Neuroprotection

Neuroprotection describes strategies aimed at keeping neurons alive and functional during or after an injurious process such as ischaemia, trauma or a neurodegenerative cascade. The targets are secondary injury mechanisms rather than the initial insult: glutamate excitotoxicity and calcium influx, free radical damage, mitochondrial failure, apoptosis and glial activation. It is defined against symptomatic treatment, which improves function without altering tissue loss.

The translational record is the most instructive part of the field. Hundreds of agents have reduced infarct volume in rodent stroke models and essentially none have delivered a functional benefit in humans. The free radical trapping agent NXY-059 was positive in one large stroke trial and flatly negative in its replication. The nerinetide trial in thrombectomy-eligible stroke patients missed its primary outcome. Edaravone is approved for amyotrophic lateral sclerosis on a modest functional-scale difference in a narrowly selected population, which is about as good as this class has managed.

That history is why the field wrote the STAIR recommendations: blinded and randomised animal work, dose-response data, physiological monitoring, clinically relevant outcome measures, and replication in a second species and a second laboratory. Reading a neuroprotection claim means asking which conditions the underlying study met, and whether the outcome was tissue volume or function weeks later.

The error that recurs is treating a histological endpoint as a clinical one. Smaller lesion area, fewer TUNEL-positive cells or better cell viability in culture are all upstream of the only question that matters, which is whether the animal or the patient functions better. Culture experiments compound this by using concentrations no plausible dosing could achieve in brain.