Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture.
The germinal matrix of human brain gives rise to oligodendrocytes and astrocytes after mid-gestation. Hemorrhage in the germinal matrix of premature infants is associated with suppressed cell proliferation. We hypothesize that soluble blood constituents have an adverse effect on the proliferation of cultured rat subventricular zone (SVZ) cells and the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPC). Using caspase 3 activation and lactate dehydrogenase release assays, rat plasma, serum, thrombin, and kallikrein killed SVZ cells when grown in the presence (but not absence) of platelet derived growth factor. Plasma and serum killed OPC at 1:1 to 1:100 dilutions. Using a bromodeoxyuridine incorporation assay OPC proliferation was reduced by plasma, serum, thrombin and plasmin. Blood proteins also suppressed OPC migration in a concentration dependent manner. However, differentiation of OPC into myelin basic protein expressing cells was suppressed only by thrombin. We conclude that soluble blood components, particularly thrombin, have an adverse effect on maturing SVZ cells and OPC derived from newborn rat brain.
Juliet
Packiasamy A R
PA
Department of Pathology, University of Manitoba and Manitoba Institute of Child Health Research, Winnipeg, Canada.
Frost
Emma E
EE
Balasubramaniam
Janani
J
Del Bigio
Marc R
MR
D000818:Animals; D000831:Animals, Newborn; D001769:Blood; D001921:Brain / Q000166:cytology; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010949:Plasma / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000737:chemistry; D013234:Stem Cells / Q000187:drug effects*
D005732:Gangliosides; D005904:Glial Fibrillary Acidic Protein; C062875:ganglioside A2B5; D007770:L-Lactate Dehydrogenase; D017493:Leukocyte Common Antigens; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine