Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABA(A) receptors

Background: The mechanism of the neuroprotective effects of propofol was co mpared to two other types of intravenous (i.v.) anesthetics (i.e., benzodia zepine; midazolam and barbiturate; pentobarbital) using Mongolian gerbils f ocusing on GABA receptor subtypes. Methods: Neuronal injury was induced by a 4-min occlusion of the common car otid arteries followed by reperfusion. One week after occlusion, animals we re transcardially perfused for histochemistry. Neuronal death in four brain regions was evaluated by direct visual counting of acidophilic neurons. Results: Seven days after this ischemic episode, severe neuronal injury was measured in the hippocampal CA1 area (>98% of total cells damaged) and par ietal cortex (>35%). Also lateral thalamus and caudate putamen were damaged but to a lesser extent (about 10%). The neuronal injury in these areas was significantly attenuated by propofol, midazolam and the GABAA agonist, mus cimol, intraperitoneally administered 15 min prior to ischemia. This neurop rotective property however, was lacking with pentobarbital and GABA(B) agon ist baclofen. Concomitant pretreatment with subthreshold doses of propofol and muscimol significantly reduced the amount of cell death induced by brai n ischemia. On the other hand, pretreatment with the GABA(A) antagonist bic uculline significantly inhibited the neuroprotective effects of propofol. H owever, a GABA(B) antagonist, phaclofen, was without effect on neuronal dam age and on neuronal protection of propofol. Conclusion: These results indicate that activation of GABA(A) receptors, wh ich include the specific binding subunits for propofol and midazolam, but n ot pentobarbital, plays a role in the inhibition of neuronal death induced by brain ischemia.