Advances in understanding protection from cerebral ischemia

Cerebral ischemia and protection is a large field, so for the purposes of this review, which focuses on results published in the last 9 months, we have chosen to discuss a few aspects of ischemia in which our understanding has advanced significantly in this period of time. Recent progress in the clinical use of hypothermia for neurological protection as well as laboratory progress on the role of stress proteins, estrogen and a few other potential adjuncts will be discussed.

Two papers have now been published documenting improved neurological outcome in patients treated with hypothermia following cardiac arrest, both using randomized clinical trial designs. These reports and several laboratory studies identifying mechanisms of hypothermic brain protection are reviewed. In understanding the mechanisms underlying protection by estrogens, new results on both direct vascular effects and a demonstration that estrogens can reduce apoptosis are presented. The third area to be described is current progress in identifying mechanisms of stress protein protection from ischemia, in which new mechanisms have been identified with the demonstration of inhibition of several points in the cell death cascade. The remaining areas considered touch on the effects of approaches that reduce inflammation by blocking adhesion molecules, those that reduce free radical production and those that improve blood rheology.

An important common theme in brain protection is reduction of cell death by blocking apoptosis or programmed cell death. While the use of hypothermia should now enter clinical practice, many areas of brain injury require further studies both to define injury mechanisms and to translate these understandings into clinically useful treatments to reduce ischemic brain injury.