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Neuroprotective Effects of Lycium barbarum Polysaccharide on Focal Cerebral Ischemic Injury in Mice

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Abstract

Increasing evidence demonstrates inflammation contributes to neuronal death following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been reported to prevent scopolamine-induced cognitive and memory deficits. We recently indicated that LBP exerts neuroprotective effect against focal cerebral ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The aim of this study was to investigate the neuroprotective effects of LBP against the behavioral dysfunction induced by focal cerebral ischemia injury in mice. Following 7 successive days of pretreatment with LBP (10, 20 and 40 mg/kg) and nimodipine (4 mg/kg) by intragastric gavage, mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, cerebral blood flows, the total power of the spontaneous EEG, and morphological changes were estimated. Learning and memory ability, and motor coordination were determined by Morris water maze task, rotarod and grip test. Western blot analysis, Real-Time fluorogenic PCR assays, and immunofluorescence staining were used to examine the expression of proinflammatory mediators and activation of microglia. The present study showed that LBP pretreatment significantly enhanced regional cortical blood flow and the total power of the spontaneous EEG, improved memory and motor coordination impairments, and inhibited over-activation of microglia and astrocytes after MCAO. Further study demonstrated LBP suppressed MCAO-induced activations of P65 NF-κB and P38 MAPK, and prevented up-regulations of proinflammatory mediators in hippocampus. Our data suggest that LBP can exert functional recovery of memory and motor coordination deficits and neuroprotective effect against cerebral ischemic injury in mice.

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Abbreviations

DAPI:

4′,6-diamidino-2-phenylindole

ECL:

Enhanced chemiluminescence

H&E:

Hematoxylin and eosin

ICA:

Internal carotid artery

ICR:

Institute of cancer research

IL-1:

Interleukin 1

IL-6:

Interleukin 6

LBP:

Lycium barbarum polysaccharide

LSCI:

Laser speckle contrast imaging

MCA:

Middle cerebral artery

MCAO:

Middle cerebral artery occlusion

MWM:

Morris water maze

Nim:

Nimodipine

NO:

Nitric oxide

rCBF:

Regional cortical blood flow

ROS:

Reactive oxygen species

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

TBST:

Tris-buffered saline/tween-20

TEM:

Transmission electron microscopy

TNF-a:

Tumor necrosis factor-a

TTC:

2,3,5-Triphenyl tetrazolium chloride

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Acknowledgements

The authors gratefully acknowledge the financial support provided by the National Natural Science Foundation of China (Grant No. 81360649).

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    Authors and Affiliations

    1. Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai, 201203, China

      Peng Zhao & Zhong-Ming Qian

    2. Department of Pharmacology, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, Ningxia, China

      Peng Zhao, Ru Zhou, Xiao-Yun Zhu, Gang Liu, Yu-Ping Zhao, Peng-Sheng Ma, Wei Wu & Jian-Qiang Yu

    3. Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China

      Yang Niu

    4. Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 750004, China

      Tao Sun

    5. College of Nursing, Ningxia Medical University, Yinchuan, 750004, China

      Yu-Xiang Li

    6. Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan, 750004, China

      Jian-Qiang Yu

    7. Department of Biochemistry, Institute for Nautical Medicine, Nantong University, Nantong, 226001, China

      Zhong-Ming Qian

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    Correspondence to Jian-Qiang Yu or Zhong-Ming Qian.

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    Peng Zhao and Ru Zhou contributed equally to this study.

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    Zhao, P., Zhou, R., Zhu, XY. et al. Neuroprotective Effects of Lycium barbarum Polysaccharide on Focal Cerebral Ischemic Injury in Mice. Neurochem Res 42, 2798–2813 (2017). https://doi.org/10.1007/s11064-017-2293-x

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