TY - JOUR
T1 - Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells
AU - Yang, Luodan
AU - Tucker, Donovan
AU - Dong, Yan
AU - Wu, Chongyun
AU - Lu, Yujiao
AU - Li, Yong
AU - Zhang, Juan
AU - Liu, Timon Cheng Yi
AU - Zhang, Quanguang
N1 - Funding Information:
This study was supported by Research Grant NS086929 from the National Institute of Neurological Disorders and Stroke , National Institutes of Health , USA; an American Heart Association Grant-in-Aid 15GRNT25240004 , and National Natural Science Foundation of China : 61575065 & 11604104 .
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1
Y1 - 2018/1
N2 - Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808 nm, 350 mW/cm2, total 294 J at scalp level) was applied on the infarct injury area (1.8 mm anterior to the bregma and 2.5 mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50 mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.
AB - Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808 nm, 350 mW/cm2, total 294 J at scalp level) was applied on the infarct injury area (1.8 mm anterior to the bregma and 2.5 mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50 mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.
KW - Inflammation
KW - Ischemic stroke
KW - Mitochondrial function
KW - Neurogenesis
KW - Photobiomodulation
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U2 - 10.1016/j.expneurol.2017.10.013
DO - 10.1016/j.expneurol.2017.10.013
M3 - Article
C2 - 29056360
AN - SCOPUS:85032214253
SN - 0014-4886
VL - 299
SP - 86
EP - 96
JO - Experimental Neurology
JF - Experimental Neurology
ER -