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 gro

up

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

<

0.01)

increase of Bax/Bcl-2 ratio (1.91 to 2.40 times) and more TUNEL-positive neurocyte were detected in these above groups. In adult groups only those treated with therapeutic-dose prednisone or corticotrophin for long term displayed above mentioned features.     Conclusion    Excessive apoptosis and initiation of process death are the important mechanism of brain damage induced by prednisone or corticotrophin.