PROPENTOFYLLINE ADMINISTERED BY MICRODIALYSIS ATTENUATES ISCHEMIA-INDUCED HIPPOCAMPAL DAMAGE BUT NOT EXCITATORY AMINO-ACID RELEASE IN GERBILS

Systemic administration of propentofylline (PPF), an adenosine uptake inhibitor, has been demonstrated to protect CA1 pyramidal cells from d eath following transient cerebral ischemia in gerbils. In order to exa mine the direct effects of this inhibitor, we tested whether or not PP F administered into the hippocampus in situ through a microdialysis pr obe could attenuate ischemia-induced excitatory amino acid (EAA) relea se and prevent subsequent death of CA1 pyramidal cells in the gerbil. The EAA release and death of CA1 pyramidal cells observed in the hippo campus were compared with those in the contralateral hippocampus of th e same animal into which vehicle alone was administered. The results i ndicated that pre- as well as post-treatments with PPF inhibited the d eath of CA1 pyramidal cells after 5-min ischemia in a dose-dependent m anner, but did not significantly alter the EAA release during ischemia and reperfusion in the same animals. While the neuroprotective effect of PPF against ischemic damage has commonly been ascribed to attenuat ion of EAA release during ischemia, other actions of adenosine such as those influencing the synaptic responses, neuronal excitation, and lo cal cerebral circulation, or as yet unidentified actions may be involv ed in the observed neuroprotective effects of PPF.