Bone marrow stromal cells increase astrocyte survival via upregulation of phosphoinositide 3-kinase/threonine protein kinase and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways and stimulate astrocyte trophic factor gene expression after anaerobic insult.
Transplantation of bone marrow stromal cells improves animal neurological functional recovery after stroke. Astrocytes are known to provide structural, trophic and metabolic support for neurons. Thus astrocytes are critical for neural survival during post-ischemia. However, information on the effects of bone marrow stromal cells on astrocytic survival post-ischemia is unavailable. We investigated the influence of rat bone marrow stromal cells on rat astrocytic apoptosis and survival post-ischemia employing an anaerobic chamber. Our data indicate that rat bone marrow stromal cells reduce cell death and apoptosis, and increase the DNA proliferation rate in astrocytes post-ischemia. Mitogen-activated protein kinase kinase/extracellular signal regulated kinase and phosphoinositide 3-kinase/threonine protein kinase pathways are involved in cell survival. Western blot showed that rat bone marrow stromal cells activate these two pathways in astrocytes post-ischemia, and upregulate total extracellular signal regulated kinase 1/2 and threonine protein kinase. Since astrocytes produce various neurotrophic factors, we performed reverse transcription polymerase chain reaction to investigate rat bone marrow stromal cells' effect on astrocyte growth factor gene expression post-ischemia. We observed that brain-derived neurotrophic factor, vascular endothelial growth factor and basic fibroblast growth factor gene expression was enhanced by rat bone marrow stromal cell coculture. These data suggest that bone marrow stromal cells increase astrocytic survival post-ischemic injury. This protective function might involve the activation of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/threonine protein kinase pathways. Upregulation of brain-derived neurotrophic factor, vascular endothelial growth factor and basic fibroblast growth factor may also contribute to astrocyte survival.
Gao
Q
Q
Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Li
Y
Y
Chopp
M
M
D000693:Anaerobiosis; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001562:Benzimidazoles; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000502:physiology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005456:Fluorescent Dyes; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D001562:Benzimidazoles; D019208:Brain-Derived Neurotrophic Factor; D001973:Bromodeoxyuridine; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D048049:Extracellular Signal-Regulated MAP Kinases; D016222:Fibroblast Growth Factor 2; D005456:Fluorescent Dyes; D006133:Growth Substances; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D012313:RNA; D042461:Vascular Endothelial Growth Factor A; C505410:Casp3 protein, rat; C017807:bisbenzimide ethoxide trihydrochloride