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Neurobiology

Severed Spinal Cord? Not a Problem for Sea Lampreys.

Paper: Hanslik KL, Allen SR, Harkenrider TL, Fogerson SM, Guadarrama E, Morgan JR (2019) Regenerative capacity in the lamprey spinal cord is not altered after a repeated transection. PLoS ONE 14(1): e0204193. https://doi.org/10.1371/journal. pone.0204193

Horseshoe crab blood has helped in detecting endotoxins in vaccines, a bacteria that is quite lethal when injected into human blood. Source: Wikimedia Commons, Pos Robert – U.S. Fish and Wildlife Service.

What if humans could regenerate our body parts? How can amputees or victims of central nervous system (CNS) damage, for example, recover their very own limbs or physical movement? Scientists are hard at work, researching mechanisms that may answer these questions — and they’re drawing inspiration from marine life. From horseshoe crab blood to bioluminescent, deep-sea crustaceans, medicine constantly refers to the wonders of marine adaptation under the sea. Scientists have already learned so much regarding tissue and organ recovery from marine animals like zebrafish, which can regenerate complex organs such as their hearts, and axolotls, which can regenerate entire limbs.

Hello marine Dracula (aka sea lamprey). Credit: NOAA, T. Lawrence – Great Lakes Fishery Commission.

Another marine organism cited for its amazing regenerative capabilities is the lamprey. Sea lampreys are cartilaginous critters inhabiting northern and western Atlantic waters. Unlike many traditional bony fish, these ancient animals do not have any scales, fins, and external gill flaps. However, what lampreys lack in traditional-fish parts, they more than make up for in their special adaptation: their strange, disc-shaped mouth which latches onto prey and sucks out blood. Scientists know that it’s not just the lamprey mouth which makes the organism unique, but also its incredible, rapid regeneration. Research has demonstrated that lampreys can regenerate their spinal cord after it’s been severed, along with their normative physical behaviors.

The natural world has shown successful regeneration for over a century, so the question turns from “can animals regenerate”, to “how well can regenerative capabilities persist after continued or repeated injuries”. Hanslik et al. (2019) test this question by conducting an experiment in which they severed the spinal cords of 5-7 year old, anesthetized sea lampreys, and then severed the same spot again 11 weeks after.*

What Hanslik et al. (2019) found was that, concurrent with previous research, the sea lampreys rapidly regained normative swimming after initial spinal severance. 1 week after the surgery, the lampreys only moved their heads, and were paralyzed below the surgery site. After 3 weeks, the lampreys began swimming again, but displayed certain abnormal movements (such as body contractions). At 11 weeks after the surgery, lampreys regained standard swimming behaviors, comparable to non-injured lampreys. It was after this point when the lampreys underwent surgery to sever their spinal cords in the same spot, and Hanslik et al. (2019) discovered something remarkable: lampreys which had their spinal cords severed twice recovered with a similar speed and trajectory as lampreys which had their spinal cords severed only once. This meant that just 11 weeks after their second spinal severance, lampreys regained typical swimming movements. Not only did Hanslik et al. (2019) see striking similarities in behavioral recovery between lampreys with one spinal severance and lampreys with two, they also noted similarities in tissue growth, axon regeneration, and cell survival.

A: Normal spinal cord appearance. B-D: Severed spinal cord regeneration. E-H: Re-severed spinal cord regeneration. Notice the similarities in recovery time frame, but the slight difference in spinal cord appearance. Source: Hanslik et al. (2019).

Hanslik et al. (2019) do note, however, that while lampreys did recover their normal swimming patterns, their spinal cords did not return back to their original state. Rather, the scientists explain that the lampreys exhibited substantial CNS plasticity: the ability to rewire nervous system connections. Essentially, rather than recovering back to their pre-injured conditions, these spinal cords formed a new network of connections to adapt to an injured state. So while lampreys demonstrated powerful regeneration proceeding both spinal severances, their spinal cords did ultimately recover into a different condition compared to pre-surgery.

Hanslik et al. (2019) take important steps towards understanding the process of repeated regeneration in vertebrates so that we can better understand the obstacles that non-regenerative vertebrates (such as humans) face when dealing with loss of limbs or CNS recovery. As medicine further progresses, scientists like Hanslik et al. (2019) will continue drawing information from marine life and the adaptations that have kept ancient critters, like the 360 million year old sea lamprey, alive. Further work should examine how lampreys regenerate after more than 2 spinal severances, as certain species demonstrate lowered regenerative capabilities after each successive injury, and how these animals recover when different spinal areas responsible for different functioning (sensory functioning, for example) are severed.

* All surgery procedures were approved by the Institutional Animal Care and Use Committee at the Woods Hole Marine Biological Laboratory.

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