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 consists of a 7-day postnatal rat model with combined common carotid artery 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 distribution of lesions. It is not clear how and when during animals' development these changes in cerebral vulnerability take place. To determine this we studied groups of rats of 2 to 30 postnatal days. The animals underwent unilateral common carotid artery ligation followed by breathing in 8% oxygen for 30, 60, 90, or 120 min and their brains were examined at 24- or 72-h recovery intervals. Due to resistance of 2-3-day-old rats to develop cerebral hypoxic-ischemic damage, 5% O2 was used instead of 8% O2. The results indicate that: (i) There is an overall increase in severity of cerebral lesions on the side of common carotid artery ligation between 2 and 7 postnatal days. There is also an increase in the frequency of cerebral lesions in developing animals with increasing age. (ii) Hippocampus is remarkably resistant to hypoxic-ischemic insult at 2-3 postnatal days but becomes progressively vulnerable, and by age 13 postnatal days hippocampal vulnerability far exceeds that of cortex. (iii) Cortical lesions change from predominantly columnar cell death to laminar selective neuronal death at age 13 postnatal days. (iv) Also significant changes occur in relative vulnerability of various hippocampal regions during development. During the first 5 postnatal days relative vulnerability of hippocampal regions is similar, but as the animals' development proceeds and hippocampal vulnerability increases lesions tend to involve specific regions while sparing others. By age 13 postnatal days CA1 and lateral CA3 develop increased vulnerability while medial CA3 and fascia dentata become relatively resistant and by 21 postnatal days adult pattern of CA1 selective vulnerability is approached. The underlying mechanisms for these changes in regional vulnerability to cerebral hypoxia-ischemia during development should be sought in complex regional anatomic, functional, and metabolic alterations that take place as brain matures.
Towfighi
J
J
Department of Pathology (Anatomic Pathology), Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, USA.
Mauger
D
D
Vannucci
R C
RC
Vannucci
S J
SJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology; D002534:Hypoxia, Brain / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar