title: Edaravone attenuates intracerebroventricular streptozotocin-induced cognitive impairment in rats.
abstract: Alzheimer's disease is a major cause of dementia worldwide. Edaravone, a potent free radical scavenger, is reported to be neuroprotective. The present study was designed to investigate the effect of chronic edaravone administration on intracerebroventricular-streptozotocin (ICV-STZ) induced cognitive impairment in male Wistar rats. Cognitive impairment was developed by single ICV-STZ (3 mg/kg) injection bilaterally on day 1. Edaravone (1, 3 and 10 mg/kg, orally, once daily) was administered for 28 days. Morris water maze and passive avoidance tests were used to assess cognitive functions at baseline and on days 14 and 28. ICV-STZ caused cognitive impairment as evidenced by increased escape latency and decreased time spent in target quadrant in the Morris water maze test and reduced retention latency in the passive avoidance test. STZ caused increase in oxidative stress, cholinesterases, inflammatory cytokines and protein expression of ROCK-II and decrease in protein expression of ChAT. Edaravone ameliorated the STZ-induced cognitive impairment. STZ-induced increase in oxidative stress and increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) were mitigated by edaravone. Edaravone also prevented STZ-induced increased protein expression of ROCK-II. Moreover, edaravone significantly prevented STZ-induced increased activity of cholinesterases in the cortex and hippocampus. The decreased expression of ChAT caused by STZ was brought towards normal by edaravone in the hippocampus. The results thus show that edaravone is protective against STZ-induced cognitive impairment, oxidative stress, cholinergic dysfunction and altered protein expressions. This study thus suggests the potential of edaravone as an adjuvant in the treatment of Alzheimer's disease.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: K H
authors.identifier: 0000-0002-3824-5498
authors.initials: KH
authors.lastname: Reeta
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Devendra
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Yogendra K
authors.initials: YK
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002802:Cholinesterases / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D011950:Receptors, Cholinergic / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D011950:Receptors, Cholinergic; D013311:Streptozocin; D054460:rho-Associated Kinases; D002802:Cholinesterases; D000077553:Edaravone; D000983:Antipyrine
keywords: 
  ROCK II
  ; choline acetyltransferase; cholinesterases; edaravone; oxidative stress