Angiogenesis and Neurogenesis in chronic cerebral hypoperfusion or treated with EMAS model in rat

초록

Objective : Moyamoya disease is charaterized by a rare and chronic cerebral hypoperfusion condition which pogressively induced stenosis of the internal carotid artery and its distal arteries. Various direct or indirect vasoreconstructive surgical protocols have been carried out but with moderate success rate. We evaluated whether the indirect vasoreconstructive surgery, by itself or combined with an administration of granulocyte macrophage-colony stimulating factor (GM-CSF), enhances brain angiogenesis and modulate angiogenic factors in a chronic cerebral hypoperfusion model in rats. Methods : Male SD rats (6 weeks) were divided into 4 groups (sham, injury, injury+EMAS, injury+EMAS+GM-CSF). Brain hypoperfusion injury was performed by occlusion of bilateral internal carotid artery. After 1 week, the EMAS groups received craniectomy and the exposed brain surface was covered with the muscle flap isolated from the temporal bone. GM-CSF was treated intraperitoneally at 20 mg/ml for 5 days. All rats received intraperitenial injection of BrdU (50mg/Kg/day) for 5 days consecutively. The animals were sacrificed 3 weeks post-injury then analyzed by immunohistochemistry and Western blot for angiogenesis and neurogenesis. Results : There were significant increase in the number of vessels and BrdU positive cells in the EMAS and EMAS+GM-CSF groups compared with those of 2 VO group. The BrdU positive cells were mostly expressed in neurons (NeuN) but not astrocytes (GFAP). There was also increase in the expression of angiogenic factors in the EMAS and EMAS+GM-CSF groups compared with the 2 VO group. Conclusion : EMAS may be an effective surgical method for moyamoya disease and will be more effective if combined with administration of GM-CSF.