Both brain-derived neurotrophic factor (BDNF) and microglia activation are involved in the pathogenesis of ischemic stroke. Herein, we attempt to ascertain whether Calycosin, an isoflavonoid, protects against ischemic stroke by modulating the endogenous production of BDNF and/or the microglia activation. This study was a prospective, randomized, blinded and placebo-controlled preclinical experiment. Sprague-Dawley adult rats, subjected to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO), were treated randomly with 0 (corn oil and/or saline as placebo), 30 mg/kg of Calycosin and/or 1 mg/kg of a tropomyosin-related kinase B (TrkB) receptor antagonist (ANA12) at 1 h after reperfusion and once daily for a total of 7 consecutive days. BDNF and its functional receptor, full-length TrkB (TrkB-FL) levels, the percentage of hypertrophic microglia, tumor necrosis factor-α (TNF-α)-containing microglia, and degenerative and apoptotic neurons in ischemic brain regions were determined 7 days after cerebral ischemia. A battery of functional sensorimotor test was performed over 7 days. Post-stroke Calycosin therapy increased the cerebral expression of BDNF/TrkB, ameliorated the neurological injury and switched the microglia from the activated amoeboid state to the resting ramified state in ischemic stroke rats. However, the beneficial effects of BDNF/ TrkB-mediated Calycosin could be reversed by ANA12. Our data indicate that BDNF/TrkB-mediated Calycosin ameliorates rat ischemic stroke injury by switching the microglia from the activated amoeboid state to the resting ramified state.
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brain-derived neurotrophic factor
cerebral blood flow
corrected infarction volume
- d :
thickness of the brain slices
external carotid artery
enzyme-linked immunosorbent assay
ionized calcium binding adaptor molecule 1
internal carotid artery
middle cerebral artery occlusion
modified neurological severity score
right side infarct
tumor necrosis factor-alpha
full-length tyrosine kinase receptor B
2,3,5-triphenyl tetrazolium chloride
terminal deoxynucleotidyl transferase dUTP nick end labeling
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The authors would like to thank Ms. Meng-Tsung Ho for her excellent editorial assistance in manuscript preparation.
This work was supported by grants from the Ministry of Science and Technology (Taiwan) (MOST 107-2314-B-384-004) and Chi Mei Medical Center (Tainan, Taiwan) (CMFHT10504).
Ethics Approval and Consent to Participate
All animal research was ethically approved by the Institutional Animal Care and Use Committee of Chi Mei Medical Center (IACUC approved no. 105110328). Experiments adhered to guidelines from the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
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Hsu, C., Kuo, T., Liu, W. et al. Calycosin Preserves BDNF/TrkB Signaling and Reduces Post-Stroke Neurological Injury after Cerebral Ischemia by Reducing Accumulation of Hypertrophic and TNF-α-Containing Microglia in Rats. J Neuroimmune Pharmacol (2020) doi:10.1007/s11481-019-09903-9
- Brain-derived neurotrophic factor
- Neuronal death