Gene transfer of PEDF attenuates ischemic brain damage in the rat middle cerebral artery occlusion model.
Pigment epithelium-derived factor (PEDF) is a 50-kDa glycoprotein that protects various types of cultured neurons against neurotoxic stimuli, but its precise role in the CNS is not fully understood. In this study, we used rats whose brains were transfected to over-express human PEDF in order to elucidate the neuroprotective effect of PEDF following transient middle cerebral artery occlusion (MCAO). A replication-defective adenoviral vector containing the human PEDF gene (Ad.PEDF) or E. colibeta-galactosidase (Ad.LacZ) was directly injected into the right striatum at 7 days prior to 70 min of MCAO in rats. Infarct volume and degree of edema of the Ad.PEDF-treated group were significantly reduced compared to the Ad.LacZ-treated group 24 h after MCAO. Degeneration of neurons, astrocytes, and oligodendrocytes caused by MCAO were attenuated by over-expression of PEDF. The up-regulation of pro-inflammatory genes (TNFalpha, IL-1beta, IL-6, COX-2, and iNOS) and water channel aquaporin 4 after MCAO was significantly reduced in Ad.PEDF-injected striatum. In conclusion, the results from this study provide the first in vivo evidence that PEDF is effective in protecting CNS neurons from ischemic insult, suggesting that PEDF may have a role as an endogenous neuroprotectant in the CNS.
Sanagi
Tomomi
T
Kitasato Institute for Life Sciences, Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
Yabe
Takeshi
T
Yamada
Haruki
H
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000096:biosynthesis / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000627:therapeutic use; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor