To: Dr. Bob who wrote (163 ) 11/12/1997 9:23:00 AM From: NeuroInvestment Read Replies (2) | Respond to
It is true that there is no dearth of agents that, if we could all have them administered just prior to the stroke/head trauma, work quite well as neuroprotectants, but do not 'rescue' neurons already impacted. However, keep in mind that upstream/downstream depictions of the locus of intervention are at the neuron level. There is also a gross topographical level wherein neuron death gradually expands out from the core infarct, involving more and more of the ischemic penumbra. From that point of view, if one provides an upstream neuroprotectant such as a NAALADase inhibitor within some window of opportunity following an infarct, it will provide upstream protection of neurons not yet compromised, and with (in theory) lesser risk of adverse effects. However, your point is well taken, in that those neurons wherein calcium influx has already occurred would likely not be 'rescued' by an upstream intervention. My view has always been that polypharmacy will be the ultimate route, other agents that work downstream ( free radical scavengers, citicoline, small molecule neurotrophins, perhaps PARP-inhibitors) may also be needed to 'rescue' already involved neurons. Perhaps lower doses of these would be needed, reducing side effects. Thus far, GLFD has used NAALADase inhibitors in an animal model, giving it two hours after the insult. They report 65-85% reduction in the size of the ultimate lesion compared to controls. This indicates the possible role of the compound in arresting the 'spread' of excitotoxicity through the penumbra. Hope this clarifies the issue. NeuroInvestment
