THE EFFECT OF AGE ON SUSCEPTIBILITY TO HYPOXIC-ISCHEMIC BRAIN-DAMAGE

Stroke occurs in all age groups, ranging from the new-born to the elde rly. Our current understanding of the mechanisms of ischemic brain inj ury suggests that, despite age, the underlying cascade of events inclu des the rapid depletion of energy reserves, lactate accumulation, rele ase of excitatory amino acids, high intracellular concentrations of Ca 2+, and the production of oxygen free radicals. The extent to which th ese events affect brain injury, however, is profoundly influenced by a ge. Hyperglycemia for example, markedly enhances hypoxic-ischemic brai n damage in adults, but has a protective effect in new-born rats. Insu lin-induced hypoglycemia, on the other hand, protects the adult brain, but may be detrimental to the new-born. Substrate utilization of keto ne bodies is markedly enhanced in the new-born, and has now been shown also to protect the brain. The immature brain is generally believed t o be more resistant to the damaging effects of cerebrovascular comprom ise compared to the more mature brain. However, recent experiments sug gest that the correlation between brain damage and age is not linear. To further clarify the effects of age and development on hypoxic-ische mic brain damage, we developed a model whereby rats of increasing age received identical cerebrovascular insults. 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 t hree age groups. Hippocampal damage was most severe in the 3-week and 6-month-old rats compared to all other age groups. These findings cont rast previously held beliefs regarding the enhanced tolerance of the i mmature brain to hypoxic-ischemic damage and demonstrate that the imma ture brain is, in fact, less resistant to hypoxic-ischemic brain damag e than its adult counterpart. The results emphasize the need for a gre ater understanding of the effects of ontogeny on hypoxic-ischemic brai n damage, particularly as it pertains to the development of therapeuti c interventions. (C) 1997 Elsevier Science Ltd. All rights reserved.