THE EFFECT OF AGE ON SUSCEPTIBILITY TO HYPOXIC-ISCHEMIC (H-I) BRAIN DAMAGE.▴ 2282

Abstract

The immature brain is believed to be more resistant to the damaging effects of H-I compared to the more mature brain. However, recent experiments suggest that the correlation between brain damage and age is not linear. To determine the effects of age and development on H-I brain damage, we developed a model whereby rats of increasing age received identical cerebrovascular insults, and assessed neuropathologic outcome. Male Wistar rats of 1, 3, 6, and 9 weeks and 6 months underwent unilateral common carotid artery ligation and exposure to 12% oxygen for 35 minutes. Animals were all spontaneously breathing under light halothane anesthesia (0.5%). Core temperatures were maintained at 37°C. Blood pressures were monitored via indwelling carotid or femoral catheters. Cerebral blood flow was assessed in separate groups utilizing Laser Doppler flowmetry. Physiologic monitoring revealed that under these experimental conditions, mean arterial blood pressure and cerebral blood flow decreased to the same extent in each of the age groups, verifying that all animals experienced an identical insult. Neuropathologic assessment at 7 days of recovery showed that brain damage was most severe in the 1 and 3 week old animals followed by those that were 6 months. The 6 and 9 week old groups had significantly less injury than the other 3 age groups. Hippocampal damage was most severe in the 3 week and 6 month old rats compared to all other age groups. Our findings contrast previously held beliefs regarding the enhanced tolerance of the immature brain to H-I damage and demonstrates that, in a physiologically controlled in vivo model of hemispheric global ischemia, 1) the immature brain is less resistant to H-I brain damage than it's adult counterpart, 2) the brain damaging effects of H-I are age dependent, but do not increase linearly with advancing age and development, and 3) intermediate age groups are most tolerant to H-I brain injury.