Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells

Luodan Yang, Donovan Tucker, Yan Dong, Chongyun Wu, Yujiao Lu, Yong Li, Juan Zhang, Timon Cheng Yi Liu, Quanguang Zhang

Research output: Contribution to journalArticle

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Abstract

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/cm 2 , 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.

Original languageEnglish (US)
Pages (from-to)86-96
Number of pages11
JournalExperimental Neurology
Volume299
DOIs
StatePublished - Jan 1 2018

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Neurogenesis
Stroke
Bromodeoxyuridine
Anti-Inflammatory Agents
Cytokines
Phenotype
Synaptophysin
Gliosis
Therapeutic Uses
Electron Transport Complex IV
Nervous System Diseases
Intraperitoneal Injections
Scalp
Adenosine Triphosphate
Low-Level Light Therapy
Wounds and Injuries
Therapeutics

Keywords

  • Inflammation
  • Ischemic stroke
  • Mitochondrial function
  • Neurogenesis
  • Photobiomodulation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells. / Yang, Luodan; Tucker, Donovan; Dong, Yan; Wu, Chongyun; Lu, Yujiao; Li, Yong; Zhang, Juan; Liu, Timon Cheng Yi; Zhang, Quanguang.

In: Experimental Neurology, Vol. 299, 01.01.2018, p. 86-96.

Research output: Contribution to journalArticle

Yang, Luodan ; Tucker, Donovan ; Dong, Yan ; Wu, Chongyun ; Lu, Yujiao ; Li, Yong ; Zhang, Juan ; Liu, Timon Cheng Yi ; Zhang, Quanguang. / Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells. In: Experimental Neurology. 2018 ; Vol. 299. pp. 86-96.
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