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Background and objectives: Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins. Low BDNF concentrations have been noted in patients with traditional cardiovascular disease risk factors and have been associated with the increased risk of stroke/transient ischemic attack (TIA). We aimed to study the correlation of BDNF serum levels with acute stroke severity and its potential role as a biomarker in predicting functional outcome. Materials and methods: We systematically searched PubMed, Web of Science, and the Cochrane database using specific keywords. The endpoints examined were the correlation of BDNF with functional outcome, the National Institute of Health stroke scale (NIHSS) measured at the acute phase, and stroke infarct volume. We also compared serum BDNF levels between stroke patients and healthy controls. Results: Twenty-six records were included from the initial 3088 identified. Twenty-five studies reported NIHSS and BDNF levels on the first day after acute stroke. Nine studies were further meta-analyzed. A statistically significant negative correlation between NIHSS and BDNF levels during the acute phase of stroke was noted (COR: −0.3013, 95%CI: (−0.4725; −0.1082), z = −3.01, p = 0.0026). We also noted that BDNF levels were significantly lower in patients with stroke compared to healthy individuals. Due to the heterogeneity of studies, we only conducted a qualitative analysis regarding serum BDNF and functional outcome, while no correlation between BDNF levels and stroke infarct volume was noted. Conclusions: We conclude that in the acute stroke phase, stroke severity is negatively correlated with BDNF levels. Concurrently, patients with acute stroke have significantly lower BDNF levels in serum compared to healthy controls. No correlations between BDNF and stroke infarct volume or functional outcome at follow-up were noted.

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