- 作者: Chih-Yen Wang; Jen-Kun Chen, Yi-Ting Wu, May-Jywan Tsai, Song-Kun Shyue, Chung-Shi Yang, Shun-Fen Tzeng
- 作者服務機構: Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment
for tissue repair at the lesion site. To consider an appropriate time window for giving a
promising therapeutic treatment for subacute and chronic SCI, global changes of proteins in
the injured center at the longer survival time points after SCI remains to be elucidated.
Methods: Through two-dimensional electrophoresis (2DE)-based proteome analysis and
western blotting, we examined the differential expression of the soluble proteins isolated
from the lesion center (LC) at day 1 (acute) and day 14 (subacute) after a severe contusive
injury to the thoracic spinal cord at segment 10. In situ apoptotic analysis was used to
examine cell apoptosis in injured spinal cord after adenoviral gene transfer of antioxidant
enzymes. In addition, administration of chondroitinase ABC (chABC) was performed to
analyze hindlimb locomotor recovery in rats with SCI using Basso, Beattie and Bresnahan
(BBB) locomotor rating scale.
Results: Our results showed a decline in catalase (CAT) and Mn-superoxide dismutase
(MnSOD) found at day 14 after SCI. Accordingly, gene transfer of SOD was introduced in
the injured spinal cord and found to attenuate cell apoptosis. Galectin-3, β-actin, actin
regulatory protein (CAPG), and F-actin-capping protein subunit β (CAPZB) at day 14 were
increased when compared to that detected at day 1 after SCI or in sham-operated control.
Indeed, the accumulation of β-actin+ immune cells was observed in the LC at day 14 post SCI, while most of reactive astrocytes were surrounding the lesion center. In addition, chondroitin
sulfate proteoglycans (CSPG)-related proteins with 40-kDa was detected in the LC at day
3-14 post SCI. Delayed treatment with chondroitinase ABC (chABC) at day 3 post SCI
improved the hindlimb locomotion in SCI rats.
Conclusions: Our findings demonstrate that the differential expression in proteins related to
signal transduction, oxidoreduction and stress contribute to extensive inflammation, causing
time-dependent spread of tissue damage after severe SCI. The interventions by supplement of
anti-oxidant enzymes right after SCI or delayed administration with chABC can facilitate
spinal neural cell survival and tissue repair. - 中文關鍵字: --
- 英文關鍵字: --