Effect of Glucocorticoid-Induced Hyperglycemia on Preventing Hypoxic-Ischemic Brain Damage by Dexamethasone in Neonatal Rat.
- Author:
Kook In PARK
;
Tae Seung KIM
;
Min Soo PARK
;
Moon Sung PARK
;
Ran NAMGUNG
;
Chul LEE
;
Dong Gwan HAN
- Publication Type:Original Article
- MeSH:
Animals;
Anoxia;
Atrophy;
Blood Glucose;
Brain Injuries;
Brain*;
Carotid Artery, Common;
Cerebral Infarction;
Cerebrum;
Dexamethasone*;
Hippocampus;
Hyperglycemia*;
Hypoxia-Ischemia, Brain;
Incidence;
Insulin;
Mortality;
Neuroprotective Agents;
Oxygen;
Rats*
- From:Journal of the Korean Pediatric Society
1994;37(8):1035-1047
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Objective: We evaluated the protective effect of dexamethasone (DX) administration on brain damage produced in a perinatal model of cerebral hypoxia-ischemia in the rat. Since hyperglycemia has been shown to reduce hypoxic-ischemic brain injury (HI) in immature tar, we investigated the role of glucocorticoid-induced hyperglycemia in the neuroprotective mechanism of DX. Methods: Hypoxic-ischemic brain injury in 7-day-old rats was induced by right common carotid artery occlusion and 2 hours of 8% oxygen. Pups received 3 doses of DX (0.5mg/kg/d intraperitoneally) 48 hours, 24 hours and immediately before HI (Dx1)(n=12), a single dose of DX 24 hours(DX2)(n=16), 3 hours (DX3)(N=10)or immediately before HI (DX4)(n=14), a single dose of DX immediately after HI (DX5) (n=9), 3 doses of DX immediately, 24 hours and 48 hours after HI (DX6) (n=14) and a single dose of DX 24 hours before HI with insulin (0.5U/kg, subcutaneously, 1.5 hours before HI)(IN)(n=8). Control pups (n=15) received a single dose of normal saline 24 hours before HI. Blood glucose was estimated before hypoxia, 1 hour and 2 hours after hypoxia using glucometer in DX 1~4. IN and control rats. Pups were killed at 14 days of age for determination of mortality during HI, gross cerebral infarction and right cerebral hemisphere atrophy. We measured the diameter of each cerebral hemisphere and cortical thickness from a coronal section at the dorsal hippocampus level, and expressed the % atrophy from the change in the right vs left hemisphere diameter. Results: The mortality that occurred during and after HI was similar in all groups. The incidence of gross cerebral infarction was 0.0%, 0.0%, 75.0%, 83.3%, 87.5%, and 90.0% in DX 1~6, respectively, 0.0%in IN, and 100.0% in control group. There was a significant difference (p<0.001)in the incidence of gross cerebral infarction of DX1, DX2, IN vs control group. The mean % atrophy was 5.4 +/- 2.2, 4.9 +/- 1.8, 21.7 +/- 8.1, 29.7 +/- 5.0, 37.4 +/- 5.5, 33.4 +/- 9.3 in DX 1~6, respectively, 1.5 +/- 1.1 in IN, and 29.1 +/- 3.4 (mean+/-SEM) in control group. There was a significant difference in % atrophy of DX1, DX2, IN vs control group. Before hypoxia, there was no significant difference in blood glucose between saline, all DX, and DX with insulin treated groups. But after hypoxia, pups in DX1 and Dx2 were more hyperglycemic compared to DX 3~4, IN, or saline treated groups. Conclusions: Dexamethasone administration in the neonatal period protects the brain during the subsequent periods of hypoxia-ischemia in rats and glucocorticoid-induced hyperglycemia does not explain the neuroprotective effects dexamethasone.
