Temporal profile of adenovirus-mediated E. coli lacZ gene expression in normal and post-ischemic gerbil hippocampus and ventricle

Abstract

A replication-defective adenoviral vector containing the E. coli lacZ gene was directly injected into normal and post-ischemic gerbil right hippocampus and lateral ventricle, and temporal profiles of the exogenous gene expression were compared. In case of ischemia, common carotid arteries (CCA) were transiently occluded for 5 min, and the adenoviral vector was administered just after the reperfusion. The animals were recovered for 8 h, 1, 3, 7 or 21 days. A small to moderate number of neural cells in the normal hippocampus expressed the gene from 1-3 days except for the cells around dentate gyrus (DG) and the needle route that began to express from 8 h of injection. Some normal hippocampal cells persisted the expression until 7 days. A moderate to large number of ventricular cells expressed the lacZ gene from 8 h to 7 days in the normal brain. On the other hand, no expression of the lacZ gene was observed in the post-ischemic hippocampus at 8 h including cells at DG and the needle route. Hippocampal CA1 neurons, that were selectively lost at 7 days of reperfusion, never expressed the gene throughout the post-ischemic course. The other hippocampal cells such as CA3 and dentate granule cells that survived ischemia expressed the gene only transiently at 1 day. A robust expression of the gene persisted in the ventricular cells from 8 h to 7 days. The majority of brain cells in the hippocampus that expressed the lacZ gene was not the pyramidal neurons, but small neurons at around the pyramidal layers of DG. Some astroglial, but no microglial, cells expressed the lacZ gene in the hippocampus. The present study shows that an expression of the lacZ gene was limited in the post-ischemic gerbil hippocampus especially at the vulnerable CA1 layer in contrast to the strong and persistent expression in the ventricular cells, and that the majority of beta-gal positive cells were not the pyramidal neurons but small neurons at around the cell layer both in the control and post-ischemic gerbil hippocampus.