Cholinergic deafferentation prevents delayed neuronal death of the hippocampal CA1 pyramidal neurons after transient forebrain ischaemia.

Abstract

The relation between CA1 neurons, fimbria-fornix and cholinergic neurons of the basal forebrain was examined with the aid of Acetylcholine esterase (AChE) staining, Woelcke's staining and immunohistochemistry of Choline-acetyl transferase (ChAT). The transected side of the hippocampus was poorly stained by AChE two weeks after the transection, when the ipsilateral medial septum ChAT-positive neurons were reduced, but showed good recovery with AChE six weeks later. Nerve growth factor (NGF) was added at a dose of 10 micrograms/100 microliters immediately after the aspiration, and after that once per week with cisternal puncture. As a result, ipsilateral medial septum ChAT-positive neurons were preserved, but cross innervation with relation to hypertrophy of the cholinergic neurons was not detectable even six weeks after the transection. Furthermore, delayed CA1 neuronal death on the transected side of the hippocampus following occlusion of four vessels for 30 minutes was not detectable two weeks after the operation, although neuronal density was reduced after six weeks. The density of neurons on the transected side of the hippocampus in the CA1 subfield with treated NGF had not decreased significantly six weeks later. Therefore, we suspect that the input from cholinergic fibres must be transported to the hippocampal pyramidal neurons responding to NGF, and it was confirmed that cholinergic deafferentation prevents the delayed neuronal death of CA1 pyramidal neurons during transient ischaemia.