Fructose-1,6-bisphosphate after hypoxic ischemic injury is protective to the neonatal rat brain.
Fructose-1,6-bisphosphate (FBP) has been shown to attenuate central nervous system injury in adult animals. We evaluated whether FBP given after an ischemic-hypoxic insult is protective to the developing brain in a neonatal rat model of hypoxia-ischemia. Postnatal day 7 rat pups were subjected to focal ischemia followed by global hypoxia and then administered either FBP or saline intraperitoneally. A dose of 500 mg/kg or greater of FBP significantly reduced the amount of injury such that 55% of FBP- vs. 17% of saline-treated rats had no injury; 6% of FBP- and 47% of saline-treated rats had severe damage (P = 0.004). There was less infarcted brain in FBP-treated rats (12 +/- 11% vs. 37 +/- 32%; P = 0.005); and fewer FBP-treated rats had > 30% ipsilateral cortical injury (12% of FBP- vs. 50% of saline-treated rats; P = 0.002). FBP lowered serum calcium levels during the first 24 h after the insult without significant changes in ionized calcium or osmolarity. These results indicate that FBP treatment administered systemically after hypoxia-ischemia reduces CNS injury in neonatal rats.
Sola
A
A
Department of Pediatrics (Neonatology), University of California, San Francisco 94143-0734, USA. asola@peds.ucsf.edu
Berrios
M
M
Sheldon
R A
RA
Ferriero
D M
DM
Gregory
G A
GA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001774:Blood Chemical Analysis; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002544:Cerebral Infarction / Q000473:pathology; D005635:Fructosediphosphates / Q000627:therapeutic use*; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D010758:Phosphorus; C029063:fructose-1,6-diphosphate; D002118:Calcium