Effects of entorhinal lesions on trophic activities present in rat entorhinal cortex and hippocampus as studied using primary cultures of entorhinal and septal tissues.

The present study examined trophic activities in normal and injured brain which affect the survival and growth of central neurons in culture. Adult rats received bilateral lesions through the angular bundle, severing projections between the entorhinal cortex and the hippocampus. Ten days later, extracts were prepared from the entorhinal or hippocampal regions of the injured brains and compared with extract prepared from analogous regions of normal brains for trophic activities in cultures of either entorhinal or septal tissues. At least three activities were observed: (1) a trophic activity which bound to polylysine-treated wells, which was greater than 10,000 Da in size, heat labile, and sensitive to trypsin, and which supported the survival of both septal and entorhinal neurons in culture; (2) a trophic activity which did not bind to polylysine-treated wells, which was greater than 10,000 Da in size, heat labile, and sensitive to trypsin, and which, in the presence of polylysine-bindable material, facilitated the survival and growth of entorhinal cells in culture, and (3) an inhibitory activity which significantly reduced survival in entorhinal cultures when cells were plated in the presence of high concentrations of extract prepared from normal brain. These effects were not due to nonspecific effects of plating the cells in, or treating the wells with, large amounts of protein. A significant injury-related increase in non-polylysine-bindable trophic activity was also observed. Extracts prepared from either the hippocampus or the entorhinal area of the injured brains contained more non-polylysine-bindable trophic activity than extract prepared from normal brains. Injury-related changes in trophic activities were more prominent in entorhinal than in septal cultures. This increase in activity may account for the injury-related effects on the survival of entorhinal transplants reported previously [Gibbs and Cotman: Neuroscience (in press) 1987], and may represent an endogenous mechanism by which the brain attempts to selectively support the survival of injured cells following injury.