Transcranial direct current stimulation alleviated ischemic stroke induced injury involving the BDNF-TrkB signaling axis in rats.

Ischemic stroke causes a complicated sequence of apoptotic cascades leading to neuronal damage and functional impairments. Transcranial direct current stimulation (tDCS) is a non-invasive treatment technique that uses electrodes to deliver weak current to the head. It could influence brain activity and has a crucial role in neuronal survival and plasticity. The current study investigated the neuroprotective effects and potential mechanisms of tDCS by brain-derived neurotrophic factor (BDNF) and its related receptor tropomyosin-receptor kinase B (TrkB) against apoptosis following ischemic injury in vivo. The effect of consecutive treatment with tDCS for seven days on rats after Middle cerebral artery occlusion/reperfusion (MCAO/R) surgery was studied. Western blotting, immunofluorescent staining, TUNEL assay, and electron microscope were conducted seven days after tDCS treatment, and the motor function was assessed at 1, 3, and 7 days. Activities of BDNF-TrkB signaling axis and apoptosis-related proteins were determined in the cerebral cortex. At seven days after tDCS treatment, it increased BDNF levels and promoted the regeneration of axons compared with the MCAO/R group. There was also a reduction in neuronal apoptosis and improved functional deficits. Whereafter, a TrkB receptor inhibitor K252a was administrated to clarify whether the neuroprotection of tDCS is exerted via BDNF-TrkB signaling. The results depicted that K252a application significantly inhibited the neuroprotection impact of tDCS treatment. It was accompanied by a significant downregulation of phosphorylation of TrkB, PI3K, and Akt. Our study investigated the neuroprotective effects of tDCS against ischemic injury. The results indicate that upregulation of BDNF and its critical receptor TrkB, as well as its downstream PI3K/Akt pathway, were involved in the protective effects exerted by tDCS.