{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:37:45Z","timestamp":1791902265498,"version":"4.3.4"},"reference-count":38,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,5]]},"abstract":"Object.<\/jats:italic> Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined the feasibility of convection-enhanced distribution of a neurotoxin by high-flow microinfusion to ablate the neurons of the GPm selectively and reverse experimental Parkinson's disease (akinesia, tremor, and rigidity).<\/jats:p>Methods.<\/jats:italic> Initially, to test the feasibility of this approach, the GPms of two naive rhesus macaques were infused with kainic acid or ibotenic acid through two cannulas that had been placed using the magnetic resonance imaging\u2014guided stereotactic technique. Two weeks later the animals were killed and their brains were examined histologically to determine the presence of neurons in the GPm and the integrity of the optic tract and the internal capsule. To examine the therapeutic potential of this paradigm, unilateral experimental Parkinson's disease was induced in six macaques by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and their behavior was studied for 12 weeks after chemopallidotomy was performed using kainic acid (three animals) or control infusion (three animals).<\/jats:p>Conclusions.<\/jats:italic> Chemopallidotomy using kainic acid permanently reversed the stigmata of MPTP-induced parkinsonism. By contrast, the control animals exhibited a transient recovery following intrapallidal infusion and then relapsed back to their baseline state. The use of high-flow microinfusion of selectively active toxins has the potential for treatment of Parkinson's disease and, by expanding the range of approachable targets to include large nuclei, for broad applications in clinical and experimental neuroscience.<\/jats:p>","DOI":"10.3171\/jns.1999.90.5.0928","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:21:50Z","timestamp":1242235310000},"page":"928-934","source":"Crossref","is-referenced-by-count":29,"title":["Reversal of experimental parkinsonism by using selective chemical ablation of the medial globus pallidus"],"prefix":"10.3171","volume":"90","author":[{"given":"Daniel M.","family":"Lieberman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Etienne","family":"Corthesy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Cummins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Oldfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Trends Neurosci","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/0166-2236(94)90092-2","article-title":"Neurotoxins: overview of an emerging research technology.","volume":"17","author":"Adams","year":"1994"},{"key":"b2","series-title":"Life Sci","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/0024-3205(86)90431-5","article-title":"Hemiparkinsonism in monkeys after unilateral internal carotid artery infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).","volume":"39","author":"Bankiewicz","year":"1986"},{"key":"b3","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3171\/jns.1994.81.6.0869","article-title":"Reversal of hemiparkinsonian syndrome in nonhuman primates by amnion implantation into caudate nucleus.","volume":"81","author":"Bankiewicz","year":"1994"},{"key":"b4","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"231","DOI":"10.3171\/jns.1990.72.2.0231","article-title":"The effect of fetal mesencephalon implants on primate MPTP-induced parkinsonism. Histochemical and behavioral studies.","volume":"72","author":"Bankiewicz","year":"1990"},{"key":"b5","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3171\/jns.1991.74.1.0097","article-title":"Fetal nondopaminergic neural implants in parkinsonian primates. Histochemical and behavioral studies.","volume":"74","author":"Bankiewicz","year":"1991"},{"key":"b6","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/ana.410400305","article-title":"Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study.","volume":"40","author":"Baron","year":"1996"},{"key":"b7","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0006-8993(80)90316-9","article-title":"The role of epileptic activity in hippocampal and \u201cremote\u201d cerebral lesions induced by kainic acid.","volume":"191","author":"Ben-Ari","year":"1980"},{"key":"b8","series-title":"Science","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1126\/science.2402638","article-title":"Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.","volume":"249","author":"Bergman","year":"1990"},{"key":"b9","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/0006-8993(94)90203-8","article-title":"Excitotoxic lateral pallidotomy does not relieve L-DOPA-induced dyskinesia in MPTP parkinsonian monkeys.","volume":"650","author":"Blanchet","year":"1994"},{"key":"b10","series-title":"J Pharmacol Exp Ther","first-page":"73","article-title":"Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion.","volume":"195","author":"Blasberg","year":"1975"},{"key":"b11","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":"b12","series-title":"Acta Neurochir","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1007\/BF01808881","article-title":"Gamma knife pallidotomy: case report.","volume":"139","author":"Bonnen","year":"1997"},{"key":"b13","series-title":"Neurobehav Toxicol Teratol","first-page":"611","article-title":"The neurophysiologic basis of abnormal movements in basal ganglia disorders.","volume":"5","author":"DeLong","year":"1983"},{"key":"b14","series-title":"Trends Neurosci","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0166-2236(90)90110-V","article-title":"Primate models of movement disorders of basal ganglia origin.","volume":"13","author":"DeLong","year":"1990"},{"key":"b15","series-title":"Appl Neurophysiol","first-page":"95","article-title":"Globus pallidus lesions in the monkey produced by kainic acid: histologic and behavioral effects.","volume":"42","author":"DeLong","year":"1979"},{"key":"b16","series-title":"J Neurophysiol","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1152\/jn.1985.53.2.530","article-title":"Primate globus pallidus and subthalamic nucleus: functional organization.","volume":"53","author":"DeLong","year":"1985"},{"key":"b17","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1002\/ana.410390416","article-title":"Gamma knife pallidotomy in advanced Parkinson's disease.","volume":"39","author":"Friedman","year":"1996"},{"key":"b18","series-title":"Acta Neurochir Suppl","first-page":"42","article-title":"The side-effects and complications of posteroventral pallidotomy.","volume":"68","author":"Hariz","year":"1997"},{"key":"b19","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3171\/jns.1997.87.1.0052","article-title":"Microelectrode-guided posteroventral medial radiofrequency pallidotomy for Parkinson's disease.","volume":"87","author":"Kopyov","year":"1997"},{"key":"b20","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3171\/jns.1992.76.1.0053","article-title":"Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease.","volume":"76","author":"Laitinen","year":"1992"},{"key":"b21","series-title":"Stereotact Funct Neurosurg","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1159\/000098965","article-title":"Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms.","volume":"58","author":"Laitinen","year":"1992"},{"key":"b22","series-title":"Nature","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/263797a0","article-title":"Polymers for the sustained release of proteins and other macromolecules.","volume":"263","author":"Langer","year":"1976"},{"key":"b23","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"586","DOI":"10.3171\/jns.1997.87.4.0586","article-title":"Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging.","volume":"87","author":"Laske","year":"1997"},{"key":"b24","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":"b25","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3171\/jns.1996.84.2.0194","article-title":"Methods for microelectrode-guided posteroventral pallidotomy.","volume":"84","author":"Lozano","year":"1996"},{"key":"b26","series-title":"Lancet","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1016\/S0140-6736(95)92404-3","article-title":"Effect of GPi pallidotomy on motor function in Parkinson's disease.","volume":"346","author":"Lozano","year":"1995"},{"key":"b27","series-title":"J Pharmacol Methods","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0160-5402(84)90031-7","article-title":"Drug distribution in solid tissue of the brain following chronic local perfusion utilizing implanted osmotic minipumps.","volume":"12","author":"Lum","year":"1984"},{"key":"b28","series-title":"J Pharm Sci","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/jps.2600750204","article-title":"Transport of cisplatin in rat brain following microinfusion: an analysis.","volume":"75","author":"Morrison","year":"1986"},{"key":"b29","series-title":"Am J Physiol","first-page":"R292","article-title":"High-flow microinfusion: tissue penetration and pharmacodynamics.","volume":"266","author":"Morrison","year":"1994"},{"key":"b30","series-title":"Nature","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/271676a0","article-title":"Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells.","volume":"271","author":"Nadler","year":"1978"},{"key":"b31","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/0006-8993(80)91289-5","article-title":"Loss and reacquisition of hippocampal synapses after selective destruction of CA3\u2013CA4 afferents with kainic acid.","volume":"191","author":"Nadler","year":"1980"},{"key":"b32","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"918","DOI":"10.3171\/jns.1990.73.6.0918","article-title":"Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone.","volume":"73","author":"Plunkett","year":"1990"},{"key":"b33","series-title":"Stereotact Funct Neurosurg","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000100662","article-title":"Gamma knife thalamotomy and pallidotomy in patients with movement disorders: preliminary results.","volume":"61","author":"Rand","year":"1993"},{"key":"b34","series-title":"Exp Brain Res","first-page":"443","article-title":"Magnetic resonance imaging of the rhesus monkey brain: use for stereotactic neurosurgery.","volume":"81","author":"Saunders","year":"1990"},{"key":"b35","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.3171\/jns.1996.85.6.1005","article-title":"Characteristics and somatotopic organization of kinesthetic cells in the globus pallidus of patients with Parkinson's disease.","volume":"85","author":"Taha","year":"1996"},{"key":"b36","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/0006-8993(85)90761-9","article-title":"Autoradiographic localization of kainic acid binding sites in the human hippocampus.","volume":"343","author":"Tremblay","year":"1985"},{"key":"b37","series-title":"Curr Opin Neurobiol","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/S0959-4388(96)80024-9","article-title":"Functional and pathophysiological models of the basal ganglia.","volume":"6","author":"Wichmann","year":"1996"},{"key":"b38","series-title":"Adv Neurol","first-page":"53","article-title":"Pathophysiology of parkinsonian motor abnormalities.","volume":"60","author":"Wichmann","year":"1993"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/90\/5\/article-p928.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/90\/5\/article-p928.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/90\/5\/article-p928.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T11:17:14Z","timestamp":1679915834000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/90\/5\/article-p928.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5]]},"references-count":38,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.3171\/jns.1999.90.5.0928","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[1999,5]]}}}