International journal of molecular sciences, 2018-05, Vol.19 (6), p.1635
2018
Details
- Autor(en) / Beteiligte
- Titel
- Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke
- Ist Teil von
- International journal of molecular sciences, 2018-05, Vol.19 (6), p.1635
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- When given beyond 4.5 h of stroke onset, tissue plasminogen activator (tPA) induces deleterious side effects in the ischemic brain, notably, hemorrhagic transformation (HT). We examined the efficacy of granulocyte-colony stimulating factor (G-CSF) in reducing delayed tPA-induced HT, cerebral infarction, and neurological deficits in a thromboembolic (TE) stroke model, and whether the effects of G-CSF were sustained for longer periods of recovery. After stroke induction, rats were given intravenous saline (control), tPA (10 mg/kg), or G-CSF (300 μg/kg) + tPA 6 h after stroke. We found that G-CSF reduced delayed tPA-associated HT by 47%, decreased infarct volumes by 33%, and improved motor and neurological deficits by 15% and 25%, respectively. It also prevented delayed tPA treatment-induced mortality by 46%. Immunohistochemistry showed 1.5- and 1.8-fold enrichment of the endothelial progenitor cell (EPC) markers CD34+ and VEGFR2 in the ischemic cortex and striatum, respectively, and 1.7- and 2.8-fold increases in the expression of the vasculogenesis marker von Willebrand factor (vWF) in the ischemic cortex and striatum, respectively, in G-CSF-treated rats compared with tPA-treated animals. Flow cytometry revealed increased mobilization of CD34+ cells in the peripheral blood of rats given G-CSF. These results corroborate the efficacy of G-CSF in enhancing the therapeutic time window of tPA for stroke treatment via EPC mobilization and enhancement of vasculogenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms19061635Titel-ID: cdi_doaj_primary_oai_doaj_org_article_1370d772cc65400fb11765915c1c65cc
- Format
- –
- Schlagworte
- Animals, Blood Cells - drug effects, Blood Cells - metabolism, Brain - blood supply, Brain - drug effects, Brain - pathology, CD34 antigen, Cells (biology), Cerebral infarction, Cerebral Infarction - drug therapy, Cerebral Infarction - etiology, Cerebral Infarction - prevention & control, Cerebrospinal fluid, Colonies, Colony-stimulating factor, Disease Models, Animal, Drug Synergism, Drug Therapy, Combination, Flow cytometry, G-CSF, Gene Expression, Granulocyte colony-stimulating factor, Granulocyte Colony-Stimulating Factor - administration & dosage, Granulocyte Colony-Stimulating Factor - adverse effects, Granulocyte Colony-Stimulating Factor - pharmacology, Granulocytes, Hemorrhage, Hemorrhage - drug therapy, Hemorrhage - etiology, Hemorrhage - prevention & control, hemorrhagic transformation, Immunohistochemistry, Infarction, Intravenous administration, Ischemia, Leukocytes (granulocytic), Male, Mortality, Neostriatum, Neurological diseases, Peripheral blood, Progenitor cells, Rats, Rodents, Stroke, Stroke - diagnosis, Stroke - drug therapy, Stroke - etiology, Stroke - mortality, t-Plasminogen activator, thromboembolic model, Thromboembolism, Time Factors, Tissue Plasminogen Activator - administration & dosage, Tissue Plasminogen Activator - adverse effects, Tissue Plasminogen Activator - pharmacology, tPA, Vascular Endothelial Growth Factor Receptor-2 - genetics, Vascular Endothelial Growth Factor Receptor-2 - metabolism, vasculogenesis, Von Willebrand factor, von Willebrand Factor - genetics, von Willebrand Factor - metabolism, Windows (intervals)