Spinal cord injury-induced expression of the antiangiogenic endostatin/collagen XVIII in areas of vascular remodelling.

OBJECT

Spinal cord injury (SCI) induces the disruption of neural and vascular structures. In contrast to the emerging knowledge of mechanisms regulating the onset of the postinjury angiogenic response, little is known about counterregulatory signals.

METHODS

Using immunohistochemical methods, the authors investigated the expression of the endogenous angiogenic inhibitor endostatin/collagen XVIII during the tissue remodeling response to SCI.

RESULTS

After SCI, endostatin/collagen XVIII+ cells accumulated at the lesion site, in pannecrotic regions (especially in areas of cavity formation), at the lesion margin/areas of ongoing secondary damage, and in perivascular Virchow-Robin spaces. In remote areas (> 0.75 cm from the epicenter) a more modest accumulation of endostatin/collagen XVIII+ cells was observed, especially in areas of pronounced Wallerian degeneration. The numbers of endostatin/collagen XVIII+ cells reached their maximum on Day 7 after SCI. The cell numbers remained elevated in both, the lesion and remote regions, compared with control spinal cords for 4 weeks afterwards. In addition to being predominantly confined to ED1+-activated microglia/macrophages within the pannecrotic lesion core, endostatin/collagen XVIII expression was frequently detected by the endothelium/vessel walls. Numbers of lesional endostatin/collagen XVIII+ endothelium/vessel walls were found to increase early by Day 1 postinjury, reaching their maximum on Day 3 and declining subsequently to enhanced (above control) levels 30 days after SCI.

CONCLUSIONS

The authors detected that in comparison to the early expression of neoangiogenic factors, there was a postponed lesional expression of the antiangiogenic endostatin/collagen XVIII. Furthermore, the expression of endostatin/collagen XVIII was localized to areas of neovascular pruning and retraction (cavity formation). The expression of endostatin/collagen XVIII by macrophages in a "late" activated phagocytic mode suggests that this factor plays a role in counteracting the preceding "early" neoangiogenic response after SCI.