{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:27:59Z","timestamp":1790918879631,"version":"4.1.0"},"reference-count":37,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> A striatal dopamine lesion induces progressive nigral degeneration in rodents; however, intrastriatal injection of 6-hydroxydopamine (6-OHDA) causes only limited lesions due to spontaneous regeneration of the neurons that survive. To make an extensive lesion, the authors used a convection-enhanced delivery (CED) method for intrastriatal infusion of 6-OHDA and evaluated the animals for a model of Parkinson disease (PD).<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> Different doses of 6-OHDA were infused into the unilateral striatum in rats by using the CED method. The dopaminergic neuronal degeneration was evaluated based on morphological, biochemical, and behavioral measurements until 8 weeks postlesion.<\/jats:p>\n<jats:p content-type=\"fine-print\">Due to the wide distribution of the drug, CED of 20 \u00b5g of 6-OHDA into the striatum was sufficient to obtain a progressive and extensive nigrostriatal lesion as defined by morphological (&gt; 80% cell loss in the substantia nigra [SN]) and biochemical (&gt; 95% decrease in striatal dopamine) criteria. The extent of the lesion manifested as a stable turning behavior with amphetamine (&gt; 6 turns\/minute) and apomorphine (&gt; 4 turns\/minute). It also appeared that at 1 week postlesion the apoptotic markers were maximal in neurons of the SN.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> A rat model of PD with a progressive and extensive dopamine lesion was successfully made by intrastriatal CED of 6-OHDA. In this model, the therapeutic value can be assessed using behavioral, biochemical, and histochemical measurements. The delay of nigral neuronal death with respect to the time of 6-OHDA administration may provide a therapeutic window for testing neuroprotective strategies.<\/jats:p>","DOI":"10.3171\/jns.2003.98.1.0136","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:59:31Z","timestamp":1242237571000},"page":"136-144","source":"Crossref","is-referenced-by-count":28,"title":["Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease"],"prefix":"10.3171","volume":"98","author":[{"given":"Yoshitsugu","family":"Oiwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Sanchez-Pernaute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Harvey-White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krys S.","family":"Bankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Histol Histopathol","first-page":"25","article-title":"Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease.","volume":"12","author":"Anglade","year":"1997"},{"key":"b2","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1006\/exnr.2000.7408","article-title":"Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach.","volume":"164","author":"Bankiewicz","year":"2000"},{"key":"b3","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1073\/pnas.91.6.2076","article-title":"Convection-enhanced delivery of macromolecules in the brain.","volume":"91","author":"Bobo","year":"1994"},{"key":"b4","series-title":"Exp Brain Res","first-page":"1","article-title":"6-hydroxydopamine induces the loss of the dopaminergic phenotype in substantia nigra neurons of the rat. A possible mechanism for restoration of the nigrostriatal circuit mediated by glial cell line-derived neurotrophic factor.","volume":"111","author":"Bowenkamp","year":"1996"},{"key":"b5","series-title":"J Comp Neurol","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/cne.903550402","article-title":"Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons.","volume":"355","author":"Bowenkamp","year":"1995"},{"key":"b6","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/S0306-4522(98)00217-6","article-title":"Biochemical and anatomical characterization of forepaw adjusting steps in rat models of Parkinson's disease: studies on medial forebrain bundle and striatal lesions.","volume":"88","author":"Chang","year":"1999"},{"key":"b7","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3171\/jns.1999.90.2.0315","article-title":"Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time.","volume":"90","author":"Chen","year":"1999"},{"key":"b8","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1016\/S0021-9258(19)42751-8","article-title":"The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents.","volume":"249","author":"Cohen","year":"1974"},{"key":"b9","series-title":"Eur J Pharmacol","first-page":"329","article-title":"Inhibition of mitochondrial complexes I and IV by 6-hydroxydopamine.","volume":"292","author":"Glinka","year":"1995"},{"key":"b10","series-title":"J Neurosci Methods","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/0165-0270(94)90028-0","article-title":"Practical considerations for the use of the optical dissector in estimating neuronal number.","volume":"51","author":"Harding","year":"1994"},{"key":"b11","series-title":"Neurosci Lett","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0304-3940(94)90218-6","article-title":"Glial cell line-derived neurotrophic factor reverses toxin-induced injury to mid-brain dopaminergic neurons in vivo.","volume":"182","author":"Hoffer","year":"1994"},{"key":"b12","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"4929","DOI":"10.1523\/JNEUROSCI.18-13-04929.1998","article-title":"Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons.","volume":"18","author":"Horger","year":"1998"},{"key":"b13","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/0006-8993(91)90481-A","article-title":"Degeneration of the nigral dopaminergic neurons after 6-hydroxydopamine injection into the rat striatum.","volume":"549","author":"Ichitani","year":"1991"},{"key":"b14","series-title":"Neurodegeneration","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1006\/neur.1995.0016","article-title":"6-hydroxydopamine lesion of the rat substantia nigra: time course and morphology of cell death.","volume":"4","author":"Joen","year":"1995"},{"key":"b15","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"7111","DOI":"10.1523\/JNEUROSCI.17-18-07111.1997","article-title":"GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis.","volume":"17","author":"Kearns","year":"1997"},{"key":"b16","series-title":"Neurosci Lett","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0304-3940(96)13216-X","article-title":"Apoptotic neuron death in rat substantia nigra induced by striatal excitotoxic injury is developmentally dependent.","volume":"220","author":"Kelly","year":"1996"},{"key":"b17","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1006\/exnr.1998.6848","article-title":"Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat.","volume":"152","author":"Kirik","year":"1998"},{"key":"b18","series-title":"Exp Brain Res","first-page":"69","article-title":"Time course of striatal changes induced by 6-hydroxydopamine lesion of the nigrostriatal pathway, as studied by combined evaluation of rotational behavior and striatal Fos expression.","volume":"108","author":"Labandeira-Garcia","year":"1996"},{"key":"b19","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0006-8993(98)01290-6","article-title":"Kir6.2 oligoantisense administered into the globus pallidus reduces apomorphine-induced turning in 6-OHDA hemiparkinsonian rats.","volume":"818","author":"Lamensdorf","year":"1999"},{"key":"b20","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3171\/jns.1995.82.6.1021","article-title":"Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion.","volume":"82","author":"Lieberman","year":"1995"},{"key":"b21","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1523\/JNEUROSCI.19-04-01284.1999","article-title":"Distinct mechanisms underlie neurotoxin-mediated cell death in cultured dopaminergic neurons.","volume":"19","author":"Lotharius","year":"1999"},{"key":"b22","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"8117","DOI":"10.1073\/pnas.91.17.8117","article-title":"Apoptosis in substantia nigra following developmental striatal excitotoxic injury.","volume":"91","author":"Macaya","year":"1994"},{"key":"b23","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1523\/JNEUROSCI.17-06-02030.1997","article-title":"Early developmental destruction of terminals in the striatal target induces apoptosis in dopamine neurons of the substantia nigra.","volume":"17","author":"Marti","year":"1997"},{"key":"b24","series-title":"J Neurol Sci","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/0022-510X(95)00336-Z","article-title":"Histochemical detection of apoptosis in Parkinson's disease.","volume":"137","author":"Mochizuki","year":"1996"},{"key":"b25","series-title":"Development","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1242\/dev.116.1.201","article-title":"NeuN, a neuronal specific nuclear protein in vertebrates.","volume":"116","author":"Mullen","year":"1992"},{"key":"b26","series-title":"The Rat Brain in Stereotaxic Coordinates.","author":"Paxinos","year":"1986"},{"key":"b27","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1523\/JNEUROSCI.15-05-03775.1995","article-title":"Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models.","volume":"15","author":"Portera-Cailliau","year":"1995"},{"key":"b28","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/0306-4522(95)00066-R","article-title":"Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine.","volume":"67","author":"Przedborski","year":"1995"},{"key":"b29","series-title":"Eur J Neurosci","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1046\/j.1460-9568.1999.00566.x","article-title":"Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle.","volume":"11","author":"Rosenblad","year":"1999"},{"key":"b30","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/0306-4522(94)90605-X","article-title":"Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat.","volume":"59","author":"Sauer","year":"1994"},{"key":"b31","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"8935","DOI":"10.1073\/pnas.92.19.8935","article-title":"Glial cell line-derived neurotrophic factor but not transforming growth factor\u03b2 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.","volume":"92","author":"Sauer","year":"1995"},{"key":"b32","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/0006-8993(87)90691-3","article-title":"Selective loss of sub-populations of ventral mesencephalic dopaminergic neurons in the monkey following exposure of MPTP.","volume":"411","author":"Schneider","year":"1987"},{"key":"b33","series-title":"Am J Pathol","first-page":"119","article-title":"Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons.","volume":"150","author":"Tompkins","year":"1997"},{"key":"b34","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/0006-8993(70)90187-3","article-title":"Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system.","volume":"24","author":"Ungerstedt","year":"1970"},{"key":"b35","series-title":"Adv Neurol","first-page":"57","article-title":"Dopaminergic supersensitivity in the striatum.","volume":"9","author":"Ungerstedt","year":"1975"},{"key":"b36","series-title":"Anat Rec","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/ar.1092310411","article-title":"Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator.","volume":"231","author":"West","year":"1991"},{"key":"b37","series-title":"J Comp Neurol","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1002\/1096-9861(20001120)427:3<440::AID-CNE10>3.0.CO;2-7","article-title":"Time course of degenerative alterations in nigral dopaminergic neurons following a 6-hydroxydopamine lesion.","volume":"427","author":"Zuch","year":"2000"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/98\/1\/article-p136.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/98\/1\/article-p136.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/98\/1\/article-p136.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T19:54:48Z","timestamp":1679860488000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/98\/1\/article-p136.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":37,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3171\/jns.2003.98.1.0136","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[2003,1]]}}}