People who have suffered traumatic brain injury or stroke often have serious, immediate deficits in motor, sensory, and cognitive function. Interestingly however, these functions often recover in the following weeks and months, without apparent reason. Until now, the repair mechanisms behind this spontaneous recovery have been a mystery. A recent study published in Brain demonstrates the ingenious ability of the central nervous system to repair itself after brain injury.

In anesthetised mice, Ueno and colleagues injured the region of the motor cortex that controls movement of the forelimb, in one hemisphere only. This resulted in the loss of forelimb function on one side, measured by behavioural tests that required the mice to walk across a ladder, up a staircase and through a cylinder. Similar to the spontaneous recovery seen in humans, the mice began to recover their motor function after two weeks, with improvement peaking after six weeks.

To try to understand and visualise the neural processes behind this recovery, the authors injected colored tracers into the injured motor cortex, the same cortical region in the opposite, uninjured hemisphere, and the corticospinal tract, which carries signals from the brain to the limbs to generate movement. This allowed the investigators to look at the changes in the brain and corticospinal tract associated with the loss of motor function and subsequent recovery.

Tracing showed that new fibres, originating in the uninjured motor cortex, began to grow and connect with neurons on the opposite, damaged side of the corticospinal tract. New fibres began to form 2 to 4 weeks after injury, with the new axons growing longer, sprouting “branches”, and finally connecting with the neurons involved in forelimb movement on the damaged side.

It was important to find out if this newly rewired pathway was responsible for the recovery in motor function seen in the mice. The authors stimulated the healthy motor cortex using a microstimulator, and recorded muscle activity in the forelimb on the opposite, injured side. When the healthy cortex was stimulated, the muscles on the injured side responded, demonstrating that this rewiring between the brain and spinal cord was indeed responsible for restoring motor function.

The authors also demonstrate the importance of one molecule, brain-derived neurotrophic factor (BDNF) in this rewiring process. BDNF is important for the growth of neurons throughout the brain, and in this experiment BDNF was necessary to induce sprouting and branching in the new pathways, a process essential for the recovery of function. When BDNF production was blocked, the animals did not recover their motor function.

This study demonstrates that the brain is extremely capable at repairing itself, and suggests exciting new possibilities for improving recovery after traumatic brain injury and stroke in humans. Developing treatments that enhance this rewiring, sprouting and branching process may improve the likelihood of recovery for people who have lost cognitive or motor function due to injury.

References

Ueno M, Hayano Y, Nakagawa H, & Yamashita T (2012). Intraspinal rewiring of the corticospinal tract requires target-derived brain-derived neurotrophic factor and compensates lost function after brain injury. Brain : a journal of neurology, 135 (Pt 4), 1253-67 PMID: 22436236

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