Growth inhibitory factor (GIF) can protect from brain damage due to stab wounds in rat brain.
We examined the effect of growth inhibitory factor (GIF), also called metallothionein-III (MT-III), in brain damage using a stab wound model. The administration of 3 microM purified rat GIF (prGIF) provided significantly improved brain repair compared with controls, whereas the administration of 15 microM prGIF reduced brain repair compared with controls. To maintain the continuous effect of GIF, we generated an adenoviral vector encoding rat GIF and the myc epitope (AxCArGIFM) and administered an appropriate amount (1 x 10(8) pfu) of AxCArGIFM on the basis of the optimal dosage determined in a previous study on avulsion of the facial nerve. The administration of AxCArGIFM provided significantly improved histological and biochemical parameters of brain repair compared with controls administered AxCALacZ (adenovirus encoding bacterial beta-galactosidase gene as a reporter; 1 x 10(8) pfu). These results show that GIF can protect from brain damage in certain appropriate conditions in vivo and in vitro. The optimal dosage is very important for the treatment in vivo, particularly that for GIF. Our findings show the double-edged effects of GIF. MTs including MT-III are promising as therapeutic agents not only for tissue repair following acute brain injury, but also for some neurodegenerative diseases because they have multifunctional potential including anti-oxidation effects and may have some effect on neurogenesis.
Hozumi
Isao
I
Department of Neurology and Geriatrics, Gifu University, Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan. ihozumi@cc.gifu-u.ac.jp
Uchida
Yoko
Y
Watabe
Kazuhiko
K
Sakamoto
Tsuyoshi
T
Inuzuka
Takashi
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000473:pathology*; D000939:Epitopes / Q000235:genetics; D005154:Facial Nerve / Q000473:pathology; D019922:GAP-43 Protein / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D008297:Male; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000627:therapeutic use*; D018696:Neuroprotective Agents; D051381:Rats; D017208:Rats, Wistar; D014951:Wounds, Stab / Q000473:pathology*; D001616:beta-Galactosidase / Q000235:genetics
D000939:Epitopes; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D001616:beta-Galactosidase