Neuroprotective properties of the non-peptidyl radical scavenger IAC in rats following transient focal cerebral ischemia.
Experimental evidence suggests that reactive free radicals are generated during brain ischemia. We investigated the effect of a novel brain penetrant, low molecular weight, non-peptidyl carbon, oxygen- and nitrogen-centered radical scavenger, IAC, on infarct volume and sensory-motor performance in a rat transient middle cerebral artery occlusion model (tMCAO). Rats received 90 min tMCAO and treated with i.p. or i.v. injections of vehicle or IAC following tMCAO. Sensory-motor performance was evaluated by neuroscore tests (NS). Cerebral infarct volume was evaluated at 72 h after tMCAO. Rats treated with IAC i.p. (1 or 6 h after the onset of tMCAO) or i.v. (1 h after the onset of tMCAO) showed significant improvement in NS during the 3 or 21 day follow-up period when compared to vehicle treated rats. Cerebral infarct volumes were significantly decreased compared to vehicle in rats receiving IAC i.p. 1 h or 6 h after occlusion, approximately 30.5% decrease compared to vehicle, or i.v. 1 h after the onset of tMCAO, 48.6% decrease compared to vehicle. These results demonstrate that IAC has neuroprotective properties with a wide therapeutic window following tMCAO in rats. IAC could therefore be a candidate for the treatment of stroke.
Nurmi
Antti
A
Cerebricon Ltd, Finland.
Miettinen
Taina-Kaisa
TK
Puoliväli
Jukka
J
Pussinen
Raimo
R
Soleti
Antonio
A
Bagate
Karim
K
Riccardino
Francesca
F
Grundy
Robert I
RI
Yrjänheikki
Juha
J
Canistro
Donatella
D
Paolini
Moreno
M
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
D004952:Esters; D018696:Neuroprotective Agents; D010880:Piperidines; C526136:bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate