THE EFFECT OF AGE ON SUSCEPTIBILITY TO BRAIN-DAMAGE IN A MODEL OF GLOBAL HEMISPHERIC HYPOXIA-ISCHEMIA

Stroke occurs in all age groups, ranging from the newborn to the elder ly. The immature brain is generally believed to be more resistant to t he damaging effects of cerebrovascular compromise compared to the more mature brain. However, recent experiments suggest that the correlatio n between brain damage and age is not linear. To determine the effects of age and development on hypoxic-ischemic brain damage, we developed a model whereby rats of increasing age received identical cerebrovasc ular insults, and assessed neuropathologic outcome. Male Wistar rats o f 1, 3, 6, and 9 weeks and 6 months underwent unilateral common caroti d artery ligation and exposure to 12% oxygen for 35 min. Animals were all spontaneously breathing under Light halothane anesthesia (0.5%). C ore temperatures were maintained at 37 degrees C. Blood pressures were monitored via indwelling carotid artery catheters on the side ipsilat eral to the carotid artery ligation. Cerebral blood flow was assessed in separate groups utilizing Laser Doppler flowmetry. Physiologic moni toring revealed that under these experimental conditions, mean arteria l blood pressure and cerebral blood flow decreased to the same extent in each of the age groups, verifying that all animals experienced an i dentical insult. Neuropathologic assessment at 7 days of recovery show ed that brain damage was most severe in the 1 and 3 week old animals f ollowed by those that were 6 months. The 6 and 9 week old groups had s ignificantly less injury than the other 3 age groups. Kippocampal dama ge was most severe in the 3 week and 6 month old rats compared to all other age groups. Our findings contrast previously held beliefs regard ing the enhanced tolerance of the immature brain to hypoxic-ischemic d amage and demonstrates that, in a physiologically controlled in vivo m odel of hemispheric global ischemia, (1) the immature brain is, in fac t, less resistant to hypoxic-ischemic brain damage than its adult coun terpart, (2) the brain damaging effects of hypoxic-ischemia are age de pendent, but do not increase linearly with advancing age and developme nt, and (3) the intermediate age groups are more tolerant to hypoxic-i schemic brain injury than either very young or more mature ages.