DEFEROXAMINE IMPROVES SPATIAL MEMORY PERFORMANCE FOLLOWING EXPERIMENTAL BRAIN INJURY IN RATS

Traumatic brain injury (TBI) causes impairments of both motor and spat ial memory performances. Research is only beginning to reveal the bioc hemical mechanism(s) underlying these deficits. It has been postulated that reactive oxygen species such as the superoxide and hydroxyl radi cals, as well as the peroxynitrite anion,are generated by injury and m ay play a critical role in the observed memory deficits. The highly re active hydroxyl radical, which is thought to contribute to neuronal to xicity, 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 inves tigate the ability of deferoxamine, a scavenger of free iron, the hydr oxyl radical and the peroxynitrite anion, to facilitate behavioral rec overy following a controlled cortical impact of rats. Intraperitoneal administration of this drug prior to the injury did not affect the rat e of recovery from motor deficits in comparison to vehicle (saline)-in jected animals. However, deferoxamine-treated animals showed significa nt improvement in spatial memory performance in a Morris water maze ta sk. Volumetric analysis of cortical tissue loss showed no significant differences between vehicle- and drug-injected animals. Similarly, his tological examination of the hippocampus did not reveal any gross diff erences between the two groups. These results indicate that deferoxami ne improves spatial memory performance, possibly through protection fr om neuronal dysfunction.