INFLUENCE OF AGE ON THE CEREBRAL-LESIONS IN AN IMMATURE RAT MODEL OF CEREBRAL HYPOXIA-ISCHEMIA - A LIGHT-MICROSCOPIC STUDY

The most frequently used model of neonatal cerebral hypoxia-ischemia c onsists of a 7-day postnatal rat model with combined common carotid ar tery ligation and hypoxemia, Neuropathologic studies have shown major differences between this 7-day postnatal rat model and a similar adult model in regard to overall cerebral vulnerability, type and distribut ion of lesions. It is not clear how and when during animals' developme nt these changes in cerebral vulnerability take place. To determine th is we studied groups of rats of 2 to 30 postnatal days. The animals un derwent unilateral common carotid artery Ligation followed by breathin g in 8% oxygen for 30, 60, 90, or 120 min and their brains were examin ed at 24- or 72-h recovery intervals. Due to resistance Of 2-3-day-old rats to develop cerebral hypoxic-ischemic damage, 5% O-2 was used ins tead of 8% O-2. The results indicate that: (i) There is an overall inc rease in severity of cerebral lesions on the side of common carotid ar tery ligation between 2 and 7 postnatal days. There is also an increas e in the frequency of cerebral lesions in developing animals with incr easing age. (ii) Hippocampus is remarkably resistant to hypoxic-ischem ic insult at 2-3 postnatal days but becomes progressively vulnerable, and by age 13 postnatal days hippocampal vulnerability far exceeds tha t of cortex. (iii) Cortical lesions change from predominantly columnar cell death to laminar selective neuronal death at age 13 postnatal da ys. (iv) Also significant changes occur in relative vulnerability of v arious hippocampal regions during development. During the first 5 post natal days relative vulnerability of hippocampal regions is similar, b ut as the animals' development proceeds and hippocampal vulnerability increases lesions tend to involve specific regions while sparing other s. By age 13 postnatal days CA1 and lateral CA3 develop increased vuln erability while medial CA3 and fascia dentata become relatively resist ant and by 21 postnatal days adult pattern of CA1 selective vulnerabil ity is approached. The underlying mechanisms for these changes in regi onal vulnerability to cerebral hypoxia-ischemia during development sho uld be sought in complex regional anatomic, functional, and metabolic alterations that take place as brain matures.