Rats paralysed by spinal injuries have regained control of their paralysed lower limbs thanks to a combination of movement-provoking drugs and electrical stimulation.
Writing in Science this week, University of Zurich researcher (c) Grays Anatomy (1918)" alt="Vertebral Column" />Gregoire Courtine and his colleagues first induced paralysing injuries in rats by cutting half way across the spinal cord in two places on opposite sides. This injury pattern interrupted the supply of motor nerves from the brain, paralysing the animals' hind limbs.
Control animals followed up for over 2 months showed no recovery of voluntary movement. A further control group of animals placed on a treadmill for half an hour daily, despite making involutary reflex stepping motions, also showed no recovery of volitional movement in the paralysed limbs.
But a third group of animals, treated with a daily regimen of electrical stimulation over the lower spinal cord coupled with injections of neurotransmitter-mimicking drugs called dopamine and 5HT agonists and both treadmill exercises as well as free "overland" reward-incentivised walking, made a remarkable recovery.
Although the animals needed to be supported by a miniature lower-body harness to offset the effects of gravity, within 5 weeks all of the injured rats were walking with a gait indistinguishable from unlesioned animals.
To discover how this was happening, the team traced the patterns of neuronal connections running up and down the spinal cords of the control and recovered animals using markers that label up nerve pathways.
In the control animals, fewer than 2% of the main motor nerves from the brain to the spinal locomotion control centres had survived the cut and very few had regenerated. In contrast, in the electro-chemically rehabilitated rats, the numbers of motor nerve fibres extending below the injury was almost 50%. The surviving nerve fibres, as well as local nerve cells within the spinal cord itself, were branching above the injury site to re-supply the previously disconnected spinal territories on both sides of the cord.
The researchers suggest that the combination of facilitating stimulation as well as "cortical engagement" - giving the animals an incentivised or goal-directed task to restore walking - triggered branching and re-wiring of the surviving connections.
In essence, the animals' nervous system was rewiring itself to bypass the block; this the researchers confirmed by stimulating the motor areas of the animals' brains. In the recovered animals, their muscles took slightly longer to respond, which is consistent with the extra time taken for the signals to negotiate extra synaptic connections to reach the target.
According to Courtine and his team, "these results confirm the capacity of intra-spinal circuits to bypass lesions." The reserachers conclude that their findings might lead to novel interventions capable of improving function in humans with a range of neuromotor disorders.