAs for BDNF and its high-affinity receptor TrkB are coexpressed in hippocampal and cortical neurons. Also, a large number of neurons in these areas coexpress NGF and BDNF mRNAs. Epileptic seizures lead to increased levels of both BDNF/TrkB and NGF/BDNF mRNAs in double-labeled cells. Our results show that individual neurons of the central nervous system can coexpress neurotrophins and their receptors and produce two neurotrophic factors. These factors could support neuronal survival after brain insults, not only via retrograde transport but also through autocrine mechanisms.
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- 1993
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31. Seizure-induced differential expression of messenger RNAs for neurotrophins and their receptors in genetically fast and slow kindling rats
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Kokaia, Z., Kelly, M. E., Elmer, E., Kokaia, M., McIntyre, D. C., and Lindvall, O.
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- 1996
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32. Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain
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Funa, K., Yamada, N., Brodin, G., Pietz, K., Aahgren, A., Wictorin, K., Lindvall, O., and Odin, P.
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- 1996
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33. Phenotypic development of the human embryonic striatal primordium: a study of cultured and grafted neurons from the lateral and medial ganglionic eminences
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Grasbon-Frodl, E. M., Nakao, N., Lindvall, O., and Brundin, P.
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- 1996
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34. Expression of platelet-derived growth factor after intrastriatal ibotenic acid injury
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Sjöborg, M., Pietz, K., Åhgren, A., Yamada, N., Lindvall, O., Funa, K., and Odin, P.
- Abstract
Abstract: The expression of platelet-derived growth factor (PDGF) was studied in a rat model of Huntington’s disease, produced by unilateral intrastriatal ibotenic acid injections. The most pronounced effect registered was that the number of PDGF-immunoreactive cells increased in the lesioned area up to 10 weeks after the surgery. Double immunofluorescence staining indicated that the PDGF-positive cells were astrocytes. The increased PDGF immunoreactivity was associated with only minor changes in total PDGF mRNA and PDGF protein levels in the lesioned area. Reverse transcription–polymerase chain reaction (RT-PCR) demonstrated a slight increase in PDGF mRNA after ibotenic acid lesion, but this was not reflected in an increase in PDGF A- and B-chain protein concentration as measured with ELISA. After sham operation an increase in PDGF protein concentration was seen, while the number of PDGF-immunoreactive cells was unchanged. The accumulation of PDGF in the astrocytes might reflect the role of PDGF in a repair process in neurodegenerative processes.
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- 1998
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35. Evidence for new catecholamines or related amino acids in some invertebrate sensory neurons
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Elofsson, R., Falck, B., Lindvall, O., and Myhrberg, H.
- Abstract
In certain sensory neurons of many different invertebrate species, including the sea anemones. Metridium senile and Tealia felina and the crustacean Anemia salina, fluorophores are formed during the course of the fluorescent histochemical technique of Falck-Hillarp. The presumed catecholamine nature of the neuronal fluorogenic compound was investigated by microspectrofluorometry, and the spectral characteristics of the fluorescence in the taxonomically different species was found to be very similar (excitation maximum at 375 nm with a smaller peak or shoulder at 330 nm and sometimes a shoulder in the spectrum at 410 nm; emission maximum at 475 nm). The emission maximum coincides with that of the catecholamines and DOPA (475 nm). The excitation maximum (375 nm) directly after formaldehyde treatment, however, differs from that of the catecholamines and DOPA (410 nm), but is similar to the excitation maximum displayed by these catechol derivatives at acid pH. The spectral characteristics of the fluorophore in the sensory cells might therefore theoretically be explained by an acid pH in the cells. This seems improbable, however, and it is suggested that the phenomenon is due to the presence of unknown catechol derivatives. Analyses of the pH-dependent spectral changes indicate that the presumed catechol derivative in Tealia felina is ß-hydroxylated, whereas that in Anemia salina is not.
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- 1977
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36. Platelet-derived growth factor exerts trophic effects on rat striatal DARPP-32-containing neurons in culture
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Nakao, N., Brundin, P., Funa, K., Lindvall, O., and Odin, P.
- Abstract
The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat striatal neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.
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- 1994
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37. On the Occurrence of Cysteinyldopa and Dopa in Melanocytes and Benign Nevi Cells
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Falck, B., Jacobsson, S., Lindvall, O., and Nietsche, U. -B.
- Abstract
Previous studies have demonstrated a specific cytoplasmic fluorescence in human melanocytes, as well as in pigmented nevi and in malignant melanomas, when the formaldehyde histofluorescence method for visualization of certain catechol and indole derivatives was used. In malignant melanoma two fluorogenic substances, dopa and cysteinyldopa, were found previously. In human melanocytes and benign nevi cells the fluorogenic catechols have so far not been characterized, since chemical analyses are difficult to perform on skin, due to the small amounts of catechols present. However, using split thickness skin quantitative determinations are possible by sensitive fluorometric methods. The chemical analyses of cysteinyldopa showed that in human adult skin most or all was located in the superficial layers. The only specific fluorescence in the thin skin was found in dendritic melanocytes. The findings leave little doubt that cysteinyldopa is stored in melanocytes although the possibility of a concomitant occurrence of other thioethers is not excluded. Nevi and giant nevi were also similarly studied and we found considerable amounts of cysteinyldopa in the nevi. It seems as if the cysteinyldopa is stored in the fluorescent nevi cells. There was no consistent difference in the content of the catechol derivatives between intradermal and compound nevi.
- Published
- 1976
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38. Delayed kindling development after rapidly recurring seizures: relation to mossy fiber sprouting and neurotrophin, GAP-43 and dynorphin gene expression
- Author
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Elmer, E., Kokaia, M., Kokaia, Z., Ferencz, I., and Lindvall, O.
- Published
- 1996
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39. Seizure suppression in kindling epilepsy by intrahippocampal locus coeruleus grafts: evidence for an alpha-2-adrenoreceptor mediated mechanism
- Author
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Bengzon, J., Kokaia, M., Brundin, P., and Lindvall, O.
- Abstract
Intrahippocampal cell suspension grafts, prepared from the locus coeruleus region of rat fetuses, have previously been shown to retard seizure development in rats made hypersensitive to hippocampal kindling by a lesion of the forebrain noradrenergic system. The objective of the present study was to provide evidence that the seizure-suppressant effect elicited by the grafts is mediated via noradrenergic mechanisms. Two groups of rats received 6-hydroxydopamine in the lateral ventricle and then bilateral intrahippocampal locus coeruleus grafts. After 3 months, the grafted animals and a group of normal rats were subjected to hippocampal kindling. One group of grafted animals and the normal rats were injected intraperitoneally with the alpha-2 adrenergic receptor blocker idazoxan before each kindling stimulation. The other grafted rats received vehicle injections. The development of seizures was significantly faster in the grafted and normal rats that had been given idazoxan than in the grafted rats that had not been subjected to alpha-2 receptor blockade. Our data suggest that the seizure-suppressant action exerted by grafts of fetal locus coeruleus in hippocampal kindling is mediated via noradrenergic mechanisms, most likely via activation of postsynaptic alpha-2 adrenoreceptors.
- Published
- 1990
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40. Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture
- Author
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Nikkhah, G., Odin, P., Smits, A., Tingström, A., Othberg, A., Brundin, P., Funa, K., and Lindvall, O.
- Abstract
The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human TH-positive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as a trophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.
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- 1993
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41. Effects of cholinergic denervation on seizure development and neurotrophin messenger RNA regulation in rapid hippocampal kindling
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Ferencz, I., Kokaia, M., Keep, M., Elmer, E., Metsis, M., Kokaia, Z., and Lindvall, O.
- Published
- 1997
- Full Text
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42. Focal cerebral ischemia in rats induces expression of p75 neurotrophin receptor in resistant striatal cholinergic neurons
- Author
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Kokaia, Z., Andsberg, G., Martinez-Serrano, A., and Lindvall, O.
- Abstract
Expression of p75 neurotrophin receptor and survival of medium-sized spiny projection neurons and cholinergic interneurons in the rat striatum were studied using immunocytochemistry at different times after transient, unilateral middle cerebral artery occlusion. Thirty minutes of middle cerebral artery occlusion caused a major loss of projection neurons, identified by their immunoreactivity to dopamine- and adenosine 3′:5′-monophosphate-regulated phosphoprotein with a molecular weight of 32,000, in the lateral part of the striatum, as observed at 48 h following the insult with no further change at one week. In contrast, no reduction of the number of choline acetyltransferase-positive, cholinergic interneurons, which also expressed TrkA, was detected at either time-point. At 48 h following middle cerebral artery occlusion, expression of p75 neurotrophin receptor was observed in striatal cells which, by the use of double-label immunostaining, were identified as the cholinergic interneurons. No p75 neurotrophin receptor immunoreactivity remained in cholinergic cells after one week of reperfusion.
- Published
- 1998
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43. Dynamic changes of brain-derived neurotrophic factor protein levels in the rat forebrain after single and recurring kindling-induced seizures
- Author
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Elmer, E., Kokaia, Z., Kokaia, M., Carnahan, J., Nawa, H., and Lindvall, O.
- Published
- 1997
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44. Immunolesioning of basal forebrain cholinergic neurons facilitates hippocampal kindling and perturbs neurotrophin messenger RNA regulation
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Kokaia, M., Ferencz, I., Leanza, G., Elmér, E., Metsis, M., Kokaia, Z., Wiley, R.G., and Lindvall, O.
- Abstract
The immunotoxin 192 IgG-saporin induces an efficient and specific lesion of low-affinity nerve growth factor receptor-bearing cholinergic neurons in the basal forebrain. Intraventricular injection of 192 IgG-saporin, which caused a complete loss of cholinergic afferents to the hippocampus and neocortex and a partial denervation of amygdala and piriform cortex, was found to markedly facilitate the initial stages of seizure development in hippocampal kindling. In contrast, the progression of kindling process from focal to generalized seizures was not affected.In situ hybridization demonstrated that basal levels of brain-derived neutrotrophic factor messenger RNA in the hippocampal formation and piriform cortex were significantly decreased by the lesion, which also attenuated the seizure-induced increase of brain-derived neurotrophic factor messenger RNA expression in the hippocampus and frontal cortex. In the dentate gyrus, the 192 IgG-saporin lesion selectively reduced the upregulation of messenger RNAs for brain-derived neurotrophic factor exons I and III after a generalized seizure, whereas the increase of exon II messenger RNA was unchanged. The lesion abolished the seizure-evoked increase of nerve growth factor and TrkC messenger RNA levels and decrease of neutrophin-3 messenger RNA expression in dentate granule cells, while TrkB messenger RNA levels were not affected.
- Published
- 1996
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45. Grafted noradrenergic neurons suppress seizure development in kindling-induced epilepsy.
- Author
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Barry, D I, Kikvadze, I, Brundin, P, Bolwig, T G, Björklund, A, and Lindvall, O
- Abstract
Norepinephrine-rich cell suspensions, prepared from the locus coeruleus region of rat fetuses, were grafted bilaterally into the hippocampus of rats made hypersensitive to hippocampal kindling by a neurotoxic lesion of the central catecholamine system. The animals with grafts showed a marked suppression of the onset and progression of kindling-induced epilepsy, and this effect was correlated with the degree of graft-derived noradrenergic innervation of the host hippocampal formation. We conclude that grafted neurons can modulate the excitability of epileptic brain regions.
- Published
- 1987
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46. Letters to the editor: New principles for microspectrofluorometric differentiation between DOPA, dopamine and noradrenaline.
- Author
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Lindvall, O, Björklund, A, Falck, B, and Svensson, L A
- Published
- 1975
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47. Neurotrophic factors and brain ischemia
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Kokaia, Z. and Lindvall, O.
- Published
- 2001
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48. Monoamine--neuropeptide interactions
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Ho¨kfelt, T., Xu, Z.-Q.D., Holmberg, K., Kehr, J., Scho¨tt, P., O¨gren, S.O., Wang, F.H., Yoshitaki, T., Bartfai, T., Lendahl, U., Kokaia, M., Nanobashvili, A., Kokaia, Z., Lindvall, O., Kahl, U., and Yamaguchi, M.
- Published
- 2001
- Full Text
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49. First step towards cell therapy for Huntington's disease
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Lindvall, O and Björklund, A
- Published
- 2000
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50. FETAL DOPAMINE-RICH MESENCEPHALIC GRAFTS IN PARKINSON'S DISEASE
- Author
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Lindvall, O., Gustavii, B., Åstedt, B., Lindholm, T., Rehncrona, S., Brundin, P., Widner, H., Björklund, A., Leenders, K.L., Frackowiak, R., Rothwell, J.C., Marsden, C.D., Johnels, B., Steg, G., Freedman, R., Hopper, B.J., Seiger, Å., Strömberg, I., and Olson, M.BygdemanL.
- Published
- 1988
- Full Text
- View/download PDF
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