Effect of seizures on cerebral hypoxic-ischemic lesions in immature rats

The present investigation was designed to study the effect of chemically in duced seizures on cerebral hypoxic-ischemic (HI) damage in immature animals . Accordingly, cerebral HI was produced in 7-day postnatal (p7) rats and p1 3 rats by combined unilateral common carotid artery ligation and hypoxia wi th 8% oxygen. Seizures were induced chemically by the subcutaneous injectio n of kainic acid (KA) or inhalation of flurothyl vapor. Three types of expe riments were conducted in each age group and for each convulsant. In some a nimals (group 1), seizures were produced at 24 h and again at 6 h prior to HI. In groups 2 and 3, seizures were induced 2 h or 24 h post HI, respectiv ely. The results indicate that in group 1 animals, the first seizure signif icantly reduced duration of the second seizure challenge 18 h later at both p7 and p13 (p = 0.001). Histologic examination of brains of animals in gro up 1 subjected to seizures prior to HI and their HI-only controls showed th at seizures prior to HT conferred protection against cerebral damage. This effect was significant for flurothyl seizures in p13 rats for all cerebral regions, especially hippocampal CA1 (p = 0.0004), and in p7 rats for hippoc ampus (p = 0.04) and particularly cerebral cortex (p = 0.007). For KA seizu res, the protective effect was only significant in p13 rats and was limited to hippocampal CA regions and subiculum (p = 0.0009). Histologic assessmen t of cerebral lesions of p7 and p13 rats in the other two groups showed no significant difference between the animals subjected to seizures 2 h or 24 h post HI and their HI-only controls (p > 0.05). In conclusion, the results of the present study provide no evidence that seizures in early postnatal development aggravate pre-existing cerebral HI damage. They do suggest that seizures prior to HI or prior to a second seizure confer tolerance to both conditions. (C) 1999 Elsevier Science B.V. All rights reserved.