Extravascular polling of blood is usually associated with hemorrhagic stroke and head injuries. Central neurons can, therefore, be exposed to hemoglobin as a consequence of the bleeding. Neurological complications that follow a stroke episode or head injury can be quire debilitating and yet, the mechanisms involved in the onset of the neurological dysfunction are not understood. It is possible that the exposure of the neurons to hemoglobin can result in a change in their behavior leading to neurological complications in the patients. The actions of hemoglobin on central neurons are, however, not clear. It is necessary that these are understood before the involvement of hemoglobin in neurological complications can be determined. Epilepsy and memory deficits occur in some victims of head injuries and stroke. The hippocampus is susceptible to epileptic activity and is extensively studied to examine cellular mechanisms of learning and memory. In this proposal, experiments on the rat hippocampal slices are designed to examine the actions of hemoglobin on the CA1 pyramidal cells. Electrophysiological techniques, including intracellular recordings from CA1 neurons, will be employed. The following are the objectives for the next three years.
Specific aim 1 : to determine the actions on the CA1 pyramidal neurons of acute (short-duration or prolonged) applications of hemoglobin on the EPSPs, GABA-A IPSP's, GABA-B IPSPs, the membrane potential, input resistance and the ability to discharge action potentials. If the agent has actions on any of these, we shall (1a) determine dose-response relationships for the effects (1b) examine the mechanisms of action of hemoglobin, and (1c) find whether the exposure of the hippocampal slices to hemoglobin leads to long-term changes in the cell excitability.
Specific aim 2 : to examine if these actions of hemoglobin are (a) through an interference with nitric oxide (since there is evidence in literature that hemoglobin scavenges nitric oxide), (b) due to its iron contents and (c) due to its constituents, heme and globin. It is anticipated that the results of these studies will clarify the actions of hemoglobin in the hippocampal CA1 area and will from a scientific basis to determine if any of these actions are related neurological complications associated with stroke or head injury.
