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Changes in vascularization in substantia nigra pars compacta of monkeys rendered parkinsonian

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Summary.

The degeneration of nigral dopaminergic neurons in Parkinson’s disease is believed to be associated with a glial reaction and inflammatory changes. In turn, local factors may induce changes in vascularization and contribute to neuronal vulnerability. Among these factors, Vascular Endothelial Growth Factor (VEGF) is released in adults under pathological conditions and is thought to induce angiogenesis.

In order to determine whether changes in brain vasculature are observed in the affected brain regions in parkinsonism, we quantitatively analysed the VEGF-expressing cells and blood vessels in the substantia nigra of monkeys rendered parkinsonian by MPTP injection and compared the results with those obtained in control monkeys.

Using stereological methods, we observed an increase in the number of VEGF-expressing neurons and an increase of the number of blood vessels and their volume occupying the substantia nigra pars compacta of monkeys rendered parkinsonian by chronic MPTP intoxication. These changes in vascularization may therefore modify the neuronal availability of blood nutrients, blood cells or toxic substances and neuronal susceptibility to parkinsonism.

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References

  • C Barcia V Bautista A Sanchez-Bahillo E Fernandez-Villalba JM Navarro-Ruis AF Barreiro Y Poza M Poza MT Herrero (2003) ArticleTitleCircadian determinations of cortisol, prolactin and melatonin in chronic methyl-phenyl-tetrahydropyridine-treated monkeys. Neuroendocrinology 78 118–128 Occurrence Handle10.1159/000071967 Occurrence Handle12915764

    Article  PubMed  Google Scholar 

  • C Barcia V De Pablos V Bautista-Hernandez A Sanchez-Bahillo A Fernandez-Barreiro M Poza MT Herrero (2004a) ArticleTitleMeasurement of motor disability in MPTP-treated macaques using a telemetry system for estimating circadian motor activity. J Neurosci Methods 134 59–64 Occurrence Handle10.1016/j.jneumeth.2003.10.017

    Article  Google Scholar 

  • C Barcia A Sanchez Bahillo E Fernandez-Villalba V Bautista M Poza y Poza A Fernandez-Barreiro EC Hirsch MT Herrero (2004b) ArticleTitleEvidence of active microglia insubstantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure. Glia 46 402–409 Occurrence Handle10.1002/glia.20015

    Article  Google Scholar 

  • H Beck T Acker AW Puschel H Fujisawa P Carmeliet KH Plate (2002) ArticleTitleCell type-specific expression of neuropilins in an MCA-occlusion model in mice suggests a potential role in post-ischemic brain remodeling. J Neuropathol Exp Neurol 61 339–350 Occurrence Handle11939589

    PubMed  Google Scholar 

  • G Breier U Albrecht S Sterrer W Risau (1992) ArticleTitleExpression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114 521–532 Occurrence Handle1592003

    PubMed  Google Scholar 

  • MW Brightman (1965) ArticleTitleThe distribution within the brain of ferritin injected into cerebrospinal fluid compartments. II. Parenchymal distribution. Am J Anat 117 193–219 Occurrence Handle10.1002/aja.1001170204 Occurrence Handle5883189

    Article  PubMed  Google Scholar 

  • P Carmerliet KJ Rakesh (2000) ArticleTitleAngiogenesis in cancer and other diseases. Nature 407 249–257 Occurrence Handle10.1038/35025220 Occurrence Handle11001068

    Article  PubMed  Google Scholar 

  • D Casper SJ Engstrom GR Mirchandani A Pidel D Palencia PH Cho M Brownlee D Edelstein HJ Federoff WJ Sonstein (2002) ArticleTitleEnhanced vascularization and survival of neural transplants with ex vivo angiogenic gene transfer. Cell Transplant 11 331–349 Occurrence Handle12162374

    PubMed  Google Scholar 

  • JC Chavez F Agani P Pichiule JC LaManna (2000) ArticleTitleExpression of hypoxia-inducible factor-1alpha in the brain of rats during chronic hypoxia. J Appl Physiol 89 1937–1942 Occurrence Handle11053346

    PubMed  Google Scholar 

  • C Emanueli P Schratzberger R Kirchmair P Madeddu (2003) ArticleTitleParacrine control of vascularization and neurogenesis by neurotrophins. Br J Pharmacol 140 614–619 Occurrence Handle10.1038/sj.bjp.0705458 Occurrence Handle12970083

    Article  PubMed  Google Scholar 

  • EV Famiglietti EG Stopa ED McGookin P Song V LeBlanc BW Streeten (2003) ArticleTitleImmunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina. Brain Res 969 195–204 Occurrence Handle10.1016/S0006-8993(02)03766-6 Occurrence Handle12676380

    Article  PubMed  Google Scholar 

  • BA Faucheux N Nillesse P Damier G Spik A Mouatt-Prigent A Pierce B Leveugle N Kubis JJ Hauw Y Agid EC Hirsch (1995) ArticleTitleExpression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease. Proc Natl Acad Sci USA 92 9603–9607 Occurrence Handle7568181

    PubMed  Google Scholar 

  • BA Faucheux AM Bonnet Y Agid EC Hirsch (1999) ArticleTitleBlood vessels change in the mesencephalon of patients with Parkinson’s disease. Lancet 353 981–982 Occurrence Handle10.1016/S0140-6736(99)00641-8

    Article  Google Scholar 

  • JM Fearnley AJ Lees (1991) ArticleTitleAgeing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114 2283–2301 Occurrence Handle1933245

    PubMed  Google Scholar 

  • DL Felten KA Crutcher (1979) ArticleTitleNeuronal-vascular relationships in the raphe nuclei, locus coeruleus, and substantia nigra in primates. Am J Anat 155 467–481 Occurrence Handle10.1002/aja.1001550405 Occurrence Handle114041

    Article  PubMed  Google Scholar 

  • AM Graybiel CW Ragsdale SuffixJr (1978) ArticleTitleHistochemically distinct compartments in the striatum of human, monkeys, and cat demonstrated by acetylthiocholinesterase staining. Proc Natl Acad Sci USA 75 5723–5726 Occurrence Handle103101

    PubMed  Google Scholar 

  • MK Han M Kim SY Bae L Kang SY Han YS Lee JH Rha SU Kim JK Roh (2004) ArticleTitleVEGF protects human cerebral hybrid neurons from in vitro ischemia. Neuroreport 15 847–850 Occurrence Handle10.1097/00001756-200404090-00022 Occurrence Handle15073528

    Article  PubMed  Google Scholar 

  • A Hartmann S Hunot PP Michel MP Muriel S Vyas BA Faucheux A Mouatt-Prigent H Turmel A Srinivasan M Ruberg GI Evan Y Agid EC Hirsch (2000) ArticleTitleCaspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease. Proc Natl Acad Sci USA 97 2875–2880 Occurrence Handle10.1073/pnas.040556597 Occurrence Handle10688892

    Article  PubMed  Google Scholar 

  • T Hayashi K Abe H Suzuki Y Itoyama (1997) ArticleTitleRapid induction of vascular endothelial growth factor gene expression after transient middle cerebral artery occlusion in rats. Stroke 28 2039–2044 Occurrence Handle9341716

    PubMed  Google Scholar 

  • MT Herrero EC Hirsch A Kastner M Ruberg MR Luquin J Laguna F Javoy-Agid JA Obeso Y Agid (1993a) ArticleTitleDoes neuromelanin contribute to the vulnerability of catecholaminergic neurons in monkeys intoxicated with MPTP? Neuroscience 56 499–511 Occurrence Handle10.1016/0306-4522(93)90349-K

    Article  Google Scholar 

  • MT Herrero EC Hirsch A Kastner MR Luquin F Javoy-Agid LM Gonzalo JA Obeso Y Agid (1993b) ArticleTitleNeuromelanin accumulation with age in catecholaminergic neurons from Macaca fascicularis brainstem. Dev Neurosci 15 37–48

    Google Scholar 

  • MT Herrero I Perez-Otaño C Oset A Kastner EC Hirsch Y Agid MR Luquin JA Obeso J Del Rio (1993c) ArticleTitleGM-1 ganglioside promotes the recovery of surviving midbrain dopaminergic neurons in MPTP-treated monkeys. Neuroscience 56 965–972 Occurrence Handle10.1016/0306-4522(93)90142-3

    Article  Google Scholar 

  • EC Hirsch (1992) ArticleTitleWhy are nigral catecholaminergic neurons more vulnerable than other cells in Parkinson’s disease? Ann Neurol 32 S88–S93 Occurrence Handle10.1002/ana.410320715 Occurrence Handle1510386

    Article  PubMed  Google Scholar 

  • EC Hirsch BA Faucheux (1998) ArticleTitleIron metabolism and Parkinson’s disease. Mov Disord 13 39–45 Occurrence Handle10.1002/mds.870130111

    Article  Google Scholar 

  • E Hirsch AM Graybiel YA Agid (1988) ArticleTitleMelanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature 334 345–348 Occurrence Handle10.1038/334345a0 Occurrence Handle2899295

    Article  PubMed  Google Scholar 

  • S Hunot B Brugg D Ricard PP Michel MP Muriel M Ruberg BA Faucheux Y Agid EC Hirsch (1997) ArticleTitleNuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease. Proc Natl Acad Sci USA 94 7531–7536 Occurrence Handle10.1073/pnas.94.14.7531 Occurrence Handle9207126

    Article  PubMed  Google Scholar 

  • C Imbert E Bezard S Guitraud T Boraud CE Gross (2000) ArticleTitleComparison of eight clinical rating scales used for the assessment of MPTP-induced parkinsonism in the Macaque monkey. J Neurosci Methods 96 71–76 Occurrence Handle10.1016/S0165-0270(99)00184-3 Occurrence Handle10704673

    Article  PubMed  Google Scholar 

  • KL Jin XO Mao DA Greenberg (2000a) ArticleTitleVascular endothelial growth factor: direct neuroprotective effect in vitro ischemia. Proc Natl Acad Sci USA 97 10242–10247 Occurrence Handle10.1073/pnas.97.18.10242

    Article  Google Scholar 

  • KL Jin XO Mao DA Greenberg (2000b) ArticleTitleVascular endothelial growth factor rescues HN33 neural cells from death induced by serum withdrawal. J Mol Neurosci 14 197–203 Occurrence Handle10.1385/JMN:14:3:197

    Article  Google Scholar 

  • K Jin XO Mao SP Batteur E McEachron A Leahy DA Greenberg (2001) ArticleTitleCaspase-3 and the regulation of hypoxic neuronal death by vascular endothelial growth factor. Neuroscience 108 351–358 Occurrence Handle10.1016/S0306-4522(01)00154-3 Occurrence Handle11734367

    Article  PubMed  Google Scholar 

  • J Josko (2003) ArticleTitleCerebral angiogenesis and expression of VEGF after subarachnoid hemorrhage (SAH) in rats. Brain Res 981 58–69 Occurrence Handle10.1016/S0006-8993(03)02920-2 Occurrence Handle12885426

    Article  PubMed  Google Scholar 

  • MY Lee WK Ju JH Cha BC Son MH Chun JK Kang CK Park (1999) ArticleTitleExpression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats. Neurosci Lett 265 107–110 Occurrence Handle10.1016/S0304-3940(99)00219-0 Occurrence Handle10327180

    Article  PubMed  Google Scholar 

  • F Lennmyr KA Ata K Funa Y Olsson A Terent (1998) ArticleTitleExpression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat. J Neuropathol Exp Neurol 57 874–882 Occurrence Handle9737551

    PubMed  Google Scholar 

  • MR Luquin J Laguna MT Herrero JA Obeso (1993) ArticleTitleBehavioral tolerance to repeated apomorphine administration in parkinsonian monkeys. J Neurol Sci 114 40–44 Occurrence Handle10.1016/0022-510X(93)90046-2 Occurrence Handle8094427

    Article  PubMed  Google Scholar 

  • H Matsuzaki M Tamatani A Yamaguchi K Namikawa H Kiyama MP Vitek N Mitsuda M Tohyama (2001) ArticleTitleVascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity: signal transduction cascades. FASEB J 15 1218–1220 Occurrence Handle11344093

    PubMed  Google Scholar 

  • EG McGeer PL McGeer (1997) ArticleTitleThe role of the immune system in neurodegenerative disorders. Mov Disord 12 855–858 Occurrence Handle10.1002/mds.870120604 Occurrence Handle9399206

    Article  PubMed  Google Scholar 

  • J Naoumenko I Feigin (1974) ArticleTitleA simple silver solution for staining reticulin. Stain Technol 49 153–155 Occurrence Handle4135794

    PubMed  Google Scholar 

  • B Nico P Corsi A Vacca L Roncali D Ribatti (2002) ArticleTitleVascular endothelial growth factor and vascular endothelial growth factor receptor-2 expression in mdx mouse brain. Brain Res 953 12–16 Occurrence Handle10.1016/S0006-8993(02)03219-5 Occurrence Handle12384233

    Article  PubMed  Google Scholar 

  • OO Ogunshola A Antic MJ Donoghue SY Fan H Kim WB Stewart JA Madri LR Ment (2002) ArticleTitleParacrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. J Biol Chem 277 11410–11415 Occurrence Handle10.1074/jbc.M111085200 Occurrence Handle11777931

    Article  PubMed  Google Scholar 

  • Olzewski J, Baxter D (1954) Cytoarchitecture of the human brain stem. JB Lippincott, Philadelphia

  • HM Pinedo HM Verheul RJ D’Amato J Folkman (1998) ArticleTitleInvolvement of platelets in tumour angiogenesis? Lancet 352 1775–1777 Occurrence Handle10.1016/S0140-6736(98)05095-8 Occurrence Handle9848370

    Article  PubMed  Google Scholar 

  • TS Reese MJ Karnovsky (1967) ArticleTitleFine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34 207–217 Occurrence Handle10.1083/jcb.34.1.207 Occurrence Handle6033532

    Article  PubMed  Google Scholar 

  • W Risau (1997) ArticleTitleMechanisms of angiogenesis. Nature 386 671–674 Occurrence Handle10.1038/386671a0 Occurrence Handle9109485

    Article  PubMed  Google Scholar 

  • R Seljelid S Jozefowski B Sveinbjornsson (1999) ArticleTitleTumor stroma. Anticancer Res 19 4809–4822 Occurrence Handle10697594

    PubMed  Google Scholar 

  • WF Silverman JM Krum N Mani JM Rosenstein (1999) ArticleTitleVascular, glial and neuronal effects of vascular endothelial growth factor in mesencephalic explant cultures. Neuroscience 90 1529–1541 Occurrence Handle10.1016/S0306-4522(98)00540-5 Occurrence Handle10338318

    Article  PubMed  Google Scholar 

  • M Sondell M Kanje (2001) ArticleTitlePostnatal expression of VEGF and its receptor flk-1 in peripheral ganglia. Neuroreport 12 105–108 Occurrence Handle10.1097/00001756-200101220-00028 Occurrence Handle11201066

    Article  PubMed  Google Scholar 

  • M Sondell F Sundler M Kanje (2000) ArticleTitleVascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk-1 receptor. Eur J Neurosci 12 4243–4254 Occurrence Handle10.1046/j.0953-816X.2000.01326.x Occurrence Handle11122336

    Article  PubMed  Google Scholar 

  • DC Sterio (1984) ArticleTitleThe unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134 127–136 Occurrence Handle6737468

    PubMed  Google Scholar 

  • J Stone A Itin T Alon J Pe’er H Gnessin T Chan-Ling E Keshet (1995) ArticleTitleDevelopment of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 15 4738–4747 Occurrence Handle7623107

    PubMed  Google Scholar 

  • E Tischer R Mitchell T Hartman M Silva D Gospodarowicz JC Fiddes JA Abraham (1991) ArticleTitleThe human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266 11947–11954 Occurrence Handle1711045

    PubMed  Google Scholar 

  • GD Yancopoulos D Davis NW Gale JS Rudge SJ Wiegand J Holash (2000) ArticleTitleVascular-specific growth factors and blood vessels formation. Nature 407 242–248 Occurrence Handle10.1038/35025215 Occurrence Handle11001067

    Article  PubMed  Google Scholar 

  • T Yasuhara T Shingo K Kobayashi A Takeuchi A Yano K Muraoka T Matsui Y Miyoshi H Hamada I Date (2004) ArticleTitleNeuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease. Eur J Neurosci 19 1494–1504 Occurrence Handle10.1111/j.1460-9568.2004.03254.x Occurrence Handle15066146

    Article  PubMed  Google Scholar 

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Barcia, C., Bautista, V., Sánchez-Bahillo, Á. et al. Changes in vascularization in substantia nigra pars compacta of monkeys rendered parkinsonian. J Neural Transm 112, 1237–1248 (2005). https://doi.org/10.1007/s00702-004-0256-2

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