Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies

Abstract

Background: Whereas brain-derived neurotrophic factor (BDNF) levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients.

Methods and results: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d) embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67) was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization.

Conclusion: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

Figure 1. Serum BDNF after stroke.

A) BDNF levels were serially measured before and 4 h, 24 h, 8 d after embolization in the “stroke 8 d_s” group (n = 10), B) Scatter plot between individual BDNF levels and degree of cerebral embolization according to the time of measurement of BDNF levels after embolization. Data are expressed as mean ± SD, BE = before embolization, r_s = Spearman's rank correlation coefficient

Figure 2. Plasma BDNF levels after stroke.

A) BDNF levels were serially measured before and 4 h, 24 h, 8 d after embolization in the “stroke 8 d” group (n = 10), B) Scatter plot between individual BDNF levels and degree of cerebral embolization according to the time of measurement of BDNF levels after embolization. Data are expressed as mean ± SD, BE = before embolization, r_s = Spearman's rank correlation coefficient

Figure 3. Brain BDNF levels after stroke.

A) brain was collected in control rats (empty bars, 7 rats) and in the “stroke 4 h”, “stroke 24 h”, and “stroke 8 d” groups (dashed bars, 10 rats per group), B). Scatter plot between levels of BDNF in individual brains and degree of cerebral embolization. Data are expressed as mean ± SD, * significantly different from control rats (p<0.016), r_s = Spearman's rank correlation coefficient.

Figure 4. Scatter plot between individual levels of BDNF in plasma (ng/mL) and brains (mg/g) that were simultaneously measured 4 h, 24 h, and 8 d after embolization in the “stroke 4 h”, “stroke 24 h”, and “stroke 8 d” groups (10 rats per group), respectively, r_s = Spearman's rank correlation coefficient.