Pathogenesis of brain damage in infant rats induced by corticosteroids / 第三军医大学学报

ABSTRACT

Objective To explore the possible pathogenesis of brain damage in rats induced by prednisone or corticotrophin. Methods The doses of prednisone or corticotrophin were determined by a primary experiment to obtain corresponding plasma cortisol or corticosterone level as same as that in sick children after drug taking. Then 192 healthy infant (at the age of 7 d) and 192 adult (at the age of 2 months) male SD rats were divided into 4 groups as infant prednisone group, adult prednisone group, infant corticotrophin group and adult corticotrophin group (n=96 in each). then every group was further subdivided into 12 subgroups (n=8 in each). The subgroups were divided according to the dose (therapeutic or low doses), the course [short (10 d) or long (3 weeks)], the sacrificed time (24 h or 4 weeks after withdrawal), and their corresponding controls. Serum neuron-specific enolase (NSE) concentration was quantified by ELISA. Expressions of apoptosis-related proteins, Bax and Bcl-2 in the brain were detected by immunohistochemical assays. Neuronal apoptosis was detected by TUNEL. Results Our primary experiment indicated that the therapeutic dose was 4 mg?kg-1?d-1 or 150 U?m-2?d-1 for prednisone or corticotrophin, and the small dose was 2 mg?kg-1?d-1 or 38 U?m-2?d-1 for them. In infant rats treated with prednisone or corticotrophin at therapeutic-dose for short or long term, their serum NSE concentration were increased significantly by 50.6% to 103.2%. And serum NSE was increased by 38.3% to 60.3% in infant after low-dose treatment for long term. Over-expression of Bax protein (P