Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat.
Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 +/- 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 +/- 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.
Department of Pediatrics, University of Mississippi Medical Center, USA.
Yangzheng
Y
Feng
Ian A
IA
Paul
Michael H
MH
LeBlanc
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001284:Atrophy / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D016893:Carotid Stenosis / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009536:Niacinamide / Q000494:pharmacology* / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use
D014803:Vitamin B Complex; D009536:Niacinamide; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases