Amelioration of Amyotrophic Lateral Sclerosis in SOD1(G93A) Mice by M(2) Microglia from Transplanted Marrow.

Background/Aim: The cause of fatal neuromuscular amyotrophic lateral sclerosis (ALS) is not known. Materials and Methods: Ninety-day-old superoxide-dismutase-1 (G93A) (SOD1 (G93A) ) mice demonstrating level 1 paralysis, received 9.0 Gy total body irradiation (TBI) from a cesium source at 340 cGy per minute, and intravenous transplantation with 1×10 (6) C57BL/6 green fluorescent protein (GFP)+ donor bone marrow cells. Results: Paralysis-free survival was prolonged in TBI and bone marrow-transplanted SOD1 (G93A) mice from 100 to over 250 days (p=0.0018). Other mice transplanted with SOD1 (G93A) marrow or marrow treated with the free-radical scavenger MMS350 showed no therapeutic effect. GFP+ macrophage-2 (M(2)) microglial cells of bone marrow origin, were seen at sites of degenerating anterior horn motor neurons. SOD1 (G93A) mice had a disruption in the blood-brain barrier permeability which was reversed by marrow transplant from C57BL/6 mice. SOD1 (G93A) marrow showed unexpected robust hematopoiesis in vitro, and radioresistance. Conclusion: After TBI, M(2) microglial cells from transplanted donor marrow extended the paralysis-free interval in SOD1 (G93A) mice.