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Effect of soman poisoning on populations of bone marrow and peripheral blood cells in mice
Neurotoxicology, Issue: 1, Volume: 26, Pages: 89-98. | 2005-01-01
0 Patent citations    10 Scholarly citations     Reference Count: 22
Jean-Marc Collombet;Frederic Mourcin;Dominique Baubichon;Guy Lallement

摘要

Abstract According to recent reports, brain lesions resulting from ischemia, mechanical injury or neurodegenerative diseases can be partially treated using bone marrow-derived stromal cell (BMSC) engraftment approaches. Nevertheless, for brain lesions resulting from organophosphate poisoning, nerve agents such as soman (pinacolyl methylphosphono-fluoridate) could affect blood and bone marrow (BM) micro-environments, thus preventing efficient BMSC migration and engraftment. It is therefore necessary to verify the hematologic response to soman exposure. To assess this issue, the survival of BM cells, in particular hematopoietic progenitor and precursor cells (HPC), as well as distribution of the different populations of peripheral blood cells, were investigated in soman-intoxicated mice. Nine-week-old adult male B6D2F1 mice were treated with 110 μg/kg soman and 5.0 mg/kg methyl nitrate atropine. BM and peripheral blood (PB) samples were collected 1, 4, 8 and 22 days after poisoning. Various parameters were determined such as PB cell counting or, for BM samples, myelogram, in vitro colony-forming cells and phenotypic flow cytometry analysis. On post-soman day 1, a significant decrease in numbers of white blood cells and an increase in erythrocyte and platelet counts were noted. On post-soman day 4, the number of HPC decreased significantly, probably due to reduction of the replication rate of these immature cells. However, the number of more immature cells (Sca1+/Lin− phenotype) remained unchanged. On post-soman day 8 and day 22, the number of monocytes and granulocytes in the blood had considerably increased, probably due to a strong inflammatory reaction in response to soman poisoning. In conclusion, PB cell and BM-derived HPC populations are affected by acute soman poisoning, suggesting particular care, mainly for graft kinetic aspects, during future development of autologous BM stem cell therapy strategy to treat nerve agent-induced brain damage.


机构

Département de Toxicologie, CRSSA 24, Avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex, France. jmcollombet@crssa.netAix-Marseille UniversityCompuServeCompuServe


文献类型:

journal article;research support, non-u.s. gov't;

出版商:

Elsevier

发表时间:

2005-01-01

基金信息