Gene Function

Primary Stage

Secondary Stage

Chronic Stage

Repair and regeneration of neurons and glia

Nestin, JAK, STAT, c-fos

Nestin, vimentin, dynamin (–), c-fos

Semaphorin, GAS-7, epithelins 1 and 2, platelet factor 4

Proteins that relay exterior information to the nucleus

PDE, CaM kinases (–)

PDE, MAP kinases, CaM kinases (–)

None

Proteins that generate and maintain cellular structure

None

MOG (–), neurofilaments, LAMP (–), MAP-2, tau (–)

None

Regulation of DNA synthesis

Fra-1, NGFI-A

Fra-1, NGFI-A

None

NOTE: Analysis of proteomic and DNA gene array studies identified significant changes in gene expression in response to a spinal cord injury. Classification of these genes into specific functions provides further insight into the processes that are changing. All genes are up-regulated unless a “(–)” notation is presented, in which case the gene is down-regulated.

SOURCES: Bregman et al., 1997; Segal et al., 1997; Li et al., 2000; Saito et al., 2000; Carmel et al., 2001; Casha et al., 2001; Fan et al., 2001; Song et al., 2001; Zurita et al., 2001; Bareyre et al., 2002; Nesic et al., 2002; Shibuya et al., 2002; Tachibana et al., 2002; Bareyre and Schwab, 2003; Di Giovanni et al., 2003; Dubreuil et al., 2003; Liu et al., 2003; Haberkorn et al., 2004.

whereas 47,000 genes can be represented on a DNA array). Such arrays could be tailored to the specific aspect of spinal cord injury being studied. In addition, advances in mass spectrometry now make it possible to characterize the levels and even the phosphorylation state of many hundreds of proteins, allowing greater insights into the specific activities of proteins.

Issues in Developing Biomarkers for Spinal Cord Injury

It is extremely difficult to obtain samples of mRNA or protein directly from spinal cord tissue without inducing further complications. The most practical sources of mRNA and protein are serum and cerebrospinal fluid.



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