A team of researchers publishing in Aging have shown that resveratrol reduces inflammation and partially restores function in a rat model of spinal injury.
In line with previous research
This is far from the first study that aimed to use approaches associated with aging research in order to spur regeneration. For example, we have previously reported that removing senescent cells aids in spinal cord regeneration in a rodent model, at least partially because of the associated reduction in inflammation.
The researchers cite multiple, related other studies relating to resveratrol and the spinal cord. It reduces inflammation in lung tissues after spinal injury [1], aids in spinal cord regeneration through the mTOR pathway and autophagy [2], protects against spinal cord hypoxic injury through Nrf-2 [3], and aids in spinal regeneration by reducing inflammation through the Notch signaling pathway [4].
However, their study shows a different pathway for the effects of resveratrol: the Wnt/ß-catenin signaling pathway, which plays a significant role in basic cellular maintenance in multiple species.
Motor function restored
Rats that withstand the specific injury used in this experiment normally regain some motor function in their lower bodies according to the widely used Basso, Beattie, Bresnahan (BBB) locomotor scale. However, rats given resveratrol after this injury had BBB scores that were nearly those of uninjured rats after 28 days.
The inclined plane test, on which rats balance on a tilting surface, was also used. Spinally injured rats normally regain only a small amount of balance. This, too, was improved with the use of resveratrol, although not to the level of uninjured rats.
Rats regain very little of their sensory function after this type of injury. Resveratrol was shown to slightly improve this, although not to the level of statistical significance. Taken together, these results appear to show that resveratrol increases the normal regeneration of rats after spinal injury.
Inflammation decreased, regenerative factors increased
Resveratrol significantly decreased the inflammatory factors IL-6, IL-1ß, and TNF-α to approximately half that of untreated injured rats. IL-6 in particular was reduced to the level of uninjured rats.
Spinal injury substantially reduces the levels of GAP43 and NF421, two critical factors involved in nerve regeneration, while increasing GFAP, an astrocyte marker. Resveratrol restored all three of these factors nearly to the levels seen in uninjured rats.
Apoptosis (cellular death) was also measured, both in vitro and in vivo. In both this rat model and a cellular model that used hydrogen peroxide to stimulate apoptosis, resveratrol substantially decreased the rate of apoptosis.
Finally, the researchers examined the expression of multiple Wnt proteins and ß-catenin, whose expression decreases with spinal injury. They found that in rats given resveratrol, the levels of ß-catenin and these Wnt proteins were greatly increased, sometimes well above the levels seen in uninjured rats. GSK-3ß, which increases with spinal injury, was suppressed with resveratrol.
Finally, the researchers set out to prove the role of the Wnt/ß-catenin signaling pathway. They did this by administering XAV939, an inhibitor of this pathway, to a different group of rats that were given resveratrol after injury. As expected, XAV939 partially reversed the effects of resveratrol in both locomotor and biochemical measurements.
Conclusion
This study, along with the studies before it, provides strong evidence that resveratrol helps to restore spinal function through multiple methods. While resveratrol is by no means a cure for spinal injury, its anti-inflammatory and signaling effects make it a clear candidate to be examined as a treatment for spinal injury in humans, possibly alongside stem cell treatments or other therapies that use other approaches to restoring spinal function.
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Literature
[1] Liu, J., Yi, L., Xiang, Z., Zhong, J., Zhang, H., & Sun, T. (2015). Resveratrol attenuates spinal cord injury-induced inflammatory damage in rat lungs. International journal of clinical and experimental pathology, 8(2), 1237.
[2] Meng, H. Y., Shao, D. C., Li, H., Huang, X. D., Yang, G., Xu, B., & Niu, H. Y. (2018). Resveratrol improves neurological outcome and neuroinflammation following spinal cord injury through enhancing autophagy involving the AMPK/mTOR pathway. Molecular medicine reports, 18(2), 2237-2244.
[3] Kesherwani, V., Atif, F., Yousuf, S., & Agrawal, S. K. (2013). Resveratrol protects spinal cord dorsal column from hypoxic injury by activating Nrf-2. Neuroscience, 241, 80-88.
[4] Zhang, S., Botchway, B. O., Zhang, Y., & Liu, X. (2019). Resveratrol can inhibit Notch signaling pathway to improve spinal cord injury. Annals of Anatomy-Anatomischer Anzeiger, 223, 100-107.
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