Altered CNS response to injury in the MRL/MpJ mouse

Abstract

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.