Association of growth factors with arterial recanalization and clinical outcome in patients with ischemic stroke treated with tPA.
BACKGROUND
Growth factors (GF) such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and granulocyte-colony stimulating factor (G-CSF) have been associated with greater efficacy of tissue plasminogen activator (tPA) in experimental studies.


OBJECTIVE
To study the association of these GF with arterial recanalization and clinical outcome in patients with acute ischemic stroke treated with tPA.


METHODS
We prospectively studied 79 patients with ischemic stroke attributable to MCA occlusion treated with i.v. tPA within the first 3 h from onset of symptoms. Continuous transcranial color-coded sonography (TCCS) was performed during the first 2 h after tPA bolus to assess early MCA recanalization. Hemorrhagic transformation (HT) was classified according to ECASS II definitions. Good functional outcome was defined as a Rankin scale score of 0-2 at 90 days. GF levels were determined by ELISA.


RESULTS
Mean serum levels of VEGF, G-CSF and Ang-1 at baseline were significantly higher in patients with early MCA recanalization (n = 30) (all P < 0.0001). In the multivariate analysis, serum levels of VEGF (OR, 1.03), G-CSF (OR, 1.02) and Ang-1 (OR, 1.07) were independently associated with early MCA recanalization (all P < 0.0001). On the other hand, patients with parenchymal hematoma (PH) (n = 20) showed higher levels of Ang-1 (P < 0.0001). Ang-1 (OR, 1.12; P < 0.0001) was independently associated with PH, whereas patients with good outcome (n = 38) had higher levels of G-CSF (P < 0.0001). G-CSF was independently associated with good outcome (OR, 1.12; P = 0.036).


CONCLUSIONS
These findings suggest that GF may enhance arterial recanalization in patients with ischemic stroke treated with t-PA, although they might increase the HT.
Sobrino
T
T
Clinical Neuroscience Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain.
Millán
M
M
Castellanos
M
M
Blanco
M
M
Brea
D
D
Dorado
L
L
Rodríguez-González
R
R
Rodríguez-Yáñez
M
M
Serena
J
J
Leira
R
R
Dávalos
A
A
Castillo
J
J
D000368:Aged; D042683:Angiopoietin-1 / Q000819:agonists / Q000097:blood; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000819:agonists / Q000097:blood; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000819:agonists / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000097:blood
D042683:Angiopoietin-1; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D010959:Tissue Plasminogen Activator