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Combination Therapy with LXW7 and Ceria Nanoparticles Protects against Acute Cerebral Ischemia/Reperfusion Injury in Rats

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Abstract

Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra, which results in brain damage. Integrin αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion. We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle (CeNP) (bLXW7-CeNP) plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than CeNPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively. Male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h reperfusion. Drug treatment was intravenously administered via the caudal vein 1 h after occlusion. Rats were randomly divided into the following 4 groups: bLXW7-CeNP treatment group (0.5 mg/kg); CeNP treatment group (0.5 mg/kg); control saline group; and sham group. Brains were harvested 24 h after reperfusion, and the neurologic deficit scores, infarction volume, blood-brain barrier (BBB) disruption, and the level of oxidative stress and apoptosis were determined. Results showed that the bLXW7-CeNP and CeNP treatments could improve neurologic deficit scores, infarction volume, BBB disruption, and the level of oxidative stress and apoptosis. Compound bLXW7-CeNP treatment exhibited better effects than CeNp treatment and showed remarkable statistical differences in the infarction volume, the degree of BBB breakdown, the apoptosis and oxidative stress, apart from neurologic deficit scores. Thus, we concluded that bLXW7-CeNP protects against acute cerebral ischemia/reperfusion injury. BLXW7, as a ligand of integrin αvβ3, may be able to effectively localize the anti-oxidant CeNPs to the ischemic penumbra region, which may provide more adequate opportunities for CeNPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.

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Authors and Affiliations

  1. Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, 518000, China

    Ting Zhang  (张 婷), Jing-jing Jia  (贾静静), Jie-shan Chi  (池洁珊), Jian-zhou Li  (李鉴洲), Xiao-ma Liu  (刘小马) & Li Yi  (易 黎)

  2. College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, China

    Chang-yan Li  (李常艳) & Jun Zhang  (张 军)

  3. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China

    Da Zhou  (周 达)

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  1. Ting Zhang  (张 婷)
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  2. Chang-yan Li  (李常艳)
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Correspondence to Li Yi  (易 黎).

Additional information

This work was supported by grants from Shenzhen Science and Technology Innovation Committee (No. JCYJ20140415162543033), Startup Fund Project of Inner Mongolia University (No. 21300-5145152), Key Project of Education Department of Inner Mongolia (No. NJZZ16015), and the Natural Science Foundation of Inner Mongolia (No. 2016MS0216).

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Zhang, T., Li, Cy., Jia, Jj. et al. Combination Therapy with LXW7 and Ceria Nanoparticles Protects against Acute Cerebral Ischemia/Reperfusion Injury in Rats. CURR MED SCI 38, 144–152 (2018). https://doi.org/10.1007/s11596-018-1858-5

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  • DOI: https://doi.org/10.1007/s11596-018-1858-5

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