ABSTRACT
Under normal conditions, the central nervous system (CNS) seldom encounters free hemoglobin because it is tightly compartmentalized within erythrocytes that, in turn, are contained within the vasculature. Following trauma, however, the blood-brain barrier is compromised, and vascular components spill into the neuropil; as the erythrocytes lyse, CNS cells are exposed to increasing concen trations of free hemoglobin. Hypothetically, a similar situation would occur if a hemoglobin-based oxygen carrier were infused into a patient with a breached blood-brain barrier-one who has suffered, for example, a head or spinal cord injury or hemorrhagic stroke. However, experiments modeling such a situation have not been performed in preclinical studies, and such a scenario is under standably being avoided in clinical studies. Regardless of the mechanism through which CNS tissue is exposed to hemoglobin, the ultimate threat to the CNS is hemoglobin-bound iron.
