title: The free radical scavenger, edaravone, ameliorates delayed neuropsychological sequelae after acute carbon monoxide poisoning in rabbits.
abstract: BACKGROUND
  The mechanism underlying delayed neuropsychological sequelae (DNS) after acute carbon monoxide (CO) poisoning is unclear. There are no effective treatments for DNS. As part of a new generation of antioxidants, edaravone has been reported to improve clinical outcomes in patients exhibiting ischemic strokes. There has been little data about edaravone in relationship to DNS prevention and treatment. We hypothesized that edaravone could ameliorate DNS: Here we test that hypothesis in rabbits
  
  
  METHODS
  Rabbits were randomly divided into sham control,DNS group, saline group and edaravone group. DNS model was made by intraperitoneal injection of CO. Normal saline or edaravone (1 mg/kg, twice daily, a total of one course for 14 days) was infused through the ear vein from Day 15 since the DNS model was established. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) were measured in each group. Magnetic resonance spectroscopy (MRS) was used to examine regions of the brain for various compounds. The apoptotic index and neuronal density in the hippocampal CA1 area were also investigated.
  
  
  RESULTS
  SOD activity decreased significantly and MDA content increased substantially in the DNS group and saline group when compared with the sham control (p < 0.01). Conversely, in the edaravone group, serum SOD activity significantly increased and MDA levels significantly decreased when compared with DNS and saline group (p < 0.01). In the DNS group, the spectra of H1-MRS showed an elevated Cho/Cr and Lac/Cr ratio, and a marked decrease in the NAA/Cr ratio (p < 0.01). Compared with the saline group and DNS group, the NAA/Cr ratio was significantly increased, and the Cho/Cr and Lac/Cr ratio were significantly decreased in the edaravone group (p < 0.01). The apoptotic index in the edaravone group was significantly lower than that of the DNS and saline groups (p < 0.01, respectively), while the neuronal density in edaravone group was significantly higher than that of the DNS and saline group in the hippocampal CA1 area (p < 0.01, respectively).
  
  
  CONCLUSIONS
  Our present research demonstrates that edaravone could ameliorate DNS after acute carbon monoxide poisoning in rabbits. These results suggest free radicals could be involved in the underlying mechanisms of DNS. Furthermore, brain MRS shows promise as a tool for early diagnosis for DNS.
authors.affiliation: Department of Neurology, The 105th Hospital of PLA, Clinic College of Anhui Medical University, Hefei, China. wangqs65@yahoo.com
authors.forename: Wang
authors.initials: W
authors.lastname: Qingsong
authors.forename: Guan
authors.initials: G
authors.lastname: Yeming
authors.forename: Liu
authors.initials: L
authors.lastname: Xuechun
authors.forename: Liu
authors.initials: L
authors.lastname: Hongjuan
authors.forename: Wang
authors.initials: W
authors.lastname: Jing
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000097:blood; D002249:Carbon Monoxide Poisoning / Q000097:blood / Q000150:complications* / Q000473:pathology; D002794:Choline / Q000097:blood; D003401:Creatine / Q000097:blood; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D012965:Sodium Chloride / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D016166:Free Radical Scavengers; D001224:Aspartic Acid; D019344:Lactic Acid; D012965:Sodium Chloride; D008315:Malondialdehyde; C000179:N-acetylaspartate; D013482:Superoxide Dismutase; D003401:Creatine; D002794:Choline; D000077553:Edaravone; D000983:Antipyrine