title: Enhancement of Neurotrophic Factors in Astrocyte for Neuroprotective Effects in Brain Disorders Using Low-intensity Pulsed Ultrasound Stimulation.
abstract: BACKGROUND
  Astrocytes play an important role in the growth and survival of developing neurons by secreting neurotrophic factors.
  
  
  OBJECTIVE
  The goal of this study was to investigate how low-intensity pulsed ultrasound (LIPUS) stimulation directly affects brain astrocyte function.
  
  
  METHODS
  Here, we report that LIPUS stimulation increased protein levels of BDNF, GDNF, VEGF, and GLUT1 in rat brain astrocytes as measured by western blot analysis. Histological outcomes including demyelination and apoptosis were examined in rats after administration of aluminum chloride (AlCl3).
  
  
  RESULTS
  At the mechanistic level, integrin inhibitor (RGD peptide) attenuated the LIPUS-induced neurotrophic factor expression. The data suggest that neurotrophic factor protein levels may be promoted by LIPUS through activation of integrin receptor signaling. In addition, LIPUS stimulation protected cells against aluminum toxicity as demonstrated by an increase in the median lethal dose for AlCl3 from 3.77 to 6.25 mM. In in vivo histological evaluations, LIPUS significantly reduced cerebral damages in terms of myelin loss and apoptosis induced by AlCl3.
  
  
  CONCLUSIONS
  The results of this study demonstrate that transcranial LIPUS is capable of enhancing the protein levels of neurotrophic factors, which could have neuroprotective effects against neurodegenerative diseases.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: fyyang@ym.edu.tw.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Lu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Lin
authors.affiliation: National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Sin-Luo
authors.initials: SL
authors.lastname: Huang
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D000814:Aniline Compounds; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000378:metabolism*; D052160:Benzothiazoles / Q000493:pharmacokinetics; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D002470:Cell Survival / Q000528:radiation effects; D002712:Chlorides / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000517:prevention & control; D016023:Integrins / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D019636:Neurodegenerative Diseases / Q000517:prevention & control; D020258:Neurotoxicity Syndromes / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles; D014464:Ultrasonic Therapy
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D017607:Aluminum Compounds; D000814:Aniline Compounds; D052160:Benzothiazoles; D002712:Chlorides; D016023:Integrins; D009414:Nerve Growth Factors; D009842:Oligopeptides; D013844:Thiazoles; D000077410:Aluminum Chloride; C047981:arginyl-glycyl-aspartic acid
keywords: Brain disorder; GLUT1; Neuroprotective; Neurotrophic factor; Ultrasound