Can You Repair Brain Cells After They’re Severely Damaged?

Roman Giger in his lab at the University of Michigan Medical School.

Roman Giger 

BrainFacts spoke with Roman Giger, a professor of cell and developmental biology at the University of Michigan Medical School, about what a CNS injury looks like up close and how far we are from a cure. Giger has spent the last quarter of a century studying the molecules that guide how neurons grow during development, and how they might be harnessed to treat people with debilitating neural diseases.

What happens after a severe brain or spinal cord injury?

Let's say, you get a spinal cord injury in a car accident this week. And it’s a severe injury. Many neurons in the brain have long cable-like connections called axons, and the most vulnerable part of the CNS are these connections. So, the cells above the injury and the cells below the injury which receive the signal — they might survive. But the connection is gone.

This injury is immediately followed by all sorts of secondary events like bleeding. It will then result in hypoxia — that means there's not enough blood supply. If cells are damaged, they might release certain chemicals which are toxic. These toxins act on both neurons and glial cells — like oligodendrocytes, astrocytes, and microglia — causing further damage.

Plus, a lot of damage immediately after the injury is actually due to an excessive or prolonged immune response. Immune cells usually remove dead cells and damaged tissue, helping to clean up the injury site and prepare it for healing. When immune cells go out of control, they release harmful molecules that damage DNA, proteins, and cell membranes. They also produce inflammatory signals that promote the death of neurons or limit their ability to regrow. And they release enzymes that break down tissue surrounding the injury, further weakening the protective barrier between the blood and the spinal cord.

Why don’t we regrow those connections?

The nervous system, actually the basic scaffold, develops in embryos. And so even before you’re born, a lot of this wiring — at least the basic scaffold — is in place. There are huge gene families of molecules that tell specific neurons to go here, but not go there.

Once you have the basics, the last step of shaping the network is experience dependent. For example, it takes your eye actually looking at the world to really see properly. There’s a critical period of wiring, and after that it’s pretty much fixed.

The developing brain is like a city under construction — there are plenty of signs that tell nerve fibers where to go. Once the brain is fully built, most of those cues disappear, and after an injury, the environment actually puts up roadblocks that make regrowth very difficult.

How are scientists trying to solve this problem?

There are 3 main approaches.

First, there's an engineering side: In a spinal cord injury, if you can record the electrical signals generated by the neurons in the brain, those signals can be transmitted wirelessly across the injury site to stimulating electrodes placed below the injury in the spinal cord, restoring the lost communication between the brain and the body. It’s a little bit clumsy, but it’s getting better and has delivered some impressive results.

Then there’s stem cells. Instead of regrowing what you have, you basically engineer cells and inject them near the wound to connect the receiver and the sender cells. And if you can get that approximately right, there's probably a good chance you can get some function back. This has been successful, but there's also a lot of questions about safety because these cells might have tumor-like properties.

And then there’s the third camp, which is to basically regrow and heal the damaged tissue. The goal is to repair the injured brain or spinal cord by reactivating natural growth processes active during early development — but largely switched off in adults. These processes allow nerve cells to grow long connections, form new communication points with other nerve cells, and rebuild neural circuits. They also help support cells called oligodendrocytes to produce myelin, the insulating layer that allows electrical signals to travel rapidly along nerve fibers. Scientists hope to reactivate these growth processes using gene editing or drugs that turn specific biological pathways on or off.

This image showcases a tissue section of an adult mouse’s optic nerve. Normally, when axons are injured in the adult optic nerve, they do not regrow beyond injury site (marked by the red asterisk). But after activating specific immune cells in the eye, injured axons (white) were able to regenerate past the injury and extend long distances through the optic nerve. Scale bar = 0.2 mm

Ryan Passino, Giger Lab

But it has to be a holistic approach. Even if you are successful in improving outcomes following CNS injuries, it's probably going to be a tedious, complex combination of therapies, including rehab. Rehab is important because you’ll need to learn and train the network that you rebuild.

However, at the molecular level, many of the mechanisms that help you regenerate one system will be applicable to other injuries or diseases. And I think that's very exciting.