Strokes and other brain injuries can leave their victims permanently disabled due to the death of neurons. Recovery depends on stimulating neurogenesis and neural plasticity. Although the recovery is only partial, most patients undergo some combination of surgery and rehabilitation.

A new study by the Jun Takahashi laboratory shows that this combination has a synergistic effect in rats by promoting outgrowths from the transplanted neurons to recover the neural network lost to the brain damage.

Rehabilitation is a core component to treating many injuries. Many people who have undergone injury to the hand, knee or some other part of the body know that while the surgery may take only a few hours, full recovery occurs only after months of dedicated exercise and training. Brain injuries are no different.

"Cell therapies and rehabilitation alone are normally insufficient, but studies are suggesting their combination improves motor dysfunction. We still do not understand the molecular and cellular effects that cause this synergistic recovery," says CiRA Professor Takahashi, a neurosurgeon.

In the new study, Takahashi's team transplanted brain tissue from embryonic mice into rats that had a portion of their brain removed. The day after the transplantation, the rats began their rehabilitation by running every day for 40 minutes on a treadmill. The transplanted neurons made connections with more regions of the brain in rats that did the rehabilitation than those that did not. This larger network was associated with more neuronal activity. Moreover, rats that ran following the operation showed improved motor skills and faster recovery.

"The success of cell transplantation depends on the ability of the grafted neurons to survive, differentiate, integrate and reconstruct the damaged pathways," says Takahashi.

The study does not identify precisely how rehabilitation enhances the effects of the cell therapy, but previous research has indicated that the rehabilitation promotes the expression of neurotrophic factors that together promote neural growth and plasticity and increased blood flow.

• doi: 10.1038/s41536-019-0075-6