Stereo-selective neuroprotection against stroke with vitamin A derivatives.
In this study we evaluated the neuroprotective potential of vitamin A (all-trans retinol), and its geometric isomers, all-trans retinoic acid and 9-cis retinoic acid, in a focal model of ischemia. A 60 minute middle cerebral artery occlusion in C57 mice resulted in over 50% hemispheric infarction. Vitamin A (retinol) and its derivatives were administered as two i.p. injections immediately prior to and following ischemia. A reduction in infarct volume was observed with all-trans retinol, in a dose-dependent manner: maximum protection was observed with a 10 mg/kg dose. A similar protective profile was observed with all-trans retinol, but not the stereo-isomer 9-cis retinoic acid. Administration of the derivatives 1 h following ischemia did not produce significant protection. Taken together these data suggest a possible use of vitamin A derivatives as an acute neuroprotective strategy for stroke.
Sato
Yu
Y
Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon, USA.
Meller
Robert
R
Yang
Tao
T
Taki
Waro
W
Simon
Roger P
RP
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007202:Indicators and Reagents; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013237:Stereoisomerism; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013778:Tetrazolium Salts; D016896:Treatment Outcome; D014801:Vitamin A / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use
D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D014815:Vitamins; D014801:Vitamin A