Nitric oxide scavenger carboxy-PTIO reduces infarct volume following permanent focal ischemia.
BACKGROUND
Nitric oxide (NO) has been shown to play a dual role as a neuroprotectant and a neurotoxin in cerebral ischemia. Free radical scavengers protect brain tissue from ischemic injury. Consequently, we examined the neuroprotective action of NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), in cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO) in rats and mice.


METHODS
All experiments were performed in a randomized fashion. In the first series of experiments, adult Sprague-Dawley rats (n = 31) subjected to permanent MCAO were treated with carboxy-PTIO (0.3, 0.6 mg/kg) or vehicle (normal saline) injected intraperitoneally (IP) 1 hr before permanent MCAO. In the second series of experiments, adult C57BL/6NCrj mice (n = 49) were treated with carboxy-PTIO (0.6, 1.2 mg/kg) or vehicle saline 30 min following MCAO. Neurobehavioral scores were determined 22-24 hr following permanent MCAO and infarct volumes determined by quantitative image analysis of 2, 3, 5-triphenyltetrazolium (TTC)-stained brain sections.


RESULTS
Pre-treatment with carboxy-PTIO at 0.6 mg/kg IP in rats significantly attenuated infarct volume (19.9 +/- 2.9%; n = 10) as compared with vehicle-treated controls (29.2 +/- 2.7%; n = 16), but not at 0.3 mg/kg (28.3 +/- 8.4%; n = 5). Post-MCAO treatment in mice with 0.6 mg/kg carboxy-PTIO (30.3 +/- 3.9%; n = 16) significantly attenuated infarct volume as compared with vehicle-treated controls (46.1 +/- 2.8%; n = 18).


CONCLUSIONS
These data demonstrate that NO scavenger, carboxy-PTIO, provides significant ischemic neuroprotection when given as a pre-treatment as well as after the onset of permanent focal ischemia in two animal species.
Fang
Shih-Yuan
SY
Neurophysiology Laboratory, Anesthesiology & Neurosurgery, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan, ROC.
Tseng
Chia-Chih
CC
Yang
Yao-Lin
YL
Lee
E-Jian
EJ
Chen
Hung-Yi
HY
Bhardwaj
Anish
A
Chen
Tsung-Ying
TY
D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D002544:Cerebral Infarction / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001565:Benzoates; D007093:Imidazoles; D018696:Neuroprotective Agents; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide