Molecular and histologic outcomes following spinal cord injury in spiny mice, Acomys cahirinus

Abstract

The spiny mouse (Acomys cahirinus) appears to be unique among mammals by showing little scarring or fibrosis after skin or muscle injury, but the Acomys response to spinal cord injury (SCI) is unknown. We tested the hypothesis that Acomys would have molecular and immunohistochemical evidence of reduced spinal inflammation and fibrosis following SCI as compared to C57BL/6 mice (Mus), which similar to all mammals studied to date exhibits spinal scarring following SCI. Initial experiments used two pathway-focused RT-PCR gene arrays (\"wound healing\" and \"neurogenesis\") to evaluate tissue samples from the C2-C6 spinal cord 3-days after a C3/C4 hemi-crush injury (C3Hc). Based on the gene array, specific genes were selected for RT-qPCR evaluation using species-specific primers. The results supported our hypothesis by showing increased inflammation and fibrosis related gene expression (Serpine 1, Plau, Timp1) in Mus as compared to Acomys (P<0.05). RT-qPCR also showed enhanced stem cell and axonal guidance related gene expression (Bmp2, GDNF, Shh) in Acomys compared to Mus (P<0.05). Immunohistochemical evaluation of the spinal lesion at 4-wks post-injury indicated reduced collagen IV immunostaining in Acomys (P<0.05). Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1(IBA1) immunostaining indicated morphological differences in the appearance of astrocytes and macrophages/microglia in Acomys. Collectively, the molecular and histologic results support the hypothesis that Acomys has reduced spinal inflammation and fibrosis following SCI. We suggest that Acomys may be a useful comparative model to study adaptive responses to SCI.\n\nHighlightsO_LISpiny mice (Acomys cahirinus) and C57BL/6 (Mus) were studied after spinal injury\nC_LIO_LIRT-PCR gene arrays suggested different molecular response in Acomys\nC_LIO_LIRTq-PCR with species-specific primers showed increased neurogenesis-related signaling\nC_LIO_LIHistology indicates reduced scarring and fibrosis in Acomys\nC_LIO_LIAcomys may be a useful comparative model to study SCI\nC_LI