Microenvironment Imbalance of Spinal Cord Injury

Fan, Baoyou; Wei, Zhijian; Yao, Xuemei; Shi, Guidong; Cheng, Xin; Zhou, Xianhu; Zhou, Hengxing; Ning, Guangzhi; Kong, Xiaohong; Feng, Shiqing

doi:10.1177/0963689718755778

Cited by 369 publications

(253 citation statements)

References 153 publications

(177 reference statements)

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“…In contrast, the Mus response is typical of wounding in most mammals, namely the generation of a pro‐inflammatory environment by the production of cytokines secreted by leukocytes, neutrophils, macrophages, microglia, and fibroblasts. These cytokines attract additional blood cells and macrophages to the wound site and can assist with the induction of neurotrophins (Fan et al, ), but excess levels cause scarring (Werner & Grose, ). This self‐reinforcing system can induce fibrosis and subsequent inhibition of axonal regrowth across a spinal lesion.…”

Section: Discussionmentioning

confidence: 99%

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

Streeter

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Brant

et al. 2019

J of Comparative Neurology

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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 results, 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, and Timp1) in Mus as compared to Acomys (p < .05).RT-qPCR also showed enhanced stem cell and axonal guidance related gene expression (Bmp2, GDNF, and Shh) in Acomys compared to Mus (p < .05). Immunohistochemical evaluation of the spinal lesion at 4 weeks postinjury indicated less collagen IV immunostaining in Acomys (p < .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.

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Section: Discussionmentioning

confidence: 99%

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

Streeter

Sunshine

Brant

et al. 2019

J of Comparative Neurology

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show abstract

“…In contrast, the Mus response is typical of wounding in most mammals, namely the generation of a pro-inflammatory environment by the production of cytokines secreted by leukocytes, neutrophils, macrophages, microglia, and fibroblasts. These cytokines attract additional blood cells and macrophages to the wound site and can assist with the induction of neurotrophins (Fan et al, 2018), but excess levels cause scarring (Werner & Grose, 2003). This self-reinforcing system can induce fibrosis and subsequent inhibition of axonal regrowth across a spinal lesion.…”

Section: Discussionmentioning

confidence: 99%

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

Streeter

Sunshine

Brant

et al. 2019

Preprint

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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 3days 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. Highlights• Spiny mice (Acomys cahirinus) and C57BL/6 (Mus) were studied after spinal injury • RT-PCR gene arrays suggested different molecular response in Acomys• RTq-PCR with species-specific primers showed increased neurogenesis-related signaling • Histology indicates reduced scarring and fibrosis in Acomys • Acomys may be a useful comparative model to study SCI

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“…Spinal cord transaction (SCT), a serious damage to nerves which run inside the vertebral column, results in irreversible loss of function at the level and below of injured location, and currently there is no cure [109]. A major reason for the poor prognosis of SCT is associated with neuronal loss and the extremely weak regenerative capacity of axons of the central nervous system after injury; although there is some inherent regenerative capacity of the central nervous system, it is very limited [110]. A recent study revealed the association of eIF5A1 with the neuroplasticity and functional recovery after SCT [111].…”

Section: Neural Diseasesmentioning

confidence: 99%

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

Lau

2020

Cancer Cell Int

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The eukaryotic translation initiation factor 5A1 (eIF5A1) and its homolog eIF5A2 are the only two human proteins containing the unique post-translational modification-hypusination, which is essential for the function of these two proteins. eIF5A1 was initially identified as a translation initiation factor by promoting the first peptide bond formation of protein during translation; however, recent results suggest that eIF5A1 also functions as a translation elongation factor. It has been shown that eIF5A1 is implicated in certain human diseases, including diabetes, several human cancer types, viral infections and diseases of neural system. Meanwhile, eIF5A2 is overexpressed in many cancers, and plays an important role in the development and progression of cancers. As multiple roles of these two factors were observed among these studies, therefore, it remains unclear whether they act as oncogene or tumor suppressor. In this review, the recent literature of eIF5As and their roles in human diseases, especially in human cancers, will be discussed.

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Microenvironment Imbalance of Spinal Cord Injury

Cited by 369 publications

References 153 publications

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

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

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

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

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