Microglia/macrophages play important functional roles in regeneration after central nervous system injury. Infiltration of circulating macrophages and proliferation of resident microglia occur within minutes following spinal cord injury. Activated microglia/macrophages clear tissue debris, but activation over time may hamper repair. To study the role of these cells in regeneration after spinal cord injury we used CD11b-herpes simplex virus thymidine kinase (HSVTK) (TK) transgenic mice, in which viral thymidine kinase activates ganciclovir toxicity in CD11b-expressing myeloid cells, including macrophages and microglia. A severe reduction in number of these cells was seen in TK versus wild-type littermate mice at 1 week and 5 weeks after injury, and numbers of Mac-2 expressing activated microglia/macrophages were almost completely reduced at these time points. One week after injury TK mice showed better locomotor recovery, but recovery was similar to wild-type mice as measured weekly up to 5 weeks thereafter. At 5 weeks after injury, numbers of axons at the lesion site and neurons in the lumbar spinal cord did not differ between groups. Also, catecholaminergic innervation of spinal motoneurons was similar. However, cholinergic innervation was lower and glial scarring was increased in TK mice compared to wild-type mice. We conclude that reducing numbers of CD11b-expressing cells improves locomotor recovery in the early phase after spinal cord injury, but does not affect recovery in the following 4 weeks. These observations point to differences in outcomes of astrocytic response and cholinergic innervation under CD11b cell ablation, which are, however, not reflected in the locomotor parameters analyzed at 5 weeks after injury.

小胶质细胞/巨噬细胞在中枢神经系统损伤后的再生中起重要的功能作用。脊髓损伤后数分钟内发生循环巨噬细胞浸润和常驻小胶质细胞增殖。活化的小胶质细胞/巨噬细胞清除组织碎片，但随着时间的推移活化可能会妨碍修复。为了研究这些细胞在脊髓损伤后再生中的作用，我们使用了CD11b-单纯疱疹病毒胸苷激酶（HSVTK）（TK）转基因小鼠，其中病毒胸苷激酶激活了表达CD11b的髓样细胞（包括巨噬细胞和小胶质细胞）中的更昔洛韦毒性。与野生型同窝小鼠相比，TK在损伤后1周和5周时这些细胞的数量大大减少，在这些时间点，表达Mac-2的活化小胶质细胞/巨噬细胞的数量几乎完全减少。受伤后一星期TK小鼠表现出更好的运动恢复，但恢复至与野生型小鼠相似，直到其后5周每周进行一次测量。损伤后5周，两组之间病变部位的轴突和腰脊髓神经元的数量没有差异。同样，脊髓运动神经元的儿茶酚胺能神经支配是相似的。但是，与野生型小鼠相比，TK小鼠的胆碱能神经支配较低，神经胶质瘢痕形成增加。我们得出的结论是，减少CD11b表达细胞的数量可改善脊髓损伤后早期的运动恢复，但不会影响随后4周的恢复。