Abstract
Rationale: Previous work has indicated that photobiomodulation (PBM), may provide neuroprotection and improve neurological function after acute ischemic stroke. However, the underlying mechanism remains unclear. The present study was performed to examine whether PBM, a noninvasive neurostimulation technique, promotes neurogenesis in a middle cerebral artery occlusion (MCAO) stroke rat model. Methods: Beginning 6 h after MCAO, once-daily 2-min PBM treatments(808 nm) were applied to the infarcted hemisphere for 7 consecutive days. Samples were collected 7 days and 14 days after MCAO stroke. Fluorescent labeling, Western blotting, and behavioral tests were performed accordingly. Results: We found that PBM-treated animals displayed improved motor and sensory functions. PBM treatment significantly expanded the pool of neural progenitor cell (NPC) and newly generated immature neurons in the cortical peri-infarct region after acute ischemic stroke. Application of PBM strikingly diminished the MCAO-induced loss of NPCs and newly-formed neurons. In addition, the amount of newly generated mature neurons in the peri-infarct zone was significantly promoted by PBM treatment. Intriguingly, PBM reduced reactive gliogenesis significantly while promoting oligodendrogenesis and preserving myelination. Mechanistic studies uncovered that PBM enhances the expression of brain-derived neurotrophic factor (BDNF) and initiates the activation of the BDNF/TrkB signaling pathway. Conclusions: Our findings indicate that PBM promotes neurogenesis and functional recovery through stimulating NPC proliferation, reducing NPC and immature neuron cell death, and tamping excessive gliogenesis. These effects were due, in part, to the upregulated release of trophic factors. These findings support PBM as an effective neuroregenerative treatment for acute ischemic stroke. Keywords: Ischemic stroke, Photobiomodulation (PBM), Neurogenesis, Functional recovery, Neurotrophic factors
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