Postischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats

J Cereb Blood Flow Metab. 2004 Nov;24(11):1205-13. doi: 10.1097/01.WCB.0000136525.75839.41.


Fibroblast growth factor (FGF)-2 is a potent neurotrophic and angiogenic peptide. To examine possible protective effects of FGF-2 gene expression against transient focal cerebral ischemia in rats, a replication defective, recombinant adenovirus vector expressing FGF-2, was injected intraventricularly 2 hours after middle cerebral artery occlusion (MCAO). The treatment group showed significant recovery compared with the vehicle-treated groups in terms of serial neurologic severity scores over the 35 days after MCAO. Further, 2,3,5-triphenyltetrazolium chloride staining showed that FGF-2 gene transfer decreased infarct volume by 44% as compared with that in the vehicle-treated groups at 2 days after MCAO. The same tendency of gene transfer effects on infarct volume was confirmed at 35 days after MCAO with hematoxylin/eosin staining. Enzyme-linked immunosorbent assay revealed that FGF-2 concentration was increased significantly at 2 days after MCAO, not only in cerebrospinal fluid but also in cerebral substance in the lesioned and treated animals. These results suggested that FGF-2 gene transfer using these adenoviral vectors might be a useful modality for the treatment of occlusive cerebrovascular disease even after the onset of stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Brain Infarction / complications*
  • Brain Infarction / genetics
  • Brain Infarction / pathology*
  • Brain Infarction / therapy
  • Brain Ischemia / complications*
  • Brain Ischemia / genetics
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / immunology
  • Fibroblast Growth Factor 2 / therapeutic use*
  • Genetic Therapy
  • Genetic Vectors / genetics
  • Immunohistochemistry
  • Injections, Intraventricular
  • Neurons / metabolism
  • Neurons / pathology*
  • Rats
  • Treatment Outcome


  • Fibroblast Growth Factor 2