Researchers from the Medical Research Council (MRC) in the UK have found a protein made by blood vessels in the brain that could be a good candidate for regenerative therapies that stimulate the brain to repair itself after injury or disease. They write about their findings in the 9 January online issue of the Proceedings of the National Academy of Sciences.

Although most nerve cells or neurons in the adult brain are made in the womb and soon after birth, they are still produced later on in life, thanks to neural stem cells or NSCs.

NSCs have the potential to specialize into new brain cells, such as in the olfactory bulb, responsible for our sense of smell, and the hippocampus, which plays a key role in forming memories and learning.

NSCs inhabit specialized niches in the adult brain of mammals: these include the subventricular zone and the dentate gyrus, which also control how the stem cells behave.

These niches also contain other cell types, and along with NSCs they are often found next to blood vessels.

The niches generate a range of signals that control how fast the NSCs divide and the types of cell they turn into. Usually these cells become neurons or brain cells that communicate messages, but when the brain suffers an injury like a stroke, more often than not, the NSCs turn into glial cells which become scar tissue.

In this study, the MRC researchers studied the interaction between the cells that line the blood vessels (endothelial cells) and the NSCs, and found that a protein called betacellulin (BTC) boosted brain regeneration in mice by stimulating the NSCs to multiply and form new brain cells.

The researchers found that BTC, which is produced by cells within the blood vessels in the stem cell niches, signals to both the stem cells and to dividing cells called neuroblasts, triggering their proliferation.

When they gave mice more BTC, they noticed a significant increase in both stem cells and neuroblasts, leading to formation of many new neurons in their brains.

But when they gave the mice an antibody that blocks BTC, new neuron production stopped.

Dr Robin Lovell-Badge from the MRC’s National Institute for Medical Research (NIMR), led the study. He said in a statement that we don’t fully understand the function of these stem cell niches in the brain, but it looks as if lots of things have to work together to control what happens to stem cells in the brain.

“We believe these factors are finely balanced to control precisely the numbers of new neurons that are made to match demand in a variety of normal circumstances,” said Lovell-Badge.

“But in trauma or disease, the stem cells either can’t cope with the increased demand, or they prioritise damage control at the expense of long-term repair,” he explained.

Because BTC leads to the production of new neurons rather than glial cells, the researchers hope their findings could help future therapies that aim to regenerate damaged or diseased parts of the brain, such as following stroke, traumatic brain injury, and possibly even in the case of dementia.

However, the work still has a way to go before the learning in the lab translates to therapy in the clinic: more experiments are needed to explain the normal role of BTC, and to explore, with animal studies, what it does on damaged brains, either on its own or together with transplanted NSCs.

Written by Catharine Paddock PhD