Translation experiments in traumatic brain injury ... is it time to renew pharmacologic therapy?

摘要

Hellmich et al. (i) in an interesting article published recently, discuss two compounds that provide neuroprotection in the hippocampus. These are metyrapone (MT) and carbe-noxolone (CB), which exert their neuroprotective and memory-enhancing effects by inhibition of a common molecular target. Each compound inhibits the gene coding for nb hydroxyste-roid dehydrogenase type i, which converts inactive cortisone to active cortisol in the brain. These glucocorticoids have been shown to impair the ability of neurons to block cascades of glutamate and calcium during TBI, thus exacerbating cyto-skeletal pathology and neuron death. However, pathway analysis in their work confirmed that the neuroprotective effects of MT and CB are mediated, in part, by common molecular targets other than nb hydroxysteroid dehydrogenase type I.