PERIPHERAL TYPE BENZODIAZEPINE BINDING-SITES FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT - EFFECT OF NEUROPROTECTIVE DRUGS

Recent studies have demonstrated that measurement of peripheral type benzodiazepine binding sites (PTBBS) levels may be useful as an index for quantification of neuronal damage. In the present study, we investigated the accuracy of this index as a marker of neuronal damage induced by transient forebrain ischemia in the rat (4-vessel occlusion model). Seven days after ischemia, a good correlation was found between the increase of PTBBS levels (measured using [H-3]PK 11195 as a specific radioligand) in hippocampal, striatal and cortical homogenates and the duration of ischemia. The progression of PTBBS increase was examined from 3 h to 14 days of recirculation. Increase in the maximal number of binding sites (B(max)) rather than an effect of the affinity (K(D)) for the radioligand was found in the 3 brain regions. Treatment of the animals with 1,3 butanediol (BD) prior to ischemia resulted in a neuroprotective effect as assessed by an improved neurological score and histological studies. The protective effect of BD was also correlated with a reduced expression of PTBBS as compared to ischemic animals not treated with the drug. No protective effects, on neurological score or PTBBS level were afforded by MK-801, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, R-phenylisopropyladenosine (RPIA), an adenosine A1 receptor agonist, or BN 52021, an antagonist of platelet-activating factor (PAF). These results suggest that PTBBS provide a useful marker of neuronal damage in a transient forebrain ischemia model and confirm the beneficial effect on ischemic damage exerted by BD.