Effects of Dexamethasone in Hypoxic-Ischemic Brain Injury in the Rats

The effect of high dose of glucocorticoid in acute spinal cord injury has been well proved experimentally and clinically. In addition, the beneficial effect of steroids in cerebral vasogenic edema has been well documented and clinically steroids are now a part of the treatment of intracranial neoplasms. Consequent trials of high dose steroid therapy in CNS injury have been proved its ineffectiveness or adverse effecis in clinical and experimental studies. Also, dexamethasone treatment in hypoxic-ischemic brain damage in rats showed adverse effects on neurons in most of the studies in adult and immature rats, except one report which showed neuroprotective effects of dexamethasone pretreatment in 7-day-old immature rats.

This study was designed to see if there was same neuroprotective effect in adult rat since no previous experiments used same amounts of steroid at this time intervals. Hypoxic-ischemic injury was induced in adult Sprague-Dawley rats, 150~240 gms, by Levine procedure with some modification (left carotid artery ligation and exposure to 8% oxygen-92% nitrogen gas for 2 hours). The animals were divided into four groups and dexamethasone was injected as follows : (I) hypoxic-ischemic control group without dexamethasone injection(n=16) ; (II) 0.5mg/kg i.p. 3 times, 48 and 24 hours, and immediately before the carotid artery ligation and 8% oxygen treatment(n=16) ; (III) 2.0mg/kg at same time with (II) (n=14) ; (IV) 1.0gm/kg 3 times at immediately after, 24 and 48 hours after the procedure(n=20). The neuropathological changes were interpreted 7 days after the procedure.

The results are summarized as follows :

1) In hypoxic-ischemic control group(I), 5 out of 16 rats(31.3%) of rats showed large infarction involving ipsilateral side of the brain and other 4~5 rats showed severe neuronal damage in anterior and posterior cortex, hippocampus, striatum, and thalamus.

2) Compare to control group, dexamethasone 0.5mg/kg 3 times pretreatment group(II) showed similar neuronal damage in all areas, although the infaction was focal in striatum and thalamus in group II and generalized in group I. The changes were not statistically significant.

3) Group III showed no significant difference from groups I, II, and IV.

4) Group IV showed more neuronal damage in CA1-2 area of hippocampus compare to groups I and II(p<0.01, p<0.005, respectively).

5) Mortality rate was not significantly different between groups.

In conclusion, dexamethasone pretreatment did not improve hypoxic-ischemic neuronal damage in adult rats. Dexamethasone posttreatment aggravated neuronal damages in CA1-2 area of hippocampus compare to control and pretreatment groups.