Long-term functional and protective actions of preconditioning with hypoxia, cobalt chloride, and desferrioxamine against hypoxic-ischemic injury in neonatal rats.
Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride (CoCl2) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury in neonatal rat brain. We examined long-term functional and protective actions of preconditioning induced by hypoxia, CoCl(2) and DFX in a neonatal rat model of HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8% oxygen) or injections of CoCl(2), DFX or saline vehicle and 24 h later rats underwent HI or sham surgery. Behavioral tests were performed and at the conclusion of experiments, brains removed for morphologic analyses. HI resulted in a large unilateral lesion in the ipsilateral hemisphere compared with sham control rats. All preconditioning treatments significantly reduced the total lesion volume. Behavioral deficits were observed in HI rats compared with sham controls. The reduction in forelimb grasping strength in HI rats was attenuated by preconditioning with hypoxia, CoCl(2) and DFX. HI increased the number of foot faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder test. Only preconditioning with hypoxia reversed all three functional deficits after HI. These findings indicate that preconditioning, especially when induced by hypoxia, has the potential to minimize the morphologic and functional effects of neonatal HI injury.
Jones
Nicole M
NM
Brain Injury and Repair Group, Howard Florey Institute, University of Melbourne, VIC 3010 Melbourne, Victoria, Australia. nicole.jones@florey.edu.au
Kardashyan
Liubov
L
Callaway
Jennifer K
JK
Lee
Elizabeth M
EM
Beart
Philip M
PM
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003035:Cobalt / Q000494:pharmacology* / Q000627:therapeutic use; D003676:Deferoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018696:Neuroprotective Agents; D003035:Cobalt; C018021:cobaltous chloride; D003676:Deferoxamine