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A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat

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Abstract

Remote ischemic perconditioning (RIPerC) and ischemic postconditioning (IPOC) are well-acknowledged neuroprotective procedures during ischemic injury. The present study established a combined RIPerC and IPOC (RIPerC + IPOC) model in rats and studied how it would regulate the autophagy process and affect HMGB1 levels in a rat model of middle cerebral artery occlusion (MCAO). Rats with MCAO were treated with RIPerC by fastening and release of the left hind limb to achieve 4 cycles of 5 min remote ischemia reperfusion, 40 min prior to cerebral reperfusion, and then treated with IPOC by exposing the cerebral middle artery to 3 cycles of 30 s reperfusion/30 s occlusion at the onset of cerebral reperfusion. Infarction volumes, neurological deficits, and pathological changes were assessed 24 h after ischemia. The autophagy activator rapamycin (RAP) and the autophagy inhibitor 3-methyladenine (3-MA) were administrated for further mechanism. The expression and location of HMGB1 and the autophagy-related proteins like LC3, Beclin1, and P62 as well as plasma HMGB1 levels were measured. Our results suggested that RIPerC + IPOC attenuated plasma HMGB1 levels to intensify its neuroprotective effect against cerebral ischemic reperfusion injury via inhibiting the autophagy process.

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Abbreviations

I/R:

Ischemia reperfusion

IPOC:

Ischemic postconditioning

RIPerC:

Remote ischemic perconditioning

MCA:

Middle cerebral artery

MCAO:

Middle cerebral artery occlusion

HMGB1:

High-mobility group box 1

RAP:

Rapamycin

3-MA:

3-Methyladenine

MNSS:

Modified neurological severity scores

TTC:

2,3,5

Triphenyltetrazolium chloride

TEM:

Transmission electron microscopy

FJC:

Fluoro-Jade C

i.c.v.:

Intracerebral ventricle injection

GFAP:

Glial fibrillary acidic protein

IDV:

Integrated density value

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Acknowledgments

This study was partially supported by a grant from the Liaoning Province Science and Technology Project—Animal Scientific Research and Clinical Application for Major Disease of Liaoning Province (2012225021) and Science and Technology Projects of Liaoning Province (2009225010-2) to Dr. Feng.

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Authors and Affiliations

  1. Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, No.36 Sanhao Street, Shenyang, 110004, China

    Jue Wang, Dong Han, Miao Sun & Juan Feng

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  1. Jue Wang
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  2. Dong Han
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  3. Miao Sun
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  4. Juan Feng
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Correspondence to Juan Feng.

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Wang, J., Han, D., Sun, M. et al. A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat. J Mol Neurosci 58, 424–431 (2016). https://doi.org/10.1007/s12031-016-0724-9

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  • DOI: https://doi.org/10.1007/s12031-016-0724-9

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