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Updated: Aug 15, 2026
Mouse Models of Periventricular Leukomalacia
Published on: May 18, 2010
Altered CNS response to injury in the MRL/MpJ mouse
1ICORD, 6270 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z4. dhampton@icord.org
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.
Insights
The MRL/MpJ mouse shows enhanced healing and reduced scarring after central nervous system (CNS) lesions. However, this strain did not regenerate axons, indicating scarring does not solely impede CNS repair.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Immunology
Background:
- Mammalian central nervous system (CNS) repair is hindered by scarring, specifically reactive gliosis.
- The MRL/MpJ mouse strain exhibits superior wound healing and minimal scarring compared to other strains.
- Understanding scar formation differences could reveal new therapeutic targets for CNS regeneration.
Purpose of the Study:
- To compare reactive gliosis and scarring responses in MRL/MpJ mice versus Swiss Webster mice following CNS lesions.
- To investigate the potential for axonal regeneration in the MRL/MpJ mouse model.
- To identify molecular differences contributing to scar formation and healing.
Main Methods:
- Inducing stab lesions in the cortex and axotomy of the nigrostriatal pathway in MRL/MpJ and Swiss Webster mice.
- Quantifying reactive gliosis, including glial fibrillary acidic protein (GFAP)-positive astrocytes and microglial response.
- Measuring blood-brain barrier permeability and gene expression of matrix metalloproteinases (MMPs) and thrombin receptors.
Main Results:
- MRL/MpJ mice displayed greater initial cell loss, proliferation, and prolonged inflammatory response post-lesion.
- Enhanced blood-brain barrier leakage and elevated MMP and thrombin receptor RNA levels were observed in MRL/MpJ mice.
- Despite initial differences, scar formation and cellular responses normalized by 14 days post-injury in MRL/MpJ mice.
- No axonal regeneration was observed in either mouse strain following nigrostriatal pathway axotomy.
Conclusions:
- The MRL/MpJ mouse's enhanced healing response involves a transient, exaggerated inflammatory and cellular proliferation phase.
- Scarring, while modified, does not appear to be the sole factor preventing axonal regeneration in this CNS injury model.
- Further research is needed to understand the mechanisms underlying the MRL/MpJ mouse's unique healing characteristics and their implications for CNS repair.
