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Studies on the effects of hemoglobin on synaptic transmission in the hippocampus

University of British Columbia

During head injuries and hemorrhagic stroke, blood is released into the extravascular space. The pooled blood remains in the intracranial cavity for a prolonged period of time. During this time, it has been shown that the pooled erythrocytes get lysed and hemoglobin is released into the intracranial cavities. Since clearance of hemoglobin is slow, neurons may be exposed to hemoglobin and/or its breakdown products, hemin and iron, for long periods of time. It is, therefore, important to understand the effects of hemoglobin and its breakdown products on synaptic transmission. In this study, the electrophysiological actions of these agents on synaptic transmission in rat hippocampal CA1 pyramidal neurons were studied using extracellular field- and whole cell patch-recordings. It was found that commercially available hemoglobin samples produce inconsistent effects on synaptic transmission in hippocampal slices. The commercial hemoglobin which reversibly depressed synaptic transmission in CA1 neurons, was found to be contaminated with ammonium and bisulfate. These agents may be responsible for the observed synaptic depression. Since commercially available hemoglobin contains both methemoglobin and reduced-hemoglobin, the effects of these compounds were studied on synaptic transmission. Methemoglobin had no significant effect on synaptic transmission. Although reduced-hemoglobin, prepared with a method described by Martin et al. (1985), produced a significant reversible depression of synaptic transients, the effects were actually due to the bisulfite that was introduced by the reducing procedure. Unlike hemoglobin, breakdown products of hemoglobin, ferrous chloride and hemin, produced a significant irreversible depression of field excitatory postsynaptic potentials. The importance of these effects of hemoglobin breakdown products in understanding neurological complications that follow head-injuries and hemorrhagic stroke awaits further investigation.

Thesis/Dissertation

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2009-07-20

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http://hdl.handle.net/2429/10992

Pharmacology

University of British Columbia

UBCV

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