PMID- 16623832
OWN - NLM
STAT- MEDLINE
DCOM- 20060530
LR  - 20131121
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 23
IP  - 7
DP  - 2006 Apr
TI  - Delayed administration of deferoxamine reduces brain damage and promotes 
      functional recovery after transient focal cerebral ischemia in the rat.
PG  - 1757-65
AB  - The mechanisms underlying functional recovery after stroke are poorly understood. 
      Brain-adaptive responses to the hypoxic stress elicited by ischemia could 
      contribute to these mechanisms. Indeed, hypoxia-inducible factor-1 (HIF-1), one 
      of the main transcriptional factors regulated by oxygen level, increases the 
      expression of several beneficial genes such as erythropoietin, glucose 
      transporter-1 and vascular endothelial growth factor. In order to strengthen the 
      expression of these hypoxia-inducible factors, we administered deferoxamine, an 
      iron chelator known to stabilize HIF-1alpha protein expression, and examined its 
      effects on the functional deficits induced by ischemia. Anesthetized 
      Sprague-Dawley rats were subjected to 60 min of intraluminal occlusion of the 
      middle cerebral artery. Chronic deferoxamine treatment (300 mg/kg, s.c.), or its 
      vehicle, started 24 h after ischemia and was continued bi-weekly until the 
      animals were killed. Sensorimotor deficits were periodically assessed over 2 
      months, and at this end point, the lesion volume was determined by histology. 
      Treatment with deferoxamine significantly decreased the size of brain damage 
      (-28%) after ischemia and improved behavioral recovery. Indeed, neurological 
      score and sensorimotor performances in the adhesive removal test recovered 
      earlier in the deferoxamine-treated animals. Moreover, the long-lasting skilled 
      forepaw reaching deficits were attenuated by deferoxamine. Although an 
      antioxidant effect of deferoxamine cannot be excluded, the hypothesis that its 
      beneficial effects could be mediated by an increase in HIF-1 target genes merits 
      further investigations. Our data suggest that delayed administration of 
      deferoxamine could represent an interesting therapeutical approach to treat focal 
      cerebral ischemia.
FAU - Freret, Thomas
AU  - Freret T
AD  - CNRS UMR 6185, Cyceron, University of Caen Basse-Normandie, Bvd H. Becquerel 
      F-14074 Caen cedex, France. thomas.freret@unicaen.fr
FAU - Valable, Samuel
AU  - Valable S
FAU - Chazalviel, Laurent
AU  - Chazalviel L
FAU - Saulnier, Romaric
AU  - Saulnier R
FAU - Mackenzie, Eric T
AU  - Mackenzie ET
FAU - Petit, Edwige
AU  - Petit E
FAU - Bernaudin, Myriam
AU  - Bernaudin M
FAU - Boulouard, Michel
AU  - Boulouard M
FAU - Schumann-Bard, Pascale
AU  - Schumann-Bard P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iron Chelating Agents)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain/*drug effects/pathology/physiopathology
MH  - Deferoxamine/administration & dosage/pharmacology/*therapeutic use
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis
MH  - Infarction, Middle Cerebral Artery/complications
MH  - Iron Chelating Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Ischemic Attack, Transient/*drug therapy/etiology/physiopathology
MH  - Male
MH  - Motor Activity/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2006/04/21 09:00
MHDA- 2006/05/31 09:00
CRDT- 2006/04/21 09:00
PHST- 2006/04/21 09:00 [pubmed]
PHST- 2006/05/31 09:00 [medline]
PHST- 2006/04/21 09:00 [entrez]
AID - EJN4699 [pii]
AID - 10.1111/j.1460-9568.2006.04699.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2006 Apr;23(7):1757-65. doi: 10.1111/j.1460-9568.2006.04699.x.