Extracorporeal shock wave therapy effectively protects brain against chronic cerebral hypo-perfusion-induced neuropathological changes

Han Tan Chai, Kuan Hung Chen, Christopher Glenn Wallace, Chih Hung Chen, Pei Hsun Sung, Yung Lung Chen, Chun Man Yuen, Pei Lin Shao, Cheuk Kwan Sun, Hsueh Wen Chang, Ching Jen Wang, Mel S. Lee, Hon Kan Yip*, Sheung Fat Ko

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations

Abstract

This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy could protect mouse brain from chronic cerebral hypoperfusion (CHP)-induced neuropathological changes in a bilateral carotid arterial stenosis (CAS) model. Adult-male C57BL/6 (B6) mice (n=36) were randomized into group 1 (sham-control), group 2 (CHP) and group 3 [CHP+ECSW (100 impulses at 0.15 mJ/mm2) on day 5, 10 and 15 after CHP induction]. By day 60 after CHP induction, the white matter lesion, protein expressions of inflammatory (TNF-α/NF-κB/iNOS), oxidative-stress (NOX-1/NOX-2/NOX-4/nitrotyrosine), angiogenesis (eNOS/CD31), apoptotic (Bax/caspase-3/PARP), fibrotic (Smad3/TGF-ß) and mitochondrial-damaged (cytosolic cytochrome-C) biomarkers were significantly higher in group 2 than in groups 1 and 3, and significantly higher in group 3 than in group 1, whereas the protein expressions of antiapoptotic (Bcl-2), anti-fibrotic (BMP-2/Smad1/5), and mitochondrial-integrity (mitochondrial cytochrome-C) biomarkers showed an opposite pattern to inflammation among the three groups (all P<0.0001). The cellular expressions of inflammatory (Iba-1/GFAP/CD14, F4/80), apoptotic (TUNEL-assay) and brain-damaged (γ-H2AX/AQP4) biomarkers showed an identical pattern to inflammation, whereas the cellular expressions of endothelial-cell (CD31/vWF), neu-ron/energy-integrity (NeuN/PGC-1α) and small-vessel density exhibited an opposite pattern to inflammation among the three groups (all P<0.0001). Cellular angiogenesis (VEGF/SDF-1α) significantly and progressively increased from groups 1 to 3 (all P<0.0001). In conclusion, ECSW therapy enhanced angiogenesis, inhibited molecular-cellular perturbations, and protected the white matter and neuron from CHP damage.

Original languageEnglish
Article numberAJTR0055857
Pages (from-to)5074-5093
Number of pages20
JournalAmerican Journal of Translational Research
Volume9
Issue number11
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2017, E-Century Publishing Corporation. All rights reserved.

Keywords

  • Angiogenesis
  • Apoptosis
  • Chronic cerebral hypoperfusion
  • Extracorporeal shock wave therapy
  • Inflammation
  • Oxidative stress

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