Abstract W MP39: Basic Fibroblast Growth Factor after Ischemic Stroke in Diabetic Patients - Research for Biomarkers in Ischemic Stroke (REBIOS)

Abstract

Background: In patients with diabetes mellitus (DM), functional outcome after ischemic stroke is poor. However, the precise mechanisms remain unclear. We hypothesized that basic fibroblast growth factor (bFGF), a neurotrophic/growth factor, does not function after ischemic stroke in DM patients compared with in non-DM ones. Methods and Results: We recruited 171 patients with ischemic stroke from the Fukuoka Stroke Registry, a prospective multi-centered study for acute stroke in Japan, and age- and sex- matched healthy subjects. Blood samples were obtained at five time points after the onset, day 0 (within 24 hours), 3, 7, 14 and 90. Plasma bFGF values were measured by Human MAP® v1.6, a multiplexed immunoassay (Myriad RBM, Inc.). Plasma bFGF was significantly higher in stroke patients at day 0 than in the controls (162.1 ± 21.0 vs. 91.0 ± 8.1 pg/ml, p = 0.001). The concentration of bFGF remained high during 90 days after onset. Unexpectedly, bFGF was significantly higher in patients with DM than in those without DM (180.8 ± 19.5 vs. 127.5 ± 13.1 pg/ml, p = 0.033), while the presence of DM did not associate with bFGF levels in healthy controls. Plasma bFGF was correlated positively with HbA1c ( p = 0.037), causal plasma glucose ( p = 0.048), and ICAM-1 ( p = 0.032) / VCAM-1 ( p = 0.086), representative adhesion molecules expressed in endothelial cells. In a mouse middle cerebral artery occlusion (MCAO) stroke model, bFGF expression in streptpzotocin-induced diabetic mice was significantly greater in ischemic hemisphere than in contralateral hemisphere. Immunohistochemical examination demonstrated that bFGF was expressed highly in vWF + endothelial cells, desmin + pericytes, and MAP2 + neurons, in peri-infarct areas after MCAO. Conclusion: Plasma bFGF was increased after ischemic stroke, which was prominent in DM patients. The presence of hyperglycemia in acute ischemic stroke may affect the expression of bFGF in various cell types in peri-infarct areas, which in turn may be associated with endothelial function, including the expression of adhesion molecules.