Hampton D W, Seitz A, Chen P, Heber-Katz E, Fawcett J W
ICORD, 6270 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z4.
Neuroscience. 2004;127(4):821-32. doi: 10.1016/j.neuroscience.2004.05.057.
The MRL/MpJ mouse has a greatly enhanced healing response and an absence of scarring compared with other mouse strains. Following lesions to the CNS mammals show a scarring response known as reactive gliosis, and this CNS scar tissue blocks regeneration of cut axons. We have therefore compared reactive gliosis in the MRL/MpJ mouse and the Swiss Webster mouse, which exhibits normal scarring in the periphery. The lesion model was a stab lesion to the cortex, in which reactive gliosis has previously been quantified. Axon regeneration was examined following a cut lesion to the dopaminergic projection from the substantia nigra to the striatum used in previous regeneration experiments. In the MRL/MpJ following the lesion compared with Swiss Webster mice there was greater cell loss around the lesion followed by greater and more widespread and more prolonged cellular proliferation. Early after the lesion there was a greater loss of glial fibrillary acidic protein (GFAP)-positive astrocytes around the injury site in the MRL/MpJ, and an enhancement and prolongation of the microglial inflammatory response. This was accompanied by greater and more widespread blood-brain barrier leakage following injury. RNA levels for the matrix metalloproteinases (MMP)-2 and MMP-9 as well as for the thrombin receptors PAR-1 and PAR-4 were also greater at the MRL/MpJ injury site. All of these differences were transient and by 14 days post-injury there were no differences observed between MRL/MpJ and control mice. No axonal regeneration was observed following axotomy to the nigrostriatal pathway of the MRL/MpJ or the Swiss Webster mice at any time point.
与其他小鼠品系相比，MRL/MpJ小鼠具有显著增强的愈合反应且无瘢痕形成。中枢神经系统（CNS）受损后，哺乳动物会出现一种称为反应性胶质增生的瘢痕形成反应，而这种CNS瘢痕组织会阻碍切断轴突的再生。因此，我们比较了MRL/MpJ小鼠和瑞士韦伯斯特小鼠的反应性胶质增生情况，后者在周围组织中表现出正常的瘢痕形成。损伤模型是对皮质进行刺伤，此前已对其中的反应性胶质增生进行了量化。在先前的再生实验中，对从黑质到纹状体的多巴胺能投射进行切断损伤后，检测轴突再生情况。与瑞士韦伯斯特小鼠相比，MRL/MpJ小鼠损伤后，损伤周围的细胞损失更大，随后细胞增殖更强烈、更广泛且更持久。损伤后早期，MRL/MpJ小鼠损伤部位周围胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞的损失更大，小胶质细胞炎症反应增强且持续时间延长。同时，损伤后血脑屏障渗漏更严重且范围更广。基质金属蛋白酶（MMP）-2和MMP-9以及凝血酶受体PAR-1和PAR-4在MRL/MpJ小鼠损伤部位的RNA水平也更高。所有这些差异都是短暂的，损伤后14天时，未观察到MRL/MpJ小鼠与对照小鼠之间存在差异。在任何时间点，对MRL/MpJ小鼠或瑞士韦伯斯特小鼠的黑质纹状体通路进行轴突切断后，均未观察到轴突再生。
