Editors' ChoiceSpinal Cord Injury

Sprouting Neurological Function

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Science Translational Medicine  17 Dec 2014:
Vol. 6, Issue 267, pp. 267ec216
DOI: 10.1126/scitranslmed.aaa3461

Injury to the spinal cord, the main information highway up and down the body, triggers upregulation of highly glycosylated proteins at the site of injury. This acts as a barrier to nerve regeneration and “traps” nerves’ growing tips, preventing neurological recovery. Lang et al. developed an inhibitor that interferes with proteoglycan binding to its receptor [protein tyrosine phosphatase σ (PTPσ)] and is able to reverse the nerve regrowth blockage after spinal cord injury and improve the animals’ functional recovery.

Rats with spinal cord injury were injected with the PTPσ-binding drug subcutaneously daily for several weeks. At the end of treatment, urinary function and walking were improved compared with control animals, with higher doses producing better urinary function. Unexpectedly, the researchers did not observe regeneration of corticospinal tract fibers through the injury in the treated rats. Rather, below the lesion, they saw significant sprouting of dense territories of serotonergic neurons. Treatment with a serotonin antagonist reduced locomotor and urinary function in the treatment group but not the control group. This result indicated that the neurological improvement was a result of increased serotonin production from sprouting and regrowth of nerves that survived the injury rather than of reconnections of injured nerve fibers.

The practical advantage of delivering the drug systemically and the positive results of this study suggest that this approach holds great potential as a treatment for patients with spinal cord injury.

B. T. Lang et al., Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury. Nature 10.1038/nature13974 (2014). [Abstract]

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