Brain-derived neurotrophic factor in peripheral blood mononuclear cells and stroke outcome

Abstract

Stroke outcome is dependent on brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity. As peripheral blood mononuclear cells (PBMC) contain BDNF, diapedesis of these cells might be followed by BDNF delivery to the ischemic brain. To test this hypothesis, we investigated the association between BDNF levels in PBMC and functional outcome in patients with ischemic stroke. BDNF was measured in PBMC that were isolated from ischemic stroke patients (n = 40) just before (day 0) and after (days 1 and 3) fibrinolysis. Three months after stroke, patients were stratified using the modified Rankin Scale (mRS) according to the unfavorable (mRS scores 3–6) and favorable (mRS scores 0–2) functional outcome. We used univariate and multivariate logistic regressions to assess the relationship between BDNF levels in PBMC and functional outcome. BDNF levels in PBMC decreased from day 0 to day 3 in patients with unfavorable outcome, while they remained stable in patients with favorable outcome. Patients with favorable outcome exhibited at day 3 higher PBMC-BDNF levels than patients with unfavorable outcome and the levels were associated with good outcome (odd ratio: 12.0; 95% confidence interval, 1.4–106.2, P = 0.023). PBMC-BDNF levels remained a predictor of stroke outcome after adjusting from cardiovascular risk, interval between admission and fibrinolysis, stroke severity from hospital admission to discharge, lymphocytes count, neutrophils/lymphocytes ratio at admission. Favorable functional outcome in ischemic stroke patients that benefited from fibrinolysis was predicted by a high BDNF level in PBMC, suggesting that PBMC might serve as a cellular vector to deliver BDNF to the ischemic brain.

Impact statement

There are a great number of arguments suggesting that BDNF could be involved in stroke recovery dependent of neuroplasticity. Methods that can enhance BDNF levels in the ischemic brain could therefore have great clinical value. Peripheral blood mononuclear cells (PBMC) that contain BDNF and infiltrate early and sustainably the ischemic brain might be used as a cellular vector to deliver BDNF to the ischemic brain and consequently promote recovery. This work is important in this field to show if this BDNF derived from BDNF could exert a positive action on stroke recovery. Our main results showed that a high BDNF level at day 3 after hospital admission was associated with a 12.4 fold increase in favorable outcome after adjusting for still recognized prognostic markers. The new information in this field is this finding identifies PBMC as an attractive cellular vector to deliver BDNF to the ischemic brain.