Methods and pharmaceutical compositions for preconditioning and / or providing
neuroprotection to the animal
central nervous system against the effects of
ischemia, trauma,
metal poisoning and
neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. Patients at risk for certain diseases or disorders that are associated with risk for cerebral
ischemia may benefit, e.g., those at risk for Alzheimer's
disease, Parkinson's
disease, Wilson's
disease or
stroke or those patients having head or
spinal cord injury. Patients undergoing certain medical procedures that may result in
ischemia may also benefit. Initially, the possibility of ischemia or
neurodegeneration is recognized. Intranasal therapeutic agents are administered to the
upper third of the
nasal cavity to bypass the blood-brain barrier and access the
central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and / or
copper such as iron chelators,
copper chelators, and antioxidants. A particular example of such therapeutic agents is the
iron chelator deferoxamine (DFO). Intranasal administration of DFO is known to stimulate and / or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia. Moreover, DFO is shown to
decrease weight loss in subjects when administered pre and / or
post stroke.