Deferoxamine improves spatial memory performance following experimental brain injury in rats.
Traumatic brain injury (TBI) causes impairments of both motor and spatial memory performances. Research is only beginning to reveal the biochemical mechanism(s) underlying these deficits. It has been postulated that reactive oxygen species such as the superoxide and hydroxyl radicals, as well as the peroxynitrite anion, are generated by injury and may play a critical role in the observed memory deficits. The highly reactive hydroxyl radical, which is thought to contribute to neuronal toxicity, can be generated by an iron-catalyzed reaction. The source of this iron (or iron-bound proteins) could be a compromise of the blood-brain barrier, which can occur following TBI. In this report, we investigate the ability of deferoxamine, a scavenger of free iron, the hydroxyl radical and the peroxynitrite anion, to facilitate behavioral recovery following a controlled cortical impact of rats. Intraperitoneal administration of this drug prior to the injury did not affect the rate of recovery from motor deficits in comparison to vehicle (saline)-injected animals. However, deferoxamine-treated animals showed significant improvement in spatial memory performance in a Morris water maze task. Volumetric analysis of cortical tissue loss showed no significant differences between vehicle- and drug-injected animals. Similarly, histological examination of the hippocampus did not reveal any gross differences between the two groups. These results indicate that deferoxamine improves spatial memory performance, possibly through protection from neuronal dysfunction.
Long
D A
DA
Department of Neurobiology and Anatomy, University of Texas-Houston Health Science Center 77225, USA.
Ghosh
K
K
Moore
A N
AN
Dixon
C E
CE
Dash
P K
PK
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D048429:Cell Size / Q000502:physiology; D003676:Deferoxamine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000502:physiology; D009460:Neurologic Examination; D009474:Neurons / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000494:pharmacology*; D013037:Spatial Behavior / Q000187:drug effects*; D014722:Vestibule, Labyrinth / Q000502:physiology
D017262:Siderophores; D003676:Deferoxamine