Circulating and Brain BDNF Levels in Stroke Rats. Relevance to Clinical Studies

Abstract

BackgroundWhereas 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 ResultsUnilateral 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.ConclusionCirculating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

Associations of BDNF Genotype and Promoter Methylation with Acute and Long-Term Stroke Outcomes in an East Asian Cohort

“…The crucial role of BDNF in stroke recovery has been repeatedly suggested in animal studies in that brain BDNF is increased in cerebral ischemia [21], [22], motor function improvement is associated with BDNF upregulation [23], and BDNF administration improves sensory motor recovery [3], [24], [25], whereas BDNF blockade prevents recovery [5], [26]. However, this hypothesis has been controversial in human research, in that no significant increase in blood BDNF levels were found after stroke [27], and associations between the BDNF met allele and ischemic stroke outcomes were not found to be significant [6], [7], although significant associations have been found in aneurismal subarachnoid haemorrhage [8], [9].…”

Post-stroke infections exacerbate ischemic brain injury in middle-aged rats: Immunomodulation and neuroprotection by progesterone

“…In contrast, others argue that changes in regional brain BDNF levels are not associated with changes in plasma or serum (Elfving et al, 2010; Luo et al, 2010). One recent study suggests that circulating BDNF levels do not mirror brain BDNF levels after permanent stroke, and severe stroke is associated with high plasma BDNF in the very acute stage (Bejot et al, 2011). However, this study has the limitation that the stroke model used lacked reperfusion after the initial blockage, so the data may apply only to patients or experimental subjects lacking reperfusion.…”

Neurotrophin-Induced Migration and Neuronal Differentiation of Multipotent Astrocytic Stem Cells In Vitro

“…BDNF is an important factor during brain development [32] and provides a directional cue that promotes the migration of cerebellar granular cells [36]. We found evidence that BDNF concentrations are increased after neonatal HI (unpublished data) as well as in the post-stroke milieu [37]. Researchers have postulated that BDNF increases the migration of stem cells [38], [39].…”

“…Another important consideration is the potential interaction between different neurotrophins. For example, in vitro experiments demonstrated that GDNF-induced branching of cultured ciliary neurons could be inhibited by BDNF [37]. Therefore, before researchers use neurotrophins together, they should test for potential interactions.…”