Of importance to future research directions utilizing PPF is the novel finding in
1987 that PPF decreased GFAP immunoreactivity in the CA1 region of the hippocampus
following transient cerebral ischemia (Fig. 3). This was the first indication
of a direct glial modulating action which would not be fully realized until almost a
decade later. It was proposed by Schubert and others that pathological microglial
activation contributes to progressive neuronal damage in neurodegenerative
diseases by the release of potentially toxic agents and by triggering reactive
astrocytic changes (Schubert et al. 1997). With use of primary neonatal cultured
microglia, it was demonstrated that PPF enhanced cAMP-dependent intracellular
signaling (Si et al. 1998). PPF dose-dependently inhibited lipopolysaccharideinduced
release of both tumor necrosis factor a (TNFa) and interleukin (IL)-1b