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Quantitative histopathological assessments and pharmacological studies show that the ischemic spasticity is secondary to the loss of lumbar GABA and glycinergic inhibitory interneurons. In the present study, we investigated whether human hNT neurons or committed Sprague\u2013Dawley rat spinal neuronal precursors (SNPs) when grafted into previously ischemic spinal segments depleted of inhibitory neurons would restore local inhibitory tone and ameliorate spasticity. Rats with functionally and electrophysiologically defined spasticity that received spinal graft of hNT neurons or neuronal precursors and immunosuppressive treatment displayed a progressive recovery of motor function that correlated with the improvement of otherwise exacerbated peripheral motor response evoked by stimulation of motor cortex. In contrast, in control, medium\u2010injected or oligodendrocyte\u2010grafted animals no significant therapeutic effect was seen. Stereological quantification of grafted neurons revealed 1\u20132% survival at three months after transplantation. These surviving neurons displayed a robust axo\u2010dendritic sprouting and expression of markers typical of mature neurons including NSE, NeuN and synaptophysin. In both treatment groups a subpopulation of grafted neurons developed GABA immunoreactivity. These data provide evidence that a region specific grafting of hNT neurons or other neuronally committed cells, which have a potential to develop inhibitory neurotransmitter phenotype, represent an effective treatment modality to modulate ischemia\u2010induced spastic paraplegia.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2004.03702.x","type":"journal-article","created":{"date-parts":[[2004,11,3]],"date-time":"2004-11-03T11:40:12Z","timestamp":1099482012000},"page":"2401-2414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia"],"prefix":"10.1111","volume":"20","author":[{"given":"Martin","family":"Marsala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kakinohana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony L.","family":"Yaksh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Tomori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marsala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasa","family":"Cizkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,12]]},"reference":[{"key":"e_1_2_31_2_1","first-page":"147","article-title":"Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera\u20102. 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