Research ArticleSpinal Cord Injury

Brief Suppression of Abcc8 Prevents Autodestruction of Spinal Cord After Trauma

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Science Translational Medicine  21 Apr 2010:
Vol. 2, Issue 28, pp. 28ra29
DOI: 10.1126/scitranslmed.3000522

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Tackling Spinal Cord Injury

Damage to the brain has a way of spreading. The initial injury often sparks a secondary wave of destruction that enlarges the damaged area and increases the ultimate disability of the patient. This process presents a tempting target for therapeutic intervention and, indeed, numerous agents interfere with secondary injury in brain-damaged animals. But none of these potential drugs have proved effective in humans. Simard and his colleagues now hope to bypass these previous dead ends and successfully interfere with secondary damage by basing their animal work on data taken from human victims of spinal cord injury.

These authors examined brain tissue from seven patients who had died shortly after traumatic injury to the spinal cord and show that one prominent sequel of local damage is that the surrounding tissues show higher than normal concentrations of messenger RNA (mRNA) and protein for the sulfonylurea receptor 1 (SUR1). Their data from rat and mouse show the same thing. This receptor associates with pores in cell membranes to form ion channels, one of which causes cell depolarization and ultimately cell death, creating the wave of secondary damage to the cord. Simard et al. then report that mice in which SUR1 had been genetically removed suffer much less damage to the spinal cord after injury, a result of a less robust wave of spreading damage. Treatment of rats, a better model of human spinal cord injury than mice, with antisense nucleotides that inhibit SUR1 mRNA or with glibenclamide, a nonspecific inhibitor of the whole class of SUR-like proteins, both protected against secondary injury. The capillaries in the cord surrounding the injury were intact rather than fragmented as they are in untreated rats, and the treated rats performed better on a battery of behavioral tests, showing their superior neurological function. Upon later examination, the size of the lesion in the treated animals was only one-quarter the size of the lesion in control animals.

SUR1, therefore, may be a critical element in causing the secondary damage of brain trauma, in humans and rodents. Therapeutic agents that interfere with its injury-induced stimulation of ion channels should be tested in injured patients to determine whether the devastating disability that often results from spinal cord injury can be minimized.


  • Citation: J. M. Simard, S. K. Woo, M. D. Norenberg, C. Tosun, Z. Chen, S. Ivanova, O. Tsymbalyuk, J. Bryan, D. Landsman, V. Gerzanich, Brief Suppression of Abcc8 Prevents Autodestruction of Spinal Cord After Trauma. Sci. Transl. Med. 2, 28ra29 (2010).

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