title: Targeting nitric oxide in the subacute restorative treatment of ischemic stroke.
abstract: BACKGROUND
  Stroke remains the leading cause of adult disability. Thus, it is imperative to develop restorative therapies for ischemic stroke designed specifically to treat the intact brain tissue to stimulate functional benefit. Therapies targeting amplification of brain repair processes with nitric oxide (NO) donors and phosphodiesterase type 5 (PDE5) inhibitors in preclinical studies are emerging and showing improvement of functional recovery after stroke.
  
  
  METHODS
  This review will mainly cover the effect of NO donors, which produce NO, and PDE5 inhibitors, which elevate cyclic guanosine 3',5'-monophosphate (cGMP), on neural restorative events in ischemic brain and highlight mechanisms underlying their restorative therapeutic activity.
  
  
  CONCLUSIONS
  During stroke recovery, interwoven restorative events occur in ischemic brain, which include angiogenesis, neurogenesis, oligodendrogenesis, astrogliosis and neurite outgrowth. Emerging preclinical data indicate that restorative therapies targeting multiple parenchymal cells including neural stem cells, cerebral endothelial cells, astrocytes, oligodendrocytes, neurons would be more effective than agents with a single cell target. Preclinical data suggest that elevated cGMP levels induced by NO donors and PDE5 inhibitors act on cerebral endothelial cells, neural stem cells and oligodendrocyte progenitor cells to enhance stroke-induced angiogenesis, neurogenesis and oligodendrogenesis, respectively. These interacting remodeling events collectively improve neurological function after stroke.
authors.affiliation: Henry Ford Hospital, Department of Neurology, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D020030:Nitric Oxide Donors; D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP