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Neurotoxicity and behavioral performance degradation have previously been observed in rats after exchange transfusions with unmodified stroma-free hemoglobin solutions. We evaluated a diaspirin cross-linked stroma-free hemoglobin solution (HbXL) for evidence of neurotoxicity. Rats that were trained to complete a water alley maze received a clinically-relevant dose (20 ml/kg) of the 14% HbXL solution on top of their normal blood volume. After post-treatment memory testing in the water maze, the same rats were challenged to learn an elevated radial-arm maze. The HbXL and control groups showed no water maze performance degradation after treatment, and all groups demonstrated learning of the radial-arm maze as shown by decreased errors and times to completion. The brains, heart, and livers presented normal histology thirty days after infusion, but six of fifteen animals showed marked renal tubular regeneration. The normal memory and learning performance and brain histology after infusion with HbXL suggests that this hemoglobin solution is not neurotoxic to unhemorrhaged rats.

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