[Bench to bedside, tertiary centres to developing world --"tailoring" best available neuroprotection in high and low...

Neuroprotection following brain injury has been a top priority in neuroscience since the Hippocratic era. However, of hundreds of "experimentally-neuroprotective treatments", currently only hypothermia is clinically available. Interpretation of bench-work may have to account for the variation in developmental stages and types of injury. For example GABAergic stimulators have been used to reduce cerebral energy consumption; recent studies suggested the paradoxical excitation of premature neurons following GABAergic stimuli because of the high intracellular chloride concentration during the perinatal period. Even for hypothermia, many questions remain unanswered:selective-head cooling following perinatal hypoxia-ischemia appeared rather deleterious for infants with the most severe encephalopathy or low birth-weight. In a piglet model, different cooling levels provided differential regional brain protection:35 degrees C was optimal for deep-grey-matter whereas the cortical-grey-matter was better protected at 33 degrees C, suggesting that a single cooling level may not be equally optimal for the entire brain. Another experimental study used magnetic-resonance spectroscopy to demonstrate that the more severe the acute event was, the shorter the therapeutic time window was, explaining the lower effectiveness of neuroprotection following the most severe hypoxia-ischemia. Another suggestion from our translational research was the dependence of cerebral temperatures on body weight under selective-head cooling:the smaller the body weight, the lower the brain temperature, presumably because of the larger surface area to brain volume ratio in small subjects. Thus translational research is essential to achieve "tailored" treatments, that address for individual and regional cerebral conditions. Although therapeutic options have become available in the tertiary centre settings, neuroprotection should not remain an expensive treatment only available in rich countries. We have recently developed a cooling system that can maintain stable hypothermia over 24 hours without an electric supply. Experimental studies to optimise high-tech cooling need to run in parallel with studies to increase the distribution of these treatments worldwide.