PMID- 15207263 OWN - NLM STAT- MEDLINE DCOM- 20040818 LR - 20061115 IS - 0969-9961 (Print) IS - 0969-9961 (Linking) VI - 16 IP - 1 DP - 2004 Jun TI - Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease. PG - 68-77 AB - We have investigated the effectiveness of transplantation of human neural stem cells into adult rat striatum prior to induction of striatal damage with the mitochondrial toxin 3-nitropropionic acid (3-NP). Systemic 3-NP administration caused widespread neuropathological deficits similar to ones found in Huntington disease (HD) including impairment in motor function (rotarod balance test) and extensive degeneration of neuron-specific nuclear antigen (NeuN)(+) neurons, calbindin(+) neurons and glutamic acid decarboxylase (GAD)(+) striatal neurons. Animals receiving intrastriatal implantation of human neural stem cells (hNSCs) 1 week before 3-NP treatments exhibited significantly improved motor performance and reduced damage to striatal neurons compared with control sham injections. In contrast, transplantation of hNSCs at 12 h after the initial 3-NP administration did not lead to any improvement in motor performance or protect striatal neurons from the 3-NP-induced toxicity. These results indicate that the presence of grafted hNSCs before 3-NP treatment is required for host striatal neuronal protection and enhanced motor function. Immunoreactivity of brain-derived neurotrophic factor (BDNF) was found in vitro in cultured hNSCs and in vivo in grafted NSCs with expression and secretion of BDNF demonstrated by RT-PCR, immunocytochemistry, dot-blot, and ELISA analyses. Thus, protective effects of proactive transplantation of hNSCs may be due, in part, to effects mediated by BDNF. The findings in this work have particular relevance to a rat model of HD in that proactive transplanted hNSCs protect host striatal neurons against neuronal injury and improve motor impairment induced by 3-NP toxicity. FAU - Ryu, Jae K AU - Ryu JK AD - Brain Disease Research Center, Ajou University School of Medicine, Suwon, South Korea. FAU - Kim, Jean AU - Kim J FAU - Cho, Sung J AU - Cho SJ FAU - Hatori, Kozo AU - Hatori K FAU - Nagai, Astushi AU - Nagai A FAU - Choi, Hyun B AU - Choi HB FAU - Lee, Min C AU - Lee MC FAU - McLarnon, James G AU - McLarnon JG FAU - Kim, Seung U AU - Kim SU LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 SB - IM MH - Animals MH - Cell Line, Transformed MH - Corpus Striatum/pathology/*transplantation MH - *Disease Models, Animal MH - Humans MH - Huntington Disease/pathology/*surgery MH - Male MH - Nerve Degeneration/pathology/*prevention & control/surgery MH - Neurons/*transplantation MH - Rats MH - Rats, Inbred Lew MH - Stem Cell Transplantation/*methods MH - Stem Cells/*physiology MH - Telencephalon/transplantation EDAT- 2004/06/23 05:00 MHDA- 2004/08/19 05:00 CRDT- 2004/06/23 05:00 PHST- 2003/05/14 00:00 [received] PHST- 2003/11/26 00:00 [revised] PHST- 2004/01/14 00:00 [accepted] PHST- 2004/06/23 05:00 [pubmed] PHST- 2004/08/19 05:00 [medline] PHST- 2004/06/23 05:00 [entrez] AID - S0969996104000142 [pii] AID - 10.1016/j.nbd.2004.01.016 [doi] PST - ppublish SO - Neurobiol Dis. 2004 Jun;16(1):68-77. doi: 10.1016/j.nbd.2004.01.016.