Chinese Medical Sciences Journal ›› 2017, Vol. 32 ›› Issue (2): 92-99.doi: 10.24920/J1001-9294.2017.020

• Original Article • Previous Articles     Next Articles

Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion Brain Injury

Kong Xiangyi1, 2, Guan Jian1, Gong Shun3, 4, Wang Renzhi1, *()   

  1. 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
    2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, Massachusetts 02114, USA
    3Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
    4Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Massachusetts 02215, USA
  • Received:2017-02-17 Online:2017-06-20 Published:2017-06-10
  • Contact: Wang Renzhi E-mail:wrzpumch@163.com
  • Supported by:
    △Supported by Peking Union Medical College Youth Research Funds (3332016010) and Peking Union Medical College Graduate Student Innovation Fund (2015-1002-02-09).

Abstract:

Objective Oxidative stress (OS) plays a crucial role in ischemic stroke. Grape seed procyanidin extract (GSPE) was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in ischemia-reperfusion brain injury. This study aimed to explore whether GSPE administration can protect mice from ischemia-reperfusion brain injury.Methods Transient middle cerebral artery occlusion (MCAO) was conducted followed by reperfusion for 24 hours to make ischemia-reperfusion brain injury in mice that received GSPE (MCAOG, n=60) or normal saline (MCAONS, n=60). Sham-operated mice (GSPE group and normal saline group) were set as controls. The neurological severity score (NSS) was used to evaluate neural function impairment 1 hour, 24 hour, 3 days and 7 days after MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours after reperfusion, and the stroke volume of brains were calculated according to abnormal signal intensity. Immunohistopathological analysis of brain tissues at 24 h after reperfusion was performed for neuronal nuclear antigen (NeuN), CD34, Bcl-2, and Bax. Glutathione peroxidation (GSH-Px) activity and the level of malonaldehyde (MDA) of brain tissue were also examined. The above indexes were compared among the groups statistically.Results Significant functional improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS group (P<0.05). MCAOG group had smaller cerebral stroke volume (22.46 ± 11.45 mm3 vs. 47.84±9.06 mm3, P<0.05) than MCAONS group 24 hours after MCAO. More mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of MCAONS mice (both P<0.05). MCAONS mice had significantly higher number of Bax-positive cells in brain tissue than MCAOG (P<0.05). The mean MDA level was significantly lower (P<0.05) and the GSH-Px activity was significantly higher (P<0.05) in brains of MCAOG mice compared to those of MCAONS mice.Conclusion GSPE administration protects mice from ischemia-reperfusion brain injury through attenuating oxidative stress and apoptosis, promoting angiogenesis, and activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical direction for the treatment of ischemia-reperfusion brain injury.

Key words: grape seed procyanidin extract, oxidative stress, neuroprotection, ischemia-reperfusion injury

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