title: Nerve growth factor-carbon nanotube complex exerts prolonged protective effects in an in vitro model of ischemic stroke.
abstract: OBJECTIVE
  The therapeutic potential of nerve growth factor (NGF) against the neurological disorders may be negatively affected by its short half-life. Based on the superior properties of carbon nanotubes (CNTs) for controlled drug delivery, we aimed to prepare CNT-NGF complex and evaluate its effect in an in vitro model of ischemic stroke.
  
  
  METHODS
  Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the absence or presence of NGF (0.5, 1, 2μg/ml), acid- or amine-modified MWCNTs, or MWCNTs-NGF complex (2, 4, 8μg/ml) were exposed to 1 and 6h oxygen-glucose deprivation (OGD) followed by 24h re-oxygenation. Cytotoxicity and oxidative stress were evaluated.
  
  
  RESULTS
  OGD significantly reduced the cell viability (P<0.001). NGF dose-dependently increased the cell viability only after 1-h OGD (P<0.05), while, MWCNTs-NGF complex was effective at both 1- and 6-h OGD (P<0.05, P<0.001). NGF reduced the formation of condensed nuclei due to 1-h OGD (P<0.01, P<0.001), while, MWCNTs-NGF showed efficiency at both time points (P<0.05, P<0.01, P<0.001). OGD significantly increased malondialdehyde (MDA) content and decreased catalase (CAT) and superoxide dismutase (SOD) activities (P<0.001). After 1-h OGD, NGF reduced MDA (P<0.001) and increased CAT (P<0.05, P<0.01) and SOD (P<0.01), while, MWCNTs-NGF was effective after both 1- and 6-h OGD (MDA: P<0.01, P<0.001, CAT: P<0.001, SOD: P<0.01, P<0.001).
  
  
  CONCLUSIONS
  Aminated MWCNTs-NGF complex by providing longer lasting effects for NGF might be of therapeutic significance against the disorders associated with NGF deficiency.
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Neurological Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: p-hassanzadeh@razi.tums.ac.ir.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Hassanzadeh
authors.affiliation: Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: arbabiavalelham@gmail.com.
authors.forename: Elham
authors.initials: E
authors.lastname: Arbabi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Dinarvand@tums.ac.ir.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D020521:Stroke / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D037742:Nanotubes, Carbon; D008315:Malondialdehyde; D020932:Nerve Growth Factor; D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose; D010100:Oxygen
keywords: Carbon nanotubes; Ischemic stroke; NGF; Oxidative stress