The increase of serum Bcl-2 concentration in moderate head injury outcome: The role of ACTH(4-10)Pro(8)-Gly(9)-Pro(10)

BACKGROUND: Traumatic brain injury (TBI) is one of the major causes of death and disability. Apoptosis after TBI contributes significantly to the final extent of tissue damage. The Bcl-2 family proteins are important apoptosis modulators which increased in injured neurons. Bcl-2 has shown an antiapoptotic effect in rats and mice. ACTH(4-10)Pro(8)-Gly(9)-Pro(10) is a synthetic short fragment of ACTH devoid of hormonal effects and has neuromodulatory properties. ACTH(4-10)Pro8-Gly9-Pro10 has been shown to increase levels of Bcl-2 and BDNF in vitro as well as in vivo. It has been postulated that ACTH(4-10)Pro(8)-Gly(9)-Pro(10) will result in improved clinical outcome and reduce hospital length of stay. The goal of this study is to compare the effect of standard therapy only with standard therapy and ACTH(4-10)Pro(8)-Gly(9)-Pro(10), the increase of Bcl-2, and clinical outcome with reduction of hospital stay. MATERIALS AND METHODS: Subjects of moderate head injury (MHI) with no indication of surgery were taken consecutively (n = 40) and separated into two groups: standard treatment only and standard treatment combined with ACTH(4-10)Pro(8)-Gly(9)-Pro(10). Blood samples were taken on day 1 and day 5 from each subject for measurements of Bcl-2 concentration. Barthel Index and MMSE were measured, at discharge and hospital length of stay was noted. RESULTS: Forty subjects have been involved in this study, three subjects died in the standard therapy group, and one subject in ACTH(4-10)Pro(8)-Gly(9)-Pro(10) group. Bcl-2 serum level in standard therapy was 1.39 ± 0.75 ng/mL on day 1 and 1.48 ± 0.77 ng/mL on day 5. After treatment with ACTH(4-10)Pro(8)-Gly(9)-Pro(10), Bcl-2 level was 1.39 ± 0.70 ng/mL on day 1 and 3.70 ± 1.02 ng/mL on day 5. The serum Bcl-2 concentration was significantly increased with ACTH(4-10)Pro(8)-Gly(9)-Pro(10) therapy with shorter hospital length of stay (P < 0.05). CONCLUSION: ACTH(4-10)Pro(8)-Gly(9)-Pro(10) increased serum Bcl-2 levels and reduced hospital length of stay significantly compared with standard therapy alone.