1-3-dihydroxy-4-4-5-5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole and Cerebral-Infarction

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.. 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.. 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).. 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.

Topics: Animals; Benzoates; Brain Ischemia; Cerebral Infarction; Imidazoles; Male; Neuroprotective Agents; Nitric Oxide; Rats; Rats, Sprague-Dawley