Reversibility of Ischemic Brain Damage

The susceptibility of the brain to anoxia is considered to be the limiting factor for resuscitation after transient circulatory arrest, both in clinical and experimental conditions.^1,2In the classic experiments of Weinberger et al,³Kabat et al,⁴Grenell,⁵Hirsch et al,⁶and others, the upper limit for full recovery was found to be three to four minutes of cardiocirculatory arrest, and eight to ten minutes of isolated cerebrovascular arrest. The high sensitivity of the central nervous tissue to ischemia has been attributed to low reserves in substrates suitable for anaerobic energy metabolism, because a close correlation was found between the depletion of energy-rich phosphates and the irreversibility of brain damage.⁷This concept, however, is difficult to reconcile with more recent demonstrations of the recovery of various neuronal functions after time intervals which by far exceed the limit of energy depletion. Examples are the return