Neuroprotective effect of a heat shock protein inducer, geranylgeranylacetone in permanent focal cerebral ischemia.
Previous studies have strongly suggested that heat shock protein 70 (HSP70) has protective effects in ischemia/reperfusion in tissues such as brain, heart, and liver. This study was performed to assess the efficacy of the HSP70 inducer geranylgeranylacetone (GGA) in experiments involving permanent middle cerebral artery (MCA) occlusion. Male Balb/c mice were subjected to permanent MCA occlusion by direct occlusion through small craniectomy. Vehicle or GGA (200 or 1000 mg/kg) was injected intraperitoneally 1 h prior to the onset of ischemia. Infarct volumes were evaluated at 24 h of ischemia by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. The effect of GGA on the induction of HSP70 was studied at 3 h after ischemia with fluorescence immunocytochemistry. The percentage of infarct volume in the control mice (n=10) was 23.0+/-4.0% (mean+/-SD) of the contralateral hemisphere, while those in the treated groups were 22.6+/-7.3% (200 mg/kg group; n=5, P>0.05) and 15.7+/-3.8% (1000 mg/kg group; n=5, P<0.05). Pretreatments with 1000 mg/kg of GGA enhanced the ischemia-related induction of HSP in the neurons and astrocytes in the boundary zone of infarct. The results demonstrate that GGA significantly reduces infarct volume due to permanent MCA occlusion when given 1 h prior to the induction of ischemia.
Yasuda
Hiroshi
H
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.
Shichinohe
Hideo
H
Kuroda
Satoshi
S
Ishikawa
Tatsuya
T
Iwasaki
Yoshinobu
Y
D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013778:Tetrazolium Salts
D004224:Diterpenes; D005904:Glial Fibrillary Acidic Protein; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; C031049:geranylgeranylacetone