PMID- 20969864 OWN - NLM STAT- MEDLINE DCOM- 20110204 LR - 20161125 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 227 IP - 1 DP - 2011 Jan TI - Survival and differentiation of neuroectodermal cells with stem cell properties at different oxygen levels. PG - 136-48 LID - 10.1016/j.expneurol.2010.10.004 [doi] AB - Freeze-lesioned regions of the forebrain cortex provide adequate environment for growth of non-differentiated neural progenitors, but do not support their neuron formation. Reduced oxygen supply, among numerous factors, was suspected to impair neuronal cell fate commitment. In the present study, proliferation and differentiation of neural stem/progenitor cells were investigated at different oxygen levels both in vitro and in vivo. Low (1% atmospheric) oxygen supply did not affect the in vitro viability and proliferation of stem cells or the transcription of "stemness" genes but impaired the viability of committed neuronal progenitors and the expression of proneural and neuronal genes. Consequently, the rate of in vitro neuron formation was markedly reduced under hypoxic conditions. In vivo, neural stem/progenitor cells survived and proliferated in freeze-lesioned adult mouse forebrains, but did not develop into neurons. Hypoperfusion-caused hypoxia in lesioned cortices was partially corrected by hyperbaric oxygen treatment (HBOT). HBOT, while reduced the rate of cell proliferation at the lesion site, resulted in sporadic neuron formation from implanted neural stem cells. The data indicate that in hypoxic brain areas, neural stem cells survive and proliferate, but neural tissue-type differentiation can not proceed. Oxygenation renders the damaged brain areas more permissive for tissue-type differentiation and may help the integration of neural stem/progenitor cells. CI - 2010 Elsevier Inc. All rights reserved. FAU - Zadori, Anita AU - Zadori A AD - Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083 Szigony u. 43, Budapest, Hungary. FAU - Agoston, Viktor Antal AU - Agoston VA FAU - Demeter, Kornel AU - Demeter K FAU - Hadinger, Nora AU - Hadinger N FAU - Varady, Linda AU - Varady L FAU - Kohidi, Timea AU - Kohidi T FAU - Gobl, Anna AU - Gobl A FAU - Nagy, Zoltan AU - Nagy Z FAU - Madarasz, Emilia AU - Madarasz E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101020 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Antineoplastic Agents) RN - 0 (Hif1a protein, mouse) RN - 0 (Homeodomain Proteins) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Nanog Homeobox Protein) RN - 0 (Nanog protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (SOXB1 Transcription Factors) RN - 0 (Sox2 protein, mouse) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 5688UTC01R (Tretinoin) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacology MH - Behavior, Animal MH - Cell Differentiation/*drug effects/physiology MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects/physiology MH - Cell Transplantation/physiology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation/drug effects/physiology MH - Green Fluorescent Proteins/genetics MH - Homeodomain Proteins/metabolism MH - Hyperbaric Oxygenation/methods MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Hypoxia-Ischemia, Brain/pathology/surgery MH - Locomotion/physiology MH - Male MH - Mice MH - Models, Biological MH - Nanog Homeobox Protein MH - Nerve Tissue Proteins/metabolism MH - Neural Plate/cytology MH - Neuroepithelial Cells/*drug effects MH - Oxygen/metabolism/*pharmacology MH - SOXB1 Transcription Factors/metabolism MH - Stem Cells/drug effects/*physiology MH - Time Factors MH - Transfection/methods MH - Tretinoin/pharmacology EDAT- 2010/10/26 06:00 MHDA- 2011/02/05 06:00 CRDT- 2010/10/26 06:00 PHST- 2010/04/15 00:00 [received] PHST- 2010/10/06 00:00 [revised] PHST- 2010/10/12 00:00 [accepted] PHST- 2010/10/26 06:00 [entrez] PHST- 2010/10/26 06:00 [pubmed] PHST- 2011/02/05 06:00 [medline] AID - S0014-4886(10)00389-4 [pii] AID - 10.1016/j.expneurol.2010.10.004 [doi] PST - ppublish SO - Exp Neurol. 2011 Jan;227(1):136-48. doi: 10.1016/j.expneurol.2010.10.004. Epub 2010 Oct 20.