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Non-invasive remote ischemic postconditioning stimulates neurogenesis during the recovery phase after cerebral ischemia

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Abstract

Ischemic postconditioning (IPostC) has been reported to have neuroprotection against ischemic diseases, and one cycle of IPostC induces neurogenesis when treated nearby. To expanding these effects, we explored the effects of repetitively remote IPostC (NRIPostC) on neurogenesis in the subgranular zone (SGZ) and subentricular zone (SVZ) during stroke recovery. Animals underwent transient cerebral ischemia were treated with vehicle or NRIPostC immediately after reperfusion. Neurological severity scores, infarct size, neurogenesis, and protein expression levels of nestin and GFAP were quantified at 3d, 7d, 14d, 21d and 28d post-ischemia. Results showed that NRIPostC significantly reduced acute infarction and improved neurological outcomes during the recovery phase. Meanwhile, NRIPostC significantly increased the number of BrdU+/nestin+ cells in SGZ on day 14 and in the SVZ on days 3, 7 and 14 respectively, and the number of DCX+ cells from days 3 to 14. There were significant increments in the number of BrdU+/NeuN+ and BrdU+/GFAP+ cells in the SGZ and SVZ during the stroke recovery. The changing tendency of the protein expression of nestin and GFAP in DG was consistent with the result mentioned above. In conclusion, NRIPostC reduced acute infarction and improved functional outcomes up to 28d, and it induced neurogenesis both in the SGZ and SVZ.

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Abbreviations

BrdU:

bromodeoxyuridine

BSA:

bovine serum albumin

DAPI:

4, 6-diamidino-2-phenylindole

DCX:

doublecortex

DG:

dentate gyrus

MCAO:

middle cerebral ischemia

GFAP:

glial fibrillary acidic protein

IPostC:

ischemic postconditioning

I/R:

ischemia/reperfusion

mNSS:

Modified Neurological Severity Score

NeuN:

neuronal nuclear protein

NLIP:

non-invasive limb ischemic postconditioning

rCBF:

regional cerebral blood flow

RIP:

remote ischemic postconditioning

NRIPostC:

non-invasively remote ischemic postconditioning

SGZ:

subgranular zone

SVZ:

subventricular zone

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Acknowledgments

This work was supported by the National Youth Science Foundation (grant number 81401858).

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Authors and Affiliations

  1. Department of Rehabilitation Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Dan Huang, Honghong Liu & Yun Qu

  2. Department of Rehabilitation Medicine, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, People’s Republic of China

    Dan Huang

  3. Department of Rehabilitation Medicine, Ruijin Hospital of Shanghai Jiaotong University School, Shanghai, 200025, People’s Republic of China

    Pu Wang

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  1. Dan Huang
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Correspondence to Yun Qu or Pu Wang.

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Huang, D., Liu, H., Qu, Y. et al. Non-invasive remote ischemic postconditioning stimulates neurogenesis during the recovery phase after cerebral ischemia. Metab Brain Dis 32, 1805–1818 (2017). https://doi.org/10.1007/s11011-017-0068-3

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