6-Mercaptopurine attenuates adhesive molecules in experimental vasospasm.

Objective: Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important inflammatory mediators which are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) was effective in preventing and reversing arterial narrowing in a rodent SAH model. The present study was to examine whether levels of adhesion molecules were altered after treatment with 6-mp in this animal model.

Materials And Methods: Animals were each injected with autologous blood into the cisterna magna, and intraperitoneal treatment with 6-mp (2 mg/kg) was initiated 1 h before (prevention) or later (treatment). The compound was subsequently administered at 24 and 48 h post-SAH. Blood samples were collected at 72 h post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. The basilar arteries were harvested and sliced, and their cross-sectional areas were measured. Morphologically, convolution of the internal elastic lamina, distorted endothelial wall, and myonecrosis of the smooth muscle were prominently observed in the SAH only and vehicle-treated SAH groups, but not in the 6-mp-treated SAH group or in healthy controls. No significant differences were found in the levels of VCAM-1 among all groups. However, the levels of E-selectin were increased in all animals subjected to SAH (SAH only and SAH plus vehicle groups) compared with healthy controls (no SAH), but not in the 6-mp group (SAH plus 6-mp treatment and preventive treatment with 6-mp).Likewise, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and pretreatment and treatment with 6-mp reduced ICAM-1 to control levels.

Conclusion: These results show that ICAM-1 and E-selectin may play a role in mediating SAH-induced vasospasm and that a reduction of both adhesive molecules after SAH may partly contribute to the antispastic effect of 6-mp.