Protection of androgen against hypoxic-ischemic brain damage in neonatal rats and possible mechanisms.
OBJECTIVE
Some research has shown that androgen has a neuroprotection against hypoxia-ischemia brain damage (HIBD). However, the relevant mechanism has not been fully elucidated. This study aimed to explore the neuroprotection of androgen against HIBD in neonatal rats and the possible mechanism.


METHODS
Sixty-four seven-day-old Sprague-Dawley (SD) rats were randomly assigned into three groups: Sham-operation, HIBD and Androgen. The HIBD model was induced by ligation of the left carotid common artery along with hypoxia exposure in neonatal rats from the latter two groups. The Sham-operation group was not subjected to hypoxia-ischemia (HI). The Androgen intervention group received an injection of testosterone propionate (25 mg/kg) immediately after HIBD. Bcl-2 and Bax protein expressions in the cortex and hippocampal CA region were detected by immunohistochemical method at 6, 24 and 72 hrs and at 7 days after HI. The contents of SOD and MDA in the brain tissue homogenate were measured by the thiobarbituric acid (TBA) method and the xanthine oxidase luminescence method respectively at 6, 24 and 48 hrs after HI.


RESULTS
There were few Bcl-2 and Bax immune positive cells in the cortex or hippocampus in the left hemisphere in the Sham-operation group at 6 hrs after operation. This was significantly different from the HIBD control and Androgen intervention groups (P < 0.01). The expression of Bcl-2 protein in the cortex and hippocampus of the Androgen intervention group was significantly higher than that of the HIBD control group at 6, 24 and 72 hrs after HI (P < 0.05 or 0.01). The expression of Bax protein in the cortex and hippocampus of the Androgen intervention group was significantly lower than that of the HIBD control group at 24 hrs after HI (P < 0.05). The SOD content in the brain tissue homogenate of the HIBD control group was significantly reduced, in contrast, the MDA content in the brain tissue homogenate of the HIBD control group increased significantly at 6 hrs after HI compared with the Sham-operation group (P < 0.05). The SOD content was reduced to a nadir and the MDA content increased to a peak at 24 hrs after HI in the HIBD control group. Androgen intervention increased significantly the SOD activity at 6,24 and 48 hrs after HI and decreased significantly the MDA content at 6 and 24 hrs after HI as compared with the HIBD control group (P < 0.05 or 0.01).


CONCLUSIONS
The neuroprotection of androgen against neonatal HIBD is produced possibly through an increase of Bcl-2 protein expression and a reduction in Bax protein expression, thus decreasing neuronal apoptosis after HI. There may also be a reduction in the consumption of antioxidant and an inhibition of the formation of oxidant free radicals to alleviate neuronal damage following HI.
Li
Zhan-Kui
ZK
Department of Pediatrics, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, China. lzk@mail.xjtu.edu.cn
Feng
Jin-Xing
JX
Zhao
Chun-Yan
CY
Ke
Hua
H
Shen
Ling
L
D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D043343:Testosterone Propionate / Q000494:pharmacology / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000032:analysis
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D043343:Testosterone Propionate