Effects of neuroprotective cocktails on hippocampal neuron death in an in vitro model of cerebral ischemia

Cocktails of neuroprotectants acting at different parts of the ischemic inj ury cascade may have advantages over single agents. This study investigated , singly and in combination, the neuroprotective efficacy of an energy subs trate (3.5 mM fructose 1,6-bisphosphate, FBP), an antagonist of NMDA recept ors (1 and 10 muM MK-801), a free-radical scavenger (100 muM ascorbate), an adenosine Al receptor agonist (10 muM 2-chloroadenosine), and an inhibitor of neurotransmission (2% isoflurane). These agents were evaluated for thei r ability to prevent loss and morphologic damage of CA1 neurons in rat hipp ocampal slices when these agents were administered during 30 minutes in vit ro ischemia (combined oxygen/glucose deprivation at 37 degreesC) followed b y 5 hours of recovery. Ten muM MK-801, alone or in combination with the oth er compounds, prevented loss of CA1 neurons and preserved their histologic appearance. Isoflurane, which prevents glutamate receptor-dependent cell de ath in this model, was also protective. Protection against neuron loss was also found when a subtherapeutic concentration of MK-801 (1 muM) was combin ed with 2-chloroadenosine (which indirectly causes NMDA receptor suppressio n), but not FBP or ascorbate. The authors conclude that in this model, the strategy of antagonizing NMDA receptors appears more protective than fructo se-1,6-bisphosphate, 2-chloroadenosine or ascorbate.