Abstract
Traumatic spinal cord injury (SCI) results in the formation of a fibrous scar acting as a growth barrier for regenerating axons at the lesion site. We have previously shown (Klapka et al., 2005) that transient suppression of the inhibitory lesion scar in rat spinal cord leads to long distance axon regeneration, retrograde rescue of axotomized cortical motoneurons, and improvement of locomotor function. Here we applied a systemic approach to investigate for the first time specific and dynamic alterations in the cortical gene expression profile following both thoracic SCI and regeneration-promoting anti-scarring treatment (AST). In order to monitor cortical gene expression we carried out microarray analyses using total RNA isolated from layer V/VI of rat sensorimotor cortex at 1–60 days post-operation (dpo). We demonstrate that cortical neurons respond to injury by massive changes in gene expression, starting as early as 1 dpo. AST, in turn, results in profound modifications of the lesion-induced expression profile. The treatment attenuates SCI-triggered transcriptional changes of genes related to inhibition of axon growth and impairment of cell survival, while upregulating the expression of genes associated with axon outgrowth, cell protection, and neural development. Thus, AST not only modifies the local environment impeding spinal cord regeneration by reduction of fibrous scarring in the injured spinal cord, but, in addition, strikingly changes the intrinsic capacity of cortical pyramidal neurons toward enhanced cell maintenance and axonal regeneration.
Highlights
Corticospinal tract (CST) axotomy permanently deprives the motoneurons in layer V of the sensorimotor cortex of their functions in locomotor control
Most studies suggest that central nervous system (CNS) neurons differ in their response to axotomy compared to PNS neurons as exemplified by analyses done on growth-associated protein 43 (Gap43) and α-tubulin (Mikucki and Oblinger, 1991; Tetzlaff et al, 1994; Fournier and McKerracher, 1997)
CST transection we compared the transcriptomes from cortical layer V of anti-scarring treatment (AST)-treated rats to those of sham-operated animals (Figure 1B)
Summary
Corticospinal tract (CST) axotomy permanently deprives the motoneurons in layer V of the sensorimotor cortex of their functions in locomotor control. Possible reasons for regeneration failure of injured axons in the central nervous system (CNS) are the lack of growth-promoting factors (Houweling et al, 1998), the presence of inhibitory cues like the myelin proteins NogoA, myelin-associated glycoprotein (MAG), and oligodendrocytemyelin glycoprotein (OMGP; McKerracher and Winton, 2002; Filbin, 2003), as well as the lesion scar (Fawcett and Asher, 1999; Klapka and Müller, 2006). In addition a recent study revealed no changes in expression of the receptors for myelinassociated inhibitor proteins in any neuronal population of the mouse brain after severe T10 spinal cord contusion (Barrette et al, 2007)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
