Abstract
Stroke is accompanied by severe inflammation in the brain. The role of mature brain-derived neurotrophic factor (mBDNF) in ischemic stroke has received intensive attention, but the function of its precursor proBDNF is less understood. Recent studies showed that mBDNF and proBDNF in the ischemic brain are upregulated, but the significance of mBDNF and proBDNF in the lymphocytes in ischemic stroke is not known. Here, we propose that the expression levels of mBDNF and proBDNF in lymphocytes correlate with those in the brain after ischemic stroke and therefore can be surrogate markers for the ischemic brain. Using a photothrombotic model in rats and ELISA assay technique, we found that proBDNF and mBDNF in peripheral lymphocytes were upregulated but produced differential time courses after ischemia. The levels of mBDNF and proBDNF in lymphocytes at early stages of stroke (1 day), showed a strong positive correlation with those in the brain. The levels of p75, sortilin, were also increased in a time-dependent manner after ischemic stroke; however, the levels of p-TrkB in the ischemic brain at 6 h, 1 and 3 days were significantly reduced in the brain. The present study suggests that the levels of proBDNF and mBDNF in the blood lymphocytes in acute ischemic stroke reflect those in the brain at early stages.
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Funding
This work was supported by NHMRC and the National Natural Science Foundation of China (81760064, 81360128) and the Natural Science Foundation of Yun Nan Province (2017FE467-163,2017FE467-025,2017FE467-160,U0120170515).
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All experimental procedures involving animals were approved by the Animal Ethics Committee of SA Pathology (Project U16/14) and conducted between 7 a.m. and 7 p.m. in accordance with the guidelines of the National Health and Medical Research Council of Australia. Rats were acclimatized for a week before any procedures were initiated.
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Luo, HY., Rahman, M., Bobrovskaya, L. et al. The Level of proBDNF in Blood Lymphocytes Is Correlated with that in the Brain of Rats with Photothrombotic Ischemic Stroke. Neurotox Res 36, 49–57 (2019). https://doi.org/10.1007/s12640-019-00022-0
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DOI: https://doi.org/10.1007/s12640-019-00022-0