A study published in the January 9 issue of Science has brought hope for the treatment of paralysis due to spinal cord injury.

Damage to the spinal cord can cut communication between the brain and the peripheral nervous system. To restore communication, some strategies have been tested over the years. Research has been working on developing spinal implants that may electrically stimulate the spinal cord while also acting as delivery media for molecules able to promote axonal regeneration.

The good news

Wire implants have been tested, but they have failed mainly due to their rigidity. Movements of the spine can damage or break these electrodes and these strategies end up failing quite quickly.

But a Swiss group developed a strategy to overcome these limitations. They developed a soft neural implant that can be placed in contact with nerve tissue, with the shape and elasticity of dura mater, the membrane that envelops the spinal cord. This electronic dura mater, which the authors called e-dura, consists of a ribbon of stretchable silicone that can send signals along the nerves because it’s embedded with gold wires that can conduct neuronal signals. Its softness is maintained by fracturing the gold wires with micro-cracks, allowing them to bend with the silicone.

Additionally, it contains fluid channels that allow the delivery of drugs to nerve cells. This allows the controlled release of regeneration stimulating factors, such as molecules that actively promote axonal extension. Importantly, it allows a localized delivery of these factors, thereby reducing potential side-effects.

The authors tested this implant by placing it into the injured spinal cords of paralyzed rats. They tested the therapeutic effects of the e-dura by using the implant to stimulate the spinal cord with electrical signals as well as with molecules that improve nerve impulse transmission. This approach was able to restore the rats’ ability to walk only after six weeks. The success of this implant in animals is quite promising and may be an important step towards helping paralyzed patients regain their ability to walk.

The bad news

Stroke has widely known consequences in neurological function. Infections are common post-stroke complications, especially pneumonia. Post-stroke infections are associated with increased mortality and poor neurological outcomes. Prophylactic antibiotic treatment has been shown to reduce the frequency of post-stroke infections. However, whether or not preventive antibiotic treatment reduces the risk of poor functional outcome after stroke has been uncertain.

A study made available online on January 20 in The Lancet aimed to determine whether or not preventive antimicrobial therapy could improve neurological functional outcome in patients with acute stroke. The Preventive Antibiotics in Stroke Study (PASS) was a multicentre randomized controlled trial with 2550 patients from 30 centers in the Netherlands undertaken between 2010 and 2014. Patients were assigned in a 1:1 ratio to either preventive antibiotic therapy or a control group and the three-month functional outcome was determined. Ceftriaxone, a broad-spectrum third-generation cephalosporin antibiotic that is often used to treat post-stroke infections was chosen for this study.

Preventive antibiotic therapy was unable to improve functional outcomes in patients with acute stroke, shorten the length of hospital stay or reduce mortality. Although post-stroke infection rate was significantly reduced with Ceftriaxone, pneumonia was not prevented. Since pneumonia was strongly associated with an unfavorable neurological outcome, the lack of functional effect of ceftriaxone may have been due to its inability to prevent post-stroke pneumonia. The authors hypothesize that pneumonia may actually be a post-stroke respiratory syndrome, rather than solely a bacterial infection.

The results of this trial do not support the use of preventive antibiotics in adults with acute stroke. This is a problem that remains unsolved.

References

Minev IR, Musienko P, Hirsch A, Barraud Q, Wenger N, Moraud EM, Gandar J, Capogrosso M, Milekovic T, Asboth L, Torres RF, Vachicouras N, Liu Q, Pavlova N, Duis S, Larmagnac A, Vörös J, Micera S, Suo Z, Courtine G, & Lacour SP (2015). Biomaterials. Electronic dura mater for long-term multimodal neural interfaces. Science (New York, N.Y.), 347 (6218), 159-63 PMID: 25574019

Westendorp WF, Vermeij JD, Zock E, Hooijenga IJ, Kruyt ND, Bosboom HJ, Kwa VI, Weisfelt M, Remmers MJ, Ten Houten R, Schreuder AH, Vermeer SE, van Dijk EJ, Dippel DW, Dijkgraaf MG, Spanjaard L, Vermeulen M, van der Poll T, Prins JM, Vermeij FH, Roos YB, Kleyweg RP, Kerkhoff H, Brouwer MC, Zwinderman AH, van de Beek D, Nederkoorn PJ, & for the PASS investigators (2015). The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial. Lancet PMID: 25612858

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