Neuroprotective effects of sodium orthovanadate after hypoxic-ischemic brain injury in neonatal rats.
Sodium orthovanadate (SOV), a competitive inhibitor of protein tyrosine phosphatases, is neuroprotective in adult animals following an ischemic event. The present study evaluated whether SOV might be protective in a rat pup hypoxic-ischemic (HI) model. Seven-day-old rat pups had the right carotid artery permanently ligated followed by 140 min of hypoxia (8% oxygen). SOV 1.15, 2.3, 4.6, 9.2 or 18.4 mg/kg and vehicle were administered by i.p. injection at 5 min after reoxygenation. Brain damage was evaluated by weight loss of the right hemisphere at 22 days after hypoxia and by gross and microscopic morphology. SOV lowered blood glucose at doses of 1.15, 2.3 and 4.6 mg/kg and induced toxic effects at 9.2mg/kg. The doses of 2.3 and 4.6 mg/kg of SOV significantly reduced brain weight loss (p<0.05), but treatment with 1.15 or 9.2mg/kg did not. SOV 4.6 mg/kg also improved the histopathologic score and diminished the HI induced reduction of Akt and ERK-1/2 phosphorylation in the cortex (p<0.05) and increased the density of BrdU-positive cells in the subventricular zone (p<0.01). In conclusion, SOV has neuroprotective effects in the neonatal rat HI model partially mediated by activating Akt and ERK-1/2 pathways.
Feng
Yangzheng
Y
Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA. yfeng@ped.umsmed.edu
Bhatt
Abhay J
AJ
Fratkin
Jonathan D
JD
Rhodes
Philip G
PG
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000378:metabolism*
D001786:Blood Glucose; D018696:Neuroprotective Agents; D014638:Vanadates; D048049:Extracellular Signal-Regulated MAP Kinases