Chronic intraventricular norepinephrine and delayed neuronal death in the hippocampus

The present studies evaluated the effect of chronic intraventricular microinfusion of norepinephrine (NE) to examine if higher levels of intracerebral NE could protect agonists the development of delayed neuronal death (DND) in the hippocampus of a transient forebrain ischaemia model. Small cannulas connected to osmotic minipumps were stereotactically placed in the lateral ventricle, and NE (40 muM) was pumped at the rate of 0.5 mu1/hour for periods of up to 14 days. Brain tissue was then analysed for the total NE content at 2.5 mm intervals from the cannula tip, using high pressure liquid chromatography. The result of these preliminary studies showed a 5 to 40-fold increase in the NE levels in the specimens on the infusion side and a 2 to 3-fold increase on the non-infusion side. The number of surviving pyramidal neurones in the hippocampal CA1 region were then compared between the ipsilateral and contralateral hemispheres of the brains obtained from experimental and control animals. Significant suppression of neuroanal death was demonstrated in the presence of increased levels of exogenous NE on the infusion side. These studies suggest that intraventricular administration of NE is feasible and that the resulting higher levels of NE may attenuate the phenomena of DND in the hippocampus, possibly by a direct protective action upon the neurones.