Neuroprotective effect of geranylgeranylacetone, a noninvasive heat shock protein inducer, on cerebral infarction in rats.
The present study evaluated the neuroprotective effect of geranylgeranylacetone (GGA), which is known as an antiulcer agent and more recently as a heat shock protein (HSP) inducer, against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion. GGA was given orally in various regimens prior to MCA occlusion in rats. Pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia significantly attenuated cerebral infarction volume (81.7+/-18.4 mm3 versus 369.1+/-70.2 mm3; P<.01). A significant increase in HSP70 immunoreactivity was found in the neocortex in GGA-treated animals with or without ischemia. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against cerebral ischemic neuronal damage.
Nagai
Yasuyuki
Y
Department of Neurosurgery, School of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Oita 879-5593, Japan.
Fujiki
Minoru
M
Inoue
Ryo
R
Uchida
Susumu
S
Abe
Tatsuya
T
Kobayashi
Hidenori
H
Cetinalp
Nuri Eralp
NE
D000818:Animals; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004224:Diterpenes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D013778:Tetrazolium Salts; D013997:Time Factors
D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; C031049:geranylgeranylacetone